Quantitative Predictions of Binding Free Energy Changes in Drug-Resistant Influenza Neuraminidase

DTIC Science & Technology

2012-08-30

drug resistance to two antiviral drugs, zanamivir and oseltamivir. We augmented molecular dynamics (MD) with Hamiltonian Replica Exchange and...conformations that are virtually identical to WT [10]. Molecular simulations that rigorously model the microscopic structure and thermodynamics PLOS...influenza neuraminidase (NA) that confer drug resistance to two antiviral drugs, zanamivir and oseltamivir. We augmented molecular dynamics (MD) with

Effect of progressive resistance exercise with neuromuscular joint facilitation on the dynamic balance performance of junior soccer players.

PubMed

Wang, Hongzhao; Huo, Ming; Guan, Peipei; Onoda, Ko; Chen, Di; Huang, Qiuchen; Maruyama, Hitoshi

2015-11-01

[Purpose] The aim of this study was to investigate the change in dynamic balance performance of junior soccer players after progressive resistance treatment with neuromuscular joint facilitation (NJF). [Subjects] The subjects were 14 healthy males who were divided into two groups, namely the NJF and control groups. The NJF group consisted of 8 subjects, and the control group consisted of 6 subjects. [Methods] The participants in the NJF group received NJF progressive resistance treatment. Dynamic balance performance was measured before and after 3 weeks of exercise. [Results] Significant improvement in dynamic balance performance was observed both in the NJF and control groups. In the NJF group, dynamic balance performance was significantly increased compared with that in the control group. [Conclusion] The NJF intervention shortened movement time, which implies that NJF is effective for dynamic balance performance.

Exercise Training for Blood Pressure: A Systematic Review and Meta‐analysis

PubMed Central

Cornelissen, Veronique A.; Smart, Neil A.

2013-01-01

Background We conducted meta‐analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes. Methods and Results Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer‐reviewed journal up to February 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (SBP) was reduced after endurance (−3.5 mm Hg [confidence limits −4.6 to −2.3]), dynamic resistance (−1.8 mm Hg [−3.7 to −0.011]), and isometric resistance (−10.9 mm Hg [−14.5 to −7.4]) but not after combined training. Reductions in diastolic BP (DBP) were observed after endurance (−2.5 mm Hg [−3.2 to −1.7]), dynamic resistance (−3.2 mm Hg [−4.5 to −2.0]), isometric resistance (−6.2 mm Hg [−10.3 to −2.0]), and combined (−2.2 mm Hg [−3.9 to −0.48]) training. BP reductions after endurance training were greater (P<0.0001) in 26 study groups of hypertensive subjects (−8.3 [−10.7 to −6.0]/−5.2 [−6.8 to −3.4] mm Hg) than in 50 groups of prehypertensive subjects (−2.1 [−3.3 to −0.83]/−1.7 [−2.7 to −0.68]) and 29 groups of subjects with normal BP levels (−0.75 [−2.2 to +0.69]/−1.1 [−2.2 to −0.068]). BP reductions after dynamic resistance training were largest for prehypertensive participants (−4.0 [−7.4 to −0.5]/−3.8 [−5.7 to −1.9] mm Hg) compared with patients with hypertension or normal BP. Conclusion Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in SBP. PMID:23525435

Current perspectives on the dynamics of antibiotic resistance in different reservoirs.

PubMed

Caniça, Manuela; Manageiro, Vera; Jones-Dias, Daniela; Clemente, Lurdes; Gomes-Neves, Eduarda; Poeta, Patrícia; Dias, Elsa; Ferreira, Eugénia

2015-09-01

Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate among relevant reservoirs (human, animal, and environmental settings), evaluating how these events contribute to the current scenario of antibiotic resistance. The relationship between the spread of resistance and the contribution of different genetic elements and events is revisited, exploring examples of the processes by which successful mobile resistance genes spread across different niches. The importance of classic and next generation molecular approaches, as well as action plans and policies which might aid in the fight against antibiotic resistance, are also reviewed. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Solid-Liquid Interface Thermal Resistance Affects the Evaporation Rate of Droplets from a Surface: A Study of Perfluorohexane on Chromium Using Molecular Dynamics and Continuum Theory.

PubMed

Han, Haoxue; Schlawitschek, Christiane; Katyal, Naman; Stephan, Peter; Gambaryan-Roisman, Tatiana; Leroy, Frédéric; Müller-Plathe, Florian

2017-05-30

We study the role of solid-liquid interface thermal resistance (Kapitza resistance) on the evaporation rate of droplets on a heated surface by using a multiscale combination of molecular dynamics (MD) simulations and analytical continuum theory. We parametrize the nonbonded interaction potential between perfluorohexane (C 6 F 14 ) and a face-centered-cubic solid surface to reproduce the experimental wetting behavior of C 6 F 14 on black chromium through the solid-liquid work of adhesion (quantity directly related to the wetting angle). The thermal conductances between C 6 F 14 and (100) and (111) solid substrates are evaluated by a nonequilibrium molecular dynamics approach for a liquid pressure lower than 2 MPa. Finally, we examine the influence of the Kapitza resistance on evaporation of droplets in the vicinity of a three-phase contact line with continuum theory, where the thermal resistance of liquid layer is comparable with the Kapitza resistance. We determine the thermodynamic conditions under which the Kapitza resistance plays an important role in correctly predicting the evaporation heat flux.

Electrical resistivity and thermal conductivity of liquid aluminum in the two-temperature state

NASA Astrophysics Data System (ADS)

Petrov, Yu V.; Inogamov, N. A.; Mokshin, A. V.; Galimzyanov, B. N.

2018-01-01

The electrical resistivity and thermal conductivity of liquid aluminum in the two-temperature state is calculated by using the relaxation time approach and structural factor of ions obtained by molecular dynamics simulation. Resistivity witin the Ziman-Evans approach is also considered to be higher than in the approach with previously calculated conductivity via the relaxation time. Calculations based on the construction of the ion structural factor through the classical molecular dynamics and kinetic equation for electrons are more economical in terms of computing resources and give results close to the Kubo-Greenwood with the quantum molecular dynamics calculations.

The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.

PubMed

Trauner, Andrej; Liu, Qingyun; Via, Laura E; Liu, Xin; Ruan, Xianglin; Liang, Lili; Shi, Huimin; Chen, Ying; Wang, Ziling; Liang, Ruixia; Zhang, Wei; Wei, Wang; Gao, Jingcai; Sun, Gang; Brites, Daniela; England, Kathleen; Zhang, Guolong; Gagneux, Sebastien; Barry, Clifton E; Gao, Qian

2017-04-19

Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics. By combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance. Our findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.

Development and evaluation of pile "high strain dynamic test database" to improve driven capacity estimates : phase 1 report.

DOT National Transportation Integrated Search

2014-01-01

The Maine Department of Transportation (MaineDOT) has noted poor correlation between predicted pile resistances : calculated using commonly accepted design methods and measured pile resistance from dynamic pile load tests (also : referred to as high ...

Development and evaluation of pile "high strain dynamic test database" to improve driven capacity estimates : phase 2 report.

DOT National Transportation Integrated Search

2014-01-01

The Maine Department of Transportation (MaineDOT) has noted poor correlation between predicted pile resistances : calculated using commonly accepted design methods and measured pile resistance from dynamic pile load tests (also : referred to as high ...

Quasispecies dynamics and the emergence of drug resistance during zidovudine therapy of HIV infection.

PubMed

Frost, S D; McLean, A R

1994-03-01

To investigate the roles of mutation, competition and population dynamics in the emergence of drug resistant mutants during zidovudine therapy. A mathematical model of the population dynamics of the viral quasispecies during zidovudine therapy was investigated. The model was used to simulate changes in the numbers of uninfected and infected cells and the composition of the viral quasispecies in the years following initiation of therapy. Resulting scenarios in asymptomatic and AIDS patients were compared. The model was also used to investigate the efficacy of a treatment regimen involving alternating zidovudine and dideoxyinosine therapy. The behaviour of the model can be divided into three stages. Before therapy, mutation maintains a small pool of resistant mutants, outcompeted to very low levels by sensitive strains. When therapy begins there is a dramatic fall in the total viral load and resistant strains suddenly have the competitive advantage. Thus, it is resistant strains that infect the rising number of uninfected CD4+ cells. During this second stage the rapid effects of population dynamics swamp any effects of mutation between strains. When the populations of infected and uninfected cells approach their treatment equilibrium levels, mutation again becomes important in the slow generation of highly resistant strains. The short-term reduction in viral replication at the initiation of therapy generates a pool of uninfected cells which cause the eventual increase in viral burden. This increase is associated with (but not caused by) a rise in frequency of resistant strains which are at a competitive advantage in the presence of the drug. When therapy is ceased, reversion of resistance is slow as resistant strains are nearly as fit as sensitive strains in the absence of drug.

Acute effects of a resisted dynamic warm-up protocol on jumping performance.

PubMed

Cilli, M; Gelen, E; Yildiz, S; Saglam, T; Camur, Mh

2014-12-01

This study aimed to investigate the kinematic and kinetic changes when resistance is applied in horizontal and vertical directions, produced by using different percentages of body weight, caused by jumping movements during a dynamic warm-up. The group of subjects consisted of 35 voluntary male athletes (19 basketball and 16 volleyball players; age: 23.4 ± 1.4 years, training experience: 9.6 ± 2.7 years; height: 177.2 ± 5.7 cm, body weight: 69.9 ± 6.9 kg) studying Physical Education, who had a jump training background and who were training for 2 hours, on 4 days in a week. A dynamic warm-up protocol containing seven specific resistance movements with specific resistance corresponding to different percentages of body weight (2%, 4%, 6%, 8%, 10%) was applied randomly on non consecutive days. Effects of different warm-up protocols were assessed by pre-/post- exercise changes in jump height in the countermovement jump (CMJ) and the squat jump (SJ) measured using a force platform and changes in hip and knee joint angles at the end of the eccentric phase measured using a video camera. A significant increase in jump height was observed in the dynamic resistance warm-up conducted with different percentages of body weight (p < 0.05). On the other hand, no significant difference in different percentages of body weight states was observed (p > 0.05). In jump movements before and after the warm-up, while no significant difference between the vertical ground reaction forces applied by athletes was observed (p > 0.05), in some cases of resistance, a significant reduction was observed in hip and knee joint angles (p < 0.05). The dynamic resistance warm-up method was found to cause changes in the kinematics of jumping movements, as well as an increase in jump height values. As a result, dynamic warm-up exercises could be applicable in cases of resistance corresponding to 6-10% of body weight applied in horizontal and vertical directions in order to increase the jump performance acutely.

ACUTE EFFECTS OF A RESISTED DYNAMIC WARM-UP PROTOCOL ON JUMPING PERFORMANCE

PubMed Central

Cilli, M; Yildiz, S; Saglam, T; Camur, MH

2014-01-01

This study aimed to investigate the kinematic and kinetic changes when resistance is applied in horizontal and vertical directions, produced by using different percentages of body weight, caused by jumping movements during a dynamic warm-up. The group of subjects consisted of 35 voluntary male athletes (19 basketball and 16 volleyball players; age: 23.4 ± 1.4 years, training experience: 9.6 ± 2.7 years; height: 177.2 ± 5.7 cm, body weight: 69.9 ± 6.9 kg) studying Physical Education, who had a jump training background and who were training for 2 hours, on 4 days in a week. A dynamic warm-up protocol containing seven specific resistance movements with specific resistance corresponding to different percentages of body weight (2%, 4%, 6%, 8%, 10%) was applied randomly on non consecutive days. Effects of different warm-up protocols were assessed by pre-/post- exercise changes in jump height in the countermovement jump (CMJ) and the squat jump (SJ) measured using a force platform and changes in hip and knee joint angles at the end of the eccentric phase measured using a video camera. A significant increase in jump height was observed in the dynamic resistance warm-up conducted with different percentages of body weight (p < 0.05). On the other hand, no significant difference in different percentages of body weight states was observed (p > 0.05). In jump movements before and after the warm-up, while no significant difference between the vertical ground reaction forces applied by athletes was observed (p > 0.05), in some cases of resistance, a significant reduction was observed in hip and knee joint angles (p < 0.05). The dynamic resistance warm-up method was found to cause changes in the kinematics of jumping movements, as well as an increase in jump height values. As a result, dynamic warm-up exercises could be applicable in cases of resistance corresponding to 6-10% of body weight applied in horizontal and vertical directions in order to increase the jump performance acutely. PMID:25435670

Dynamics of Preferential Substrate Recognition in HIV-1 Protease: Redefining the Substrate Envelope

PubMed Central

Özen, Ayşegül; Haliloğlu, Türkan; Schiffer, Celia A.

2011-01-01

HIV-1 protease (PR) permits viral maturation by processing the Gag and Gag-Pro-Pol polyproteins. Though HIV-1 PR inhibitors (PIs) are used in combination antiviral therapy, the emergence of drug resistance has limited their efficacy. The rapid evolution of HIV-1 necessitates the consideration of drug resistance in novel drug-design strategies. Drug-resistant HIV-1 PR variants, while no longer efficiently inhibited, continue to efficiently hydrolyze the natural viral substrates. Though highly diverse in sequence, the HIV-1 PR substrates bind in a conserved three-dimensional shape we defined as the “substrate envelope”. We previously showed that resistance mutations arise where PIs protrude beyond the substrate envelope, as these regions are crucial for drug binding but not for substrate recognition. Here, we extend this model by considering the role of protein dynamics in the interaction of HIV-1 PR with its substrates. Seven molecular dynamics simulations of PR-substrate complexes were performed to estimate the conformational flexibility of substrates in their complexes. Interdependency of the substrate-protease interactions may compensate for the variations in cleavage-site sequences, and explain how a diverse set of sequences can be recognized as substrates by the same enzyme. This diversity may be essential for regulating sequential processing of substrates. We also define a dynamic substrate envelope as a more accurate representation of PR-substrate interactions. This dynamic substrate envelope, described by a probability distribution function, is a powerful tool for drug design efforts targeting ensembles of resistant HIV-1 PR variants with the aim of developing drugs that are less susceptible to resistance. PMID:21762811

Drug resistance conferred by mutations outside the active site through alterations in the dynamic and structural ensemble of HIV-1 protease.

PubMed

Ragland, Debra A; Nalivaika, Ellen A; Nalam, Madhavi N L; Prachanronarong, Kristina L; Cao, Hong; Bandaranayake, Rajintha M; Cai, Yufeng; Kurt-Yilmaz, Nese; Schiffer, Celia A

2014-08-27

HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination of mutations occur both inside and outside the protease active site. With few exceptions, the role of mutations outside the active site in conferring resistance remains largely elusive. Through a series of DRV-protease complex crystal structures, inhibition assays, and molecular dynamics simulations, we find that single and double site mutations outside the active site often associated with DRV resistance alter the structure and dynamic ensemble of HIV-1 protease active site. These alterations correlate with the observed inhibitor binding affinities for the mutants, and suggest a network hypothesis on how the effect of distal mutations are propagated to pivotal residues at the active site and may contribute to conferring drug resistance.

Testing the dynamic rollover resistance of two 15-passenger vans with multiple load configurations

DOT National Transportation Integrated Search

2004-06-01

As a consequence of NTSB Safety Recommendations H-02-26 and H-02-28, NHTSA performed a study to investigate the effects different load conditions may have on the dynamic rollover resistance of 15-passenger vans. The two vans used in this study, a 200...

An advanced arc track resistant airframe wire

NASA Technical Reports Server (NTRS)

Beatty, J.

1995-01-01

Tensolite, a custom cable manufacturer specializing in high temperature materials as the dielectric medium, develops an advance arc track resistant airframe wire called Tufflite 2000. Tufflite 2000 has the following advantages over the other traditional wires: lighter weight and smaller in diameter; excellent wet and dry arc track resistance; superior dynamic cut-through performance even at elevated temperatures; flight proven performance on Boeing 737 and 757 airplanes; and true 260 C performance by utilizing Nickel plated copper conductors. This paper reports the different tests performed on Tufflite 2000: accelerated aging, arc resistance (wet and dry), dynamic cut through, humidity resistance, wire-to-wire abrasion, flammability, smoke, weight, notch sensitivity, flexibility, and markability. It particularly focuses on the BSI (British Standards Institute) dry arc resistance test and BSI wet arc tracking.

Proposed Assessment of Dynamic Resistance of the Existing Industrial Portal Frame Building Structures to the Impact of Mining Tremors

NASA Astrophysics Data System (ADS)

Rusek, Janusz; Kocot, Wojciech

2017-10-01

The article presents the method for assessing dynamic resistance of the existing industrial portal frame building structures subjected to mining tremors. The study was performed on two industrial halls of a reinforced concrete structure and a steel structure. In order to determine the dynamic resistances of these objects, static and dynamic numerical analysis in the FEA environment was carried out. The scope of numerical calculations was adapted to the guidelines contained in the former and current design standards. This allowed to formulate the criteria, on the basis of which the maximum permissible value of the horizontal ground acceleration was obtained, constituting resistance of the analyzed objects. The permissible range of structural behaviour was determined by comparing the effects of load combinations adopted at the design stage with a seismic combination recognized in Eurocode 8. The response spectrum method was used in the field of dynamic analysis, taking into account the guidelines contained in Eurocode 8 and the guidelines of National. Finally, in accordance with the established procedure, calculations were carried out and the results for the two model portal frame buildings of reinforced concrete and steel structures were presented. The results allowed for the comparison of the dynamic resistance of two different types of material and design, and a sensitivity analysis with respect to their constituent bearing elements. The conclusions drawn from these analyses helped to formulate the thesis for the next stage of the research, in which it is expected to analyze a greater number of objects using a parametric approach, in relation to the geometry and material properties.

Bacterial Cheating Limits the Evolution of Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Yurtsev, Eugene; Xiao Chao, Hui; Datta, Manoshi; Artemova, Tatiana; Gore, Jeff

2012-02-01

The emergence of antibiotic resistance in bacteria is a significant health concern. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removal of the antibiotic. The presence of a cooperative mechanism of resistance suggests that a cheater strain - which does not contribute to breaking down the antibiotic - may be able to take advantage of resistant cells. We find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We use a simple model in conjunction with difference equations to explain the observed population dynamics as a function of cell density and antibiotic concentration. Our experimental difference equations resemble the logistic map, raising the possibility of oscillations or even chaotic dynamics.

Nanoscale inhomogeneity and photoacid generation dynamics in extreme ultraviolet resist materials

NASA Astrophysics Data System (ADS)

Wu, Ping-Jui; Wang, Yu-Fu; Chen, Wei-Chi; Wang, Chien-Wei; Cheng, Joy; Chang, Vencent; Chang, Ching-Yu; Lin, John; Cheng, Yuan-Chung

2018-03-01

The development of extreme ultraviolet (EUV) lithography towards the 22 nm node and beyond depends critically on the availability of resist materials that meet stringent control requirements in resolution, line edge roughness, and sensitivity. However, the molecular mechanisms that govern the structure-function relationships in current EUV resist systems are not well understood. In particular, the nanoscale structures of the polymer base and the distributions of photoacid generators (PAGs) should play a critical roles in the performance of a resist system, yet currently available models for photochemical reactions in EUV resist systems are exclusively based on homogeneous bulk models that ignore molecular-level details of solid resist films. In this work, we investigate how microscopic molecular organizations in EUV resist affect photoacid generations in a bottom-up approach that describes structure-dependent electron-transfer dynamics in a solid film model. To this end, molecular dynamics simulations and stimulated annealing are used to obtain structures of a large simulation box containing poly(4-hydroxystyrene) (PHS) base polymers and triphenylsulfonium based PAGs. Our calculations reveal that ion-pair interactions govern the microscopic distributions of the polymer base and PAG molecules, resulting in a highly inhomogeneous system with nonuniform nanoscale chemical domains. Furthermore, the theoretical structures were used in combination of quantum chemical calculations and the Marcus theory to evaluate electron transfer rates between molecular sites, and then kinetic Monte Carlo simulations were carried out to model electron transfer dynamics with molecular structure details taken into consideration. As a result, the portion of thermalized electrons that are absorbed by the PAGs and the nanoscale spatial distribution of generated acids can be estimated. Our data reveal that the nanoscale inhomogeneous distributions of base polymers and PAGs strongly affect the electron transfer and the performance of the resist system. The implications to the performances of EUV resists and key engineering requirements for improved resist systems will also be discussed in this work. Our results shed light on the fundamental structure dependence of photoacid generation and the control of the nanoscale structures as well as base polymer-PAG interactions in EVU resist systems, and we expect these knowledge will be useful for the future development of improved EUV resist systems.

Immediate effects of different types of stretching exercises on badminton jump smash.

PubMed

Jang, Hwi S; Kim, Daeho; Park, Jihong

2018-01-01

Since different types of stretching exercises may alter athletic performance, we compared the effects of three types of stretching exercises on badminton jump smash. Sixteen male collegiate badminton players performed one of three different stretching exercises in a counterbalanced order on different days. Static stretching had seven typical stretches, while dynamic stretching involved nine dynamic movements, and resistance dynamic stretching was performed with weighted vests and dumbbells. Before and after each stretching exercise, subjects performed 20 trials of jump smashes. Dependent measurements were the jump heights during jump smashes, velocities of jump-smashed shuttlecocks, and drop point of jump-smashed shuttlecocks. To test the effects of each stretching exercise, we performed mixed model ANOVAs and calculated between-time effect sizes (ES). Each stretching exercise improved the jump heights during jump smashes (type main effect: F(2,75)=1.19, P=0.31; static stretching: 22.1%, P<0.01, ES=0.98; dynamic stretching: 30.1%, P<0.01, ES=1.49; resistance dynamic stretching: 17.7%, P=0.03, ES=0.98) and velocities of jump-smashed shuttlecocks (type main effect: F(2,75)=2.18, P=0.12; static stretching: 5.7%, P=0.61, ES=0.39; dynamic stretching: 3.4%, P=0.94, ES=0.28; resistance dynamic stretching: 6%, P=0.50, ES=0.66). However, there were no differences among the stretching exercises for any measurement. The drop point of jump-smashed shuttlecocks did not change (interaction: F(2,75)=0.88, P=0.42). All stretching exercises improved badminton jump smash performance, but we could not determine the best protocol. Since badminton requires high-speed movement and explosive force, we suggest performing dynamic stretching or resistance dynamic stretching.

Pyramiding different aphid-resistance genes in elite soybean germplasm to combat dynamic aphid populations

USDA-ARS?s Scientific Manuscript database

The soybean aphid, an invasive species, has posed a significant threat to soybean production in North America since 2001. Use of resistant cultivars is an effective tactic to protect soybean yield. However, the variability and dynamics of aphid populations could limit the effectiveness of host-resis...

Programmers manual for static and dynamic reusable surface insulation stresses (resist)

NASA Technical Reports Server (NTRS)

Ogilvie, P. L.; Levy, A.; Austin, F.; Ojalvo, I. U.

1974-01-01

Programming information for the RESIST program for the dynamic and thermal stress analysis of the space shuttle surface insulation is presented. The overall flow chart of the program, overlay chart, data set allocation, and subprogram calling sequence are given along with a brief description of the individual subprograms and typical subprogram output.

Effects of a resistance training program on balance and fatigue perception in patients with Parkinson's disease: A randomized controlled trial.

PubMed

Ortiz-Rubio, Araceli; Cabrera-Martos, Irene; Torres-Sánchez, Irene; Casilda-López, Jesús; López-López, Laura; Valenza, Marie Carmen

2017-11-22

Fatigue and balance impairment leads to a loss of independence and are important to adequately manage. The objective of this study was to examine the effects of a resistance training program on dynamic balance and fatigue in patients with Parkinson's disease (PD). Randomized controlled trial. Forty-six patients with PD were randomly allocated to an intervention group receiving a 8-week resistance training program focused on lower limbs or to a control group. Balance was assessed using the Mini-BESTest and fatigue was assessed by the Piper Fatigue Scale. Patients in the intervention group improved significantly (p<0.05) on dynamic balance (reactive postural control and total values) and perceived fatigue. An 8-week resistance training program was found to be effective at improving dynamic balance and fatigue in patients with PD. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

PubMed

Wu, Benjamin M; Sabarinath, Sreedharan N; Rand, Kenneth; Johnson, Judith; Derendorf, Hartmut

2011-06-01

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose. A second dose of 200mg or 600 mg CIP, or ceftriaxone (CFX) or gentamicin (GEN) was administered at 12h. Dynamics of the minimum inhibitory concentration (MIC) were assessed using Etest strips before and throughout the CIP treatment period. In addition, the microbroth dilution method was used to evaluate drug susceptibility across a wide range of antibiotics using samples from before and after CIP exposure. A significant loss of CIP effects was observed at the second dose. Cross-resistance to many antibiotics (cefoxitin, cefuroxime, cefotetan, ampicillin and ertapenem) was observed. GEN, but not CFX or high-dose CIP, was sufficient to suppress the developed resistant subpopulation following the initial CIP exposure. The CIP MIC increased substantially from 0.13 μg/mL pre dose to 4 μg/mL at 12h after a CIP dose. In addition, aztreonam induced a similar resistance pattern as CIP, indicating that induction of resistance was not limited to fluoroquinolones. In conclusion, the in vitro dynamic kill curve system revealed that aminoglycosides, more than other classes of antibiotics, were effective against the CIP-induced resistant subpopulations. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

A comparison of two reciprocating instruments using bending stress and cyclic fatigue tests.

PubMed

Scelza, Pantaleo; Harry, Davidowicz; Silva, Licinio Esmeraldo da; Barbosa, Igor Bastos; Scelza, Miriam Zaccaro

2015-01-01

The aim of this study was to comparatively evaluate the bending resistance at 45º, the static and dynamic cyclic fatigue life, and the fracture type of the WaveOne (Dentsply Maillefer, Ballaigues, Switzerland) 25-08 and Reciproc (VDW, Munich, Germany) 25-08 instruments. A total of 60 nickel-titanium (NiTi) instruments (30 Reciproc and 30 WaveOne) from three different lots, each of which was 25 mm in length, were tested. The bending resistance was evaluated through the results of a cantilever-bending test conducted using a universal testing machine. Static and dynamic cyclic fatigue testing was conducted using a custom-made device. For the static and dynamic tests, a cast Ni-Cr-Mo-Ti alloy metal block with an artificial canal measuring 1.77 mm in diameter and 20.00 mm in total length was used. A scanning electron microscope was used to determine the type of fracture. Statistical analyses were performed on the results. The WaveOne instrument was less flexible than the Reciproc (p < 0.05). The Reciproc instrument showed better resistance in the static and dynamic cyclic fatigue tests (p < 0.05). The transverse cross-section and geometry of the instruments were important factors in their resistance to bending and cyclic fracture. Both of the instruments showed ductile-type fracture characteristics. It can be concluded that the Reciproc 25-08 instrument was more resistant to static and dynamic cyclic fatigue than the WaveOne 25-08 instrument, while the WaveOne 25-08 instrument was less flexible. Bending and resistance to cyclic fracture were influenced by the instruments' geometries and transverse cross-sections. Both of the instruments showed ductile-type fracture characteristics.

Inhomogeneity of PAGs in resist film studied by molecular-dynamics simulations for EUV lithography

NASA Astrophysics Data System (ADS)

Toriumi, Minoru; Itani, Toshiro

2014-03-01

EUV resist materials are requested simultaneously to improve the resolution, line-edge roughness (LER), and sensitivity (RLS). In a resist film inhomogeneous structures in nanometer region may have large effects on directly the resolution and LER and indirectly on sensitivity. Inhomogeneity of PAGs in a hybrid resist for EUV lithography was investigated using molecular dynamics simulations. The hybrid resist film showed the inhomogeneous positions and motions of PAG cations and anions. Free volumes in resist matrix influence the motions of PAGs. Molecular structure such as bulky phenyl groups of a PAG cation localize the positions and reduce the motion of a cation. Chemical properties such as ionic interactions and lone-pair interaction also play an important role to determine the inhomogeneity of PAGs. Fluorine interaction enables active motions of PAG anions.

Mathematical modelling of vector-borne diseases and insecticide resistance evolution.

PubMed

Gabriel Kuniyoshi, Maria Laura; Pio Dos Santos, Fernando Luiz

2017-01-01

Vector-borne diseases are important public health issues and, consequently, in silico models that simulate them can be useful. The susceptible-infected-recovered (SIR) model simulates the population dynamics of an epidemic and can be easily adapted to vector-borne diseases, whereas the Hardy-Weinberg model simulates allele frequencies and can be used to study insecticide resistance evolution. The aim of the present study is to develop a coupled system that unifies both models, therefore enabling the analysis of the effects of vector population genetics on the population dynamics of an epidemic. Our model consists of an ordinary differential equation system. We considered the populations of susceptible, infected and recovered humans, as well as susceptible and infected vectors. Concerning these vectors, we considered a pair of alleles, with complete dominance interaction that determined the rate of mortality induced by insecticides. Thus, we were able to separate the vectors according to the genotype. We performed three numerical simulations of the model. In simulation one, both alleles conferred the same mortality rate values, therefore there was no resistant strain. In simulations two and three, the recessive and dominant alleles, respectively, conferred a lower mortality. Our numerical results show that the genetic composition of the vector population affects the dynamics of human diseases. We found that the absolute number of vectors and the proportion of infected vectors are smaller when there is no resistant strain, whilst the ratio of infected people is larger in the presence of insecticide-resistant vectors. The dynamics observed for infected humans in all simulations has a very similar shape to real epidemiological data. The population genetics of vectors can affect epidemiological dynamics, and the presence of insecticide-resistant strains can increase the number of infected people. Based on the present results, the model is a basis for development of other models and for investigating population dynamics.

The dynamic resistance of YBCO coated conductor wire: effect of DC current magnitude and applied field orientation

NASA Astrophysics Data System (ADS)

Jiang, Zhenan; Zhou, Wei; Li, Quan; Yao, Min; Fang, Jin; Amemiya, Naoyuki; Bumby, Chris W.

2018-07-01

Dynamic resistance, which occurs when a HTS coated conductor carries a DC current under an AC magnetic field, can have critical implications for the design of HTS machines. Here, we report measurements of dynamic resistance in a commercially available SuperPower 4 mm-wide YBCO coated conductor, carrying a DC current under an applied AC magnetic field of arbitrary orientation. The reduced DC current, I t/I c0, ranged from 0.01 to 0.9, where I t is the DC current level and I c0 is the self-field critical current of the conductor. The field angle (the angle between the magnetic field and the normal vector of the conductor wide-face) was varied between 0° and 90° at intervals of 10°. We show that the effective width of the conductor under study is ˜12% less than the physical wire width, and we attribute this difference to edge damage of the wire during or after manufacture. We then examine the measured dynamic resistance of this wire under perpendicular applied fields at very low DC current levels. In this regime we find that the threshold field, B th, of the conductor is well described by the nonlinear equation of Mikitik and Brandt. However, this model consistently underestimates the threshold field at higher current levels. As such, the dynamic resistance in a coated conductor under perpendicular magnetic fields is best described using two different equations for each of the low and high DC current regimes, respectively. At low DC currents where I t/I c0 ≤ 0.1, the nonlinear relationship of Mikitik and Brandt provides the closest agreement with experimental data. However, in the higher current regime where I t/I c0 ≥ 0.2, closer agreement is obtained using a simple linear expression which assumes a current-independent penetration field. We further show that for the conductor studied here, the measured dynamic resistance at different field angles is dominated by the perpendicular magnetic field component, with negligible contribution from the parallel component. Our findings now enable the dynamic resistance of a single conductor to be analytically determined for a very wide range of DC currents and at all applied field angles.

Microbial phylogeny determines transcriptional response of resistome to dynamic composting processes.

PubMed

Wang, Cheng; Dong, Da; Strong, P J; Zhu, Weijing; Ma, Zhuang; Qin, Yong; Wu, Weixiang

2017-08-16

Animal manure is a reservoir of antibiotic resistance genes (ARGs) that pose a potential health risk globally, especially for resistance to the antibiotics commonly used in livestock production (such as tetracycline, sulfonamide, and fluoroquinolone). Currently, the effects of biological treatment (composting) on the transcriptional response of manure ARGs and their microbial hosts are not well characterized. Composting is a dynamic process that consists of four distinct phases that are distinguished by the temperature resulting from microbial activity, namely the mesophilic, thermophilic, cooling, and maturing phases. In this study, changes of resistome expression were determined and related to active microbiome profiles during the dynamic composting process. This was achieved by integrating metagenomic and time series metatranscriptomic data for the evolving microbial community during composting. Composting noticeably reduced the aggregated expression level of the manure resistome, which primarily consisted of genes encoding for tetracycline, vancomycin, fluoroquinolone, beta-lactam, and aminoglycoside resistance, as well as efflux pumps. Furthermore, a varied transcriptional response of resistome to composting at the ARG levels was highlighted. The expression of tetracycline resistance genes (tetM-tetW-tetO-tetS) decreased during composting, where distinctive shifts in the four phases of composting were related to variations in antibiotic concentration. Composting had no effect on the expression of sulfonamide and fluoroquinolone resistance genes, which increased slightly during the thermophilic phase and then decreased to initial levels. As indigenous populations switched greatly throughout the dynamic composting, the core resistome persisted and their reservoir hosts' composition was significantly correlated with dynamic active microbial phylogenetic structure. Hosts for sulfonamide and fuoroquinolone resistance genes changed notably in phylognetic structure and underwent an initial increase and then a decrease in abundance. By contrast, hosts for tetracycline resistance genes (tetM-tetW-tetO-tetS) exhibited a constant decline through time. The transcriptional patterns of a core resistome over the course of composting were identified, and microbial phylogeny was the key determinant in defining the varied transcriptional response of resistome to this dynamic biological process. This research demonstrated the benefits of composting for manure treatment. It reduced the risk of emerging environmental contaminants such as tetracyclines, tetracycline resistance genes, and clinically relevant pathogens carrying ARGs, as well as RNA viruses and bacteriophages.

Transmission intensity and drug resistance in malaria population dynamics: implications for climate change.

PubMed

Artzy-Randrup, Yael; Alonso, David; Pascual, Mercedes

2010-10-26

Although the spread of drug resistance and the influence of climate change on malaria are most often considered separately, these factors have the potential to interact through altered levels of transmission intensity. The influence of transmission intensity on the evolution of drug resistance has been addressed in theoretical studies from a population genetics' perspective; less is known however on how epidemiological dynamics at the population level modulates this influence. We ask from a theoretical perspective, whether population dynamics can explain non-trivial, non-monotonic, patterns of treatment failure with transmission intensity, and, if so, under what conditions. We then address the implications of warmer temperatures in an East African highland, where, as in other similar regions at the altitudinal edge of malaria's distribution, there has been a pronounced increase of cases from the 1970s to the 1990s. Our theoretical analyses, with a transmission model that includes different levels of immunity, demonstrate that an increase in transmission beyond a threshold can lead to a decrease in drug resistance, as previously shown, but that a second threshold may occur and lead to the re-establishment of drug resistance. Estimates of the increase in transmission intensity from the 1970s to the 1990s for the Kenyan time series, obtained by fitting the two-stage version of the model with an explicit representation of vector dynamics, suggest that warmer temperatures are likely to have moved the system towards the first threshold, and in so doing, to have promoted the faster spread of drug resistance. Climate change and drug resistance can interact and need not be considered as alternative explanations for trends in disease incidence in this region. Non-monotonic patterns of treatment failure with transmission intensity similar to those described as the 'valley phenomenon' for Uganda can result from epidemiological dynamics but under poorly understood assumptions.

Dynamic response of gold nanoparticle chemiresistors to organic analytes in aqueous solution.

PubMed

Müller, Karl-Heinz; Chow, Edith; Wieczorek, Lech; Raguse, Burkhard; Cooper, James S; Hubble, Lee J

2011-10-28

We investigate the response dynamics of 1-hexanethiol-functionalized gold nanoparticle chemiresistors exposed to the analyte octane in aqueous solution. The dynamic response is studied as a function of the analyte-water flow velocity, the thickness of the gold nanoparticle film and the analyte concentration. A theoretical model for analyte limited mass-transport is used to model the analyte diffusion into the film, the partitioning of the analyte into the 1-hexanethiol capping layers and the subsequent swelling of the film. The degree of swelling is then used to calculate the increase of the electron tunnel resistance between adjacent nanoparticles which determines the resistance change of the film. In particular, the effect of the nonlinear relationship between resistance and swelling on the dynamic response is investigated at high analyte concentration. Good agreement between experiment and the theoretical model is achieved. This journal is © the Owner Societies 2011

Functioning efficiency of intermediate coolers of multistage steam-jet ejectors of steam turbines

NASA Astrophysics Data System (ADS)

Aronson, K. E.; Ryabchikov, A. Yu.; Brodov, Yu. M.; Zhelonkin, N. V.; Murmanskii, I. B.

2017-03-01

Designs of various types of intermediate coolers of multistage ejectors are analyzed and thermal effectiveness and gas-dynamic resistance of coolers are estimated. Data on quantity of steam condensed from steam-air mixture in stage I of an ejector cooler was obtained on the basis of experimental results. It is established that the amount of steam condensed in the cooler constitutes 0.6-0.7 and is almost independent of operating steam pressure (and, consequently, of steam flow) and air amount in steam-air mixture. It is suggested to estimate the amount of condensed steam in a cooler of stage I based on comparison of computed and experimental characteristics of stage II. Computation taking this hypothesis for main types of mass produced multistage ejectors into account shows that 0.60-0.85 of steam amount should be condensed in stage I of the cooler. For ejectors with "pipe-in-pipe" type coolers (EPO-3-200) and helical coolers (EO-30), amount of condensed steam may reach 0.93-0.98. Estimation of gas-dynamic resistance of coolers shows that resistance from steam side in coolers with built-in and remote pipe bundle constitutes 100-300 Pa. Gas-dynamic resistance of "pipein- pipe" and helical type coolers is significantly higher (3-6 times) compared with pipe bundle. However, performance by "dry" (atmospheric) air is higher for ejectors with relatively high gas-dynamic resistance of coolers than those with low resistance at approximately equal operating flow values of ejectors.

Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling

PubMed Central

Jacobs, Matthieu; Grégoire, Nicolas; Couet, William; Bulitta, Jurgen B.

2016-01-01

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 ultimately patients. PMID:26967893

Rapport-Building with Resistant Children: Re-Conceptualizing Relational Dynamics

ERIC Educational Resources Information Center

Gold, Joshua M.

2006-01-01

This paper briefly reviews existing conceptualizations of resistance in counseling children. The author posits that resistance is an "expected" aspect of all counseling and offers an alternative orientation toward client resistance based on exploring the child's "helping narratives." Two case studies illustrate the implementation of this…

Do differences in inducible resistance explain the population dynamics of birch and pine defoliators?

Treesearch

Seppo Neuvonen; Pekka Niemela

1991-01-01

Damage inflicted by insects may trigger responses in their host plants resulting either in immediate effects on herbivores either rapidly or in effects upon subsequent herbivore generations. Differentiation between rapid and delayed inducible resistance is essential since the two responses affect the population dynamics of herbivores in fundamentally different ways (...

The experimental evolution of herbicide resistance in Chlamydomonas reinhardtii results in a positive correlation between fitness in the presence and absence of herbicides.

PubMed

Vogwill, T; Lagator, M; Colegrave, N; Neve, P

2012-10-01

Pleiotropic fitness trade-offs will be key determinants of the evolutionary dynamics of selection for pesticide resistance. However, for herbicide resistance, empirical support for a fitness cost of resistance is mixed, and it is therefore also questionable what further ecological trade-offs can be assumed to apply to herbicide resistance. Here, we test the existence of trade-offs by experimentally evolving herbicide resistance in Chlamydomonas reinhardtii. Although fitness costs are detected for all herbicides, we find that, counterintuitively, the most resistant populations also have the lowest fitness costs as measured by growth rate in the ancestral environment. Furthermore, after controlling for differences in the evolutionary dynamics of resistance to different herbicides, we also detect significant positive correlations between resistance, fitness in the ancestral environment and cross-resistance to other herbicides. We attribute this to the highest levels of nontarget-site resistance being achieved by fixing mutations that more broadly affect cellular physiology, which results in both more cross-resistance and less overall antagonistic pleiotropy on maximum growth rate. Consequently, the lack of classical ecological trade-offs could present a major challenge for herbicide resistance management. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Resistance factors for 100% dynamic testing, with and without static load tests.

DOT National Transportation Integrated Search

2011-05-01

Current department of transportation (DOT) and Federal Highway Administration (FHWA) practice has highly : variable load and resistance factor design (LRFD) resistance factors, , for driven piles from design (e.g., Standard : Penetration Tests (SPT...

Antibiotic resistance in the wild: an eco-evolutionary perspective.

PubMed

Hiltunen, Teppo; Virta, Marko; Laine, Anna-Liisa

2017-01-19

The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Authors.

Antibiotic resistance in the wild: an eco-evolutionary perspective

PubMed Central

Virta, Marko

2017-01-01

The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences'. PMID:27920384

The effect of resistance level and stability demands on recruitment patterns and internal loading of spine in dynamic flexion and extension using a simple trunk model.

PubMed

Zeinali-Davarani, Shahrokh; Shirazi-Adl, Aboulfazl; Dariush, Behzad; Hemami, Hooshang; Parnianpour, Mohamad

2011-07-01

The effects of external resistance on the recruitment of trunk muscles in sagittal movements and the coactivation mechanism to maintain spinal stability were investigated using a simple computational model of iso-resistive spine sagittal movements. Neural excitation of muscles was attained based on inverse dynamics approach along with a stability-based optimisation. The trunk flexion and extension movements between 60° flexion and the upright posture against various resistance levels were simulated. Incorporation of the stability constraint in the optimisation algorithm required higher antagonistic activities for all resistance levels mostly close to the upright position. Extension movements showed higher coactivation with higher resistance, whereas flexion movements demonstrated lower coactivation indicating a greater stability demand in backward extension movements against higher resistance at the neighbourhood of the upright posture. Optimal extension profiles based on minimum jerk, work and power had distinct kinematics profiles which led to recruitment patterns with different timing and amplitude of activation.

Direct observation of oxygen vacancy-driven structural and resistive phase transitions in La2/3Sr1/3MnO3

NASA Astrophysics Data System (ADS)

Yao, Lide; Inkinen, Sampo; van Dijken, Sebastiaan

2017-02-01

Resistive switching in transition metal oxides involves intricate physical and chemical behaviours with potential for non-volatile memory and memristive devices. Although oxygen vacancy migration is known to play a crucial role in resistive switching of oxides, an in-depth understanding of oxygen vacancy-driven effects requires direct imaging of atomic-scale dynamic processes and their real-time impact on resistance changes. Here we use in situ transmission electron microscopy to demonstrate reversible switching between three resistance states in epitaxial La2/3Sr1/3MnO3 films. Simultaneous high-resolution imaging and resistance probing indicate that the switching events are caused by the formation of uniform structural phases. Reversible horizontal migration of oxygen vacancies within the manganite film, driven by combined effects of Joule heating and bias voltage, predominantly triggers the structural and resistive transitions. Our findings open prospects for ionotronic devices based on dynamic control of physical properties in complex oxide nanostructures.

Dissimilar Fitness Associated with Resistance to Fluoroquinolones Influences Clonal Dynamics of Various Multiresistant Bacteria.

PubMed

Fuzi, Miklos

2016-01-01

Fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae. The resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. Moreover, a similar mechanism was recently proposed for the emergence of the H30 and H30R lineages of ESBL-producing E. coli and the major international clone (ribotype 027) of Clostridium difficile. Furthermore, several additional international clones of various multiresistant bacteria are suspect to have been selected by an analogous process. An ability to develop favorable mutations in the gyrase and topoisomerase IV genes seems to be a prerequisite for pathogens to retain fitness while showing high-level resistance to fluoroquinolones. Since, the consumption of other "non-fluoroquinolone" groups of antibiotics have also contributed to the rise in resistance rates a more judicious use of antibiotics in general and of fluoroquinolones in particular could ameliorate the international resistance situation.

ARC-1995-95-HC-379

NASA Image and Video Library

1995-01-01

'Fluid Dynamics,' mixed media by Tina York depicts fluid dynamics studies at the Ames Research Center. The purpose of such studies is to learn more about what happens to an object when it encounters the friction of atmospheric resistence (such as a plane encountering resistance as it speeds through the air). used in Ames 60 year history by Glenn Bugos NASA SP-4314

Bifurcation analysis and global dynamics of a mathematical model of antibiotic resistance in hospitals.

PubMed

Cen, Xiuli; Feng, Zhilan; Zheng, Yiqiang; Zhao, Yulin

2017-12-01

Antibiotic-resistant bacteria have posed a grave threat to public health by causing a number of nosocomial infections in hospitals. Mathematical models have been used to study transmission dynamics of antibiotic-resistant bacteria within a hospital and the measures to control antibiotic resistance in nosocomial pathogens. Studies presented in Lipstich et al. (Proc Natl Acad Sci 97(4):1938-1943, 2000) and Lipstich and Bergstrom (Infection control in the ICU environment. Kluwer, Boston, 2002) have provided valuable insights in understanding the transmission of antibiotic-resistant bacteria in a hospital. However, their results are limited to numerical simulations of a few different scenarios without analytical analyses of the models in broader parameter regions that are biologically feasible. Bifurcation analysis and identification of the global stability conditions can be very helpful for assessing interventions that are aimed at limiting nosocomial infections and stemming the spread of antibiotic-resistant bacteria. In this paper we study the global dynamics of the mathematical model of antibiotic resistance in hospitals considered in Lipstich et al. (2000) and Lipstich and Bergstrom (2002). The invasion reproduction number [Formula: see text] of antibiotic-resistant bacteria is derived, and the relationship between [Formula: see text] and two control reproduction numbers of sensitive bacteria and resistant bacteria ([Formula: see text] and [Formula: see text]) is established. More importantly, we prove that a backward bifurcation may occur at [Formula: see text] when the model includes superinfection, which is not mentioned in Lipstich and Bergstrom (2002). More specifically, there exists a new threshold [Formula: see text], such that if [Formula: see text], then the system can have two positive interior equilibria, which leads to an interesting bistable phenomenon. This may have critical implications for controlling the antibiotic-resistance in a hospital.

[Dynamics of drug resistance in Proteus mirabilis cultures 1970-1985].

PubMed

Shvidenko, I G

1988-04-01

Resistance of 669 clinical strains of Proteus mirabilis to 18 chemotherapeutic drugs was studied in dynamics within 1970-1985. An increase in the number of cultures resistant to ampicillin and carbenicillin was noted while the number of cultures resistant to cephalosporines did not change. Within the period from 1970 to 1975 there was observed a marked increase in the number of Proteus strains resistant to aminoglycoside antibiotics. After that period their number gradually lowered and in 1985 reached the level of 1970. Beginning from 1973 there were observed a decrease in the number of Proteus chloramphenicol resistant strains and simultaneous occurrence of cultures sensitive to this antibiotic. The predominating number of the tested strains preserved during the whole observation period their resistance to tetracycline, doxycycline, rifampicin, novobiocin, furazolidone and furagin. No increase in the number of Proteus strains with multiple drug resistance including those resistant to 5-7 drugs was noted in the observation periods of 1970-1975, 1980 and 1985. The most frequent were Proteus strains resistant to 2-4 drugs. Among them cultures resistant to chloramphenicol and aminoglycoside antibiotics of the first generation predominated. Grouping of the strains by the same resistance spectra provided dividing the rested cultures of Proteus mirabilis into 69 variants.

Enhanced oxidation resistance of active nanostructures via dynamic size effect

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

Liu, Yun; Yang, Fan; Zhang, Yi

A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O 2 and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeOmore » NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O 2. We find this dynamic size effect to govern the chemical properties of active NSs.« less

Enhanced oxidation resistance of active nanostructures via dynamic size effect

DOE PAGES

Liu, Yun; Yang, Fan; Zhang, Yi; ...

2017-02-22

A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O 2 and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeOmore » NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O 2. We find this dynamic size effect to govern the chemical properties of active NSs.« less

Density-dependent resistance of the gypsy moth, Lymantria dispar, to its nucleopolyhedrovirus

Treesearch

James R. Reilly; Ann E. Hajek

2007-01-01

The processes controlling disease resistance can strongly influence the population dynamics of insect outbreaks. Evidence that disease resistance is density-dependent is accumulating, but the exact form of this relationship is highly variable from species to species.

Clonal Expansion during Staphylococcus aureus Infection Dynamics Reveals the Effect of Antibiotic Intervention

PubMed Central

McVicker, Gareth; Prajsnar, Tomasz K.; Williams, Alexander; Wagner, Nelly L.; Boots, Michael; Renshaw, Stephen A.; Foster, Simon J.

2014-01-01

To slow the inexorable rise of antibiotic resistance we must understand how drugs impact on pathogenesis and influence the selection of resistant clones. Staphylococcus aureus is an important human pathogen with populations of antibiotic-resistant bacteria in hospitals and the community. Host phagocytes play a crucial role in controlling S. aureus infection, which can lead to a population “bottleneck” whereby clonal expansion of a small fraction of the initial inoculum founds a systemic infection. Such population dynamics may have important consequences on the effect of antibiotic intervention. Low doses of antibiotics have been shown to affect in vitro growth and the generation of resistant mutants over the long term, however whether this has any in vivo relevance is unknown. In this work, the population dynamics of S. aureus pathogenesis were studied in vivo using antibiotic-resistant strains constructed in an isogenic background, coupled with systemic models of infection in both the mouse and zebrafish embryo. Murine experiments revealed unexpected and complex bacterial population kinetics arising from clonal expansion during infection in particular organs. We subsequently elucidated the effect of antibiotic intervention within the host using mixed inocula of resistant and sensitive bacteria. Sub-curative tetracycline doses support the preferential expansion of resistant microorganisms, importantly unrelated to effects on growth rate or de novo resistance acquisition. This novel phenomenon is generic, occurring with methicillin-resistant S. aureus (MRSA) in the presence of β-lactams and with the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant clones at low antibiotic levels can result in a rapid increase in their prevalence under conditions that would previously not be thought to favor them. Our results have key implications for the design of effective treatment regimes to limit the spread of antimicrobial resistance, where inappropriate usage leading to resistance may reduce the efficacy of life-saving drugs. PMID:24586163

Kernel Density Estimation as a Measure of Environmental Exposure Related to Insulin Resistance in Breast Cancer Survivors.

PubMed

Jankowska, Marta M; Natarajan, Loki; Godbole, Suneeta; Meseck, Kristin; Sears, Dorothy D; Patterson, Ruth E; Kerr, Jacqueline

2017-07-01

Background: Environmental factors may influence breast cancer; however, most studies have measured environmental exposure in neighborhoods around home residences (static exposure). We hypothesize that tracking environmental exposures over time and space (dynamic exposure) is key to assessing total exposure. This study compares breast cancer survivors' exposure to walkable and recreation-promoting environments using dynamic Global Positioning System (GPS) and static home-based measures of exposure in relation to insulin resistance. Methods: GPS data from 249 breast cancer survivors living in San Diego County were collected for one week along with fasting blood draw. Exposure to recreation spaces and walkability was measured for each woman's home address within an 800 m buffer (static), and using a kernel density weight of GPS tracks (dynamic). Participants' exposure estimates were related to insulin resistance (using the homeostatic model assessment of insulin resistance, HOMA-IR) controlled by age and body mass index (BMI) in linear regression models. Results: The dynamic measurement method resulted in greater variability in built environment exposure values than did the static method. Regression results showed no association between HOMA-IR and home-based, static measures of walkability and recreation area exposure. GPS-based dynamic measures of both walkability and recreation area were significantly associated with lower HOMA-IR ( P < 0.05). Conclusions: Dynamic exposure measurements may provide important evidence for community- and individual-level interventions that can address cancer risk inequities arising from environments wherein breast cancer survivors live and engage. Impact: This is the first study to compare associations of dynamic versus static built environment exposure measures with insulin outcomes in breast cancer survivors. Cancer Epidemiol Biomarkers Prev; 26(7); 1078-84. ©2017 AACR . ©2017 American Association for Cancer Research.

The Effects of Multiple-Joint Isokinetic Resistance Training on Maximal Isokinetic and Dynamic Muscle Strength and Local Muscular Endurance.

PubMed

Ratamess, Nicholas A; Beller, Noah A; Gonzalez, Adam M; Spatz, Gregory E; Hoffman, Jay R; Ross, Ryan E; Faigenbaum, Avery D; Kang, Jie

2016-03-01

The transfer of training effects of multiple-joint isokinetic resistance training to dynamic exercise performance remain poorly understood. Thus, the purpose of the present study was to investigate the magnitude of isokinetic and dynamic one repetition-maximum (1RM) strength and local muscular endurance increases after 6 weeks of multiple-joint isokinetic resistance training. Seventeen women were randomly assigned to either an isokinetic resistance training group (IRT) or a non-exercising control group (CTL). The IRT group underwent 6 weeks of training (2 days per week) consisting of 5 sets of 6-10 repetitions at 75-85% of subjects' peak strength for the isokinetic chest press and seated row exercises at an average linear velocity of 0.15 m s(-1) [3-sec concentric (CON) and 3-sec eccentric (ECC) phases]. Peak CON and ECC force during the chest press and row, 1RM bench press and bent-over row, and maximum number of modified push-ups were assessed pre and post training. A 2 x 2 analysis of variance with repeated measures and Tukey's post hoc tests were used for data analysis. The results showed that 1RM bench press (from 38.6 ± 6.7 to 43.0 ± 5.9 kg), 1RM bent-over row (from 40.4 ± 7.7 to 45.5 ± 7.5 kg), and the maximal number of modified push-ups (from 39.5 ± 13.6 to 55.3 ± 13.1 repetitions) increased significantly only in the IRT group. Peak isokinetic CON and ECC force in the chest press and row significantly increased in the IRT group. No differences were shown in the CTL group for any measure. These data indicate 6 weeks of multiple-joint isokinetic resistance training increases dynamic muscle strength and local muscular endurance performance in addition to specific isokinetic strength gains in women. Key pointsMultiple-joint isokinetic resistance training increases dynamic maximal muscular strength, local muscular endurance, and maximal isokinetic strength in women.Multiple-joint isokinetic resistance training increased 1RM strength in the bench press (by 10.2%), bent-over barbell row (by 11.2%), and maximal modified push-up performance (by 28.6%) indicating a carryover of training effects to dynamic exercise performance.The carryover effects may be attractive to strength training and conditioning professionals seeking to include alternative modalities such as multiple-joint isokinetic dynamometers to resistance training programs.

The Effects of Multiple-Joint Isokinetic Resistance Training on Maximal Isokinetic and Dynamic Muscle Strength and Local Muscular Endurance

PubMed Central

Ratamess, Nicholas A.; Beller, Noah A.; Gonzalez, Adam M.; Spatz, Gregory E.; Hoffman, Jay R.; Ross, Ryan E.; Faigenbaum, Avery D.; Kang, Jie

2016-01-01

The transfer of training effects of multiple-joint isokinetic resistance training to dynamic exercise performance remain poorly understood. Thus, the purpose of the present study was to investigate the magnitude of isokinetic and dynamic one repetition-maximum (1RM) strength and local muscular endurance increases after 6 weeks of multiple-joint isokinetic resistance training. Seventeen women were randomly assigned to either an isokinetic resistance training group (IRT) or a non-exercising control group (CTL). The IRT group underwent 6 weeks of training (2 days per week) consisting of 5 sets of 6-10 repetitions at 75-85% of subjects’ peak strength for the isokinetic chest press and seated row exercises at an average linear velocity of 0.15 m s-1 [3-sec concentric (CON) and 3-sec eccentric (ECC) phases]. Peak CON and ECC force during the chest press and row, 1RM bench press and bent-over row, and maximum number of modified push-ups were assessed pre and post training. A 2 x 2 analysis of variance with repeated measures and Tukey’s post hoc tests were used for data analysis. The results showed that 1RM bench press (from 38.6 ± 6.7 to 43.0 ± 5.9 kg), 1RM bent-over row (from 40.4 ± 7.7 to 45.5 ± 7.5 kg), and the maximal number of modified push-ups (from 39.5 ± 13.6 to 55.3 ± 13.1 repetitions) increased significantly only in the IRT group. Peak isokinetic CON and ECC force in the chest press and row significantly increased in the IRT group. No differences were shown in the CTL group for any measure. These data indicate 6 weeks of multiple-joint isokinetic resistance training increases dynamic muscle strength and local muscular endurance performance in addition to specific isokinetic strength gains in women. Key points Multiple-joint isokinetic resistance training increases dynamic maximal muscular strength, local muscular endurance, and maximal isokinetic strength in women. Multiple-joint isokinetic resistance training increased 1RM strength in the bench press (by 10.2%), bent-over barbell row (by 11.2%), and maximal modified push-up performance (by 28.6%) indicating a carryover of training effects to dynamic exercise performance. The carryover effects may be attractive to strength training and conditioning professionals seeking to include alternative modalities such as multiple-joint isokinetic dynamometers to resistance training programs. PMID:26957924

Host population structure and treatment frequency maintain balancing selection on drug resistance

PubMed Central

Baskerville, Edward B.; Colijn, Caroline; Hanage, William; Fraser, Christophe; Lipsitch, Marc

2017-01-01

It is a truism that antimicrobial drugs select for resistance, but explaining pathogen- and population-specific variation in patterns of resistance remains an open problem. Like other common commensals, Streptococcus pneumoniae has demonstrated persistent coexistence of drug-sensitive and drug-resistant strains. Theoretically, this outcome is unlikely. We modelled the dynamics of competing strains of S. pneumoniae to investigate the impact of transmission dynamics and treatment-induced selective pressures on the probability of stable coexistence. We find that the outcome of competition is extremely sensitive to structure in the host population, although coexistence can arise from age-assortative transmission models with age-varying rates of antibiotic use. Moreover, we find that the selective pressure from antibiotics arises not so much from the rate of antibiotic use per se but from the frequency of treatment: frequent antibiotic therapy disproportionately impacts the fitness of sensitive strains. This same phenomenon explains why serotypes with longer durations of carriage tend to be more resistant. These dynamics may apply to other potentially pathogenic, microbial commensals and highlight how population structure, which is often omitted from models, can have a large impact. PMID:28835542

Effects of quadriceps strength after static and dynamic whole-body vibration exercise.

PubMed

Bush, Jill A; Blog, Gabriel L; Kang, Jie; Faigenbaum, Avery D; Ratamess, Nicholas A

2015-05-01

Numerous studies have shown performance benefits including whole-body vibration (WBV) as a training modality or an acute exercise protocol when used as a component of the resistance training program. Some studies have indicated that performing dynamic exercises as compared with static position exercises while exposed to WBV might be beneficial; however, evidence is lacking. Thus, the purpose of this study was to determine if an acute bout of dynamic versus static squats performed during WBV results in increase in quadriceps force production by means of dynamic isokinetic knee extension and flexion exercise. Nonresistance-trained healthy young men and women (N = 21) of 18-25 years participated in 4 protocols with 2-week rest in-between. Protocol 1 consisted of 5 sets of 10 dynamic squats without vibration; Protocol 2: 5 sets of 30-second static squats without vibration; Protocol 3: 5 sets of 10 dynamic squats with 30-Hz WBV for a total of 2.5 minutes; and Protocol 4: 5 sets of 30-second static squats with 30-Hz WBV for a total of 2.5 minutes. Prestrength tests (1 set of 4 repetitions at 100° · s(-1) for the knee extension exercise) was performed within 5 minutes of starting each protocol, and poststrength testing was performed within 1 minute of completing each protocol. Strength outcomes were analyzed by repeated measures analysis of variance with a significance level set at p ≤ 0.05. A significant decrease in strength was observed after dynamic and static squats without WBV (p = 0.002); an increase in strength after dynamic squats with WBV (p = 0.003); and a decrease in strength after static squats with WBV (p = 0.003). The inclusion of WBV to dynamic resistance exercise can be an added modality to increase strength. Whole-body vibration can have varied effects in altering muscle strength in untrained individuals according to the type of resistance training performed. As a dynamic squat with WBV seems to immediately potentiate neuromuscular functioning, the combination of dynamic exercises and WBV could be used as a potential warm-up procedure before resistance exercise.

[Change in drug resistance of Staphylococcus aureus].

PubMed

Lin, Yan; Liu, Yan; Luo, Yan-Ping; Liu, Chang-Ting

2013-11-01

To analyze the change in drug resistance of Staphylococcus aureus (SAU) in the PLA general hospital from January 2008 to December 2012, and to provide solid evidence to support the rational use of antibiotics for clinical applications. The SAU strains isolated from clinical samples in the hospital were collected and subjected to the Kirby-Bauer disk diffusion test. The results were assessed based on the 2002 American National Committee for Clinical Laboratory Standards (NCCLS) guidelines. SAU strains were mainly isolated from sputum, urine, blood and wound excreta and distributed in penology, neurology wards, orthopedics and surgery ICU wards. Except for glycopeptide drugs, methicillin-resistant Staphylococcus aureus (MRSA) had a higher drug resistance rate than those of the other drugs and had significantly more resistance than methicillin-sensitive Staphylococcus aureus (MSSA) (P < 0.05). In the dynamic observation of drug resistance, we discovered a gradual increase in drug resistance to fourteen test drugs during the last five years. Drug resistance rate of SAU stayed at a higher level over the last five years; moreover, the detection ratio of MRSA keeps rising year by year. It is crucial for physicians to use antibiotics rationally and monitor the change in drug resistance in a dynamic way.

Characteristics of dynamic magnetic resonance image enhancement in prolactinomas resistant to dopamine agonist therapy.

PubMed

Guo, Qinghua; Erickson, Bradley J; Chang, Alice Y; Erickson, Dana

2015-03-01

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07-3.27; P = 0.02). Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

Magnetotail particle dynamics and transport

NASA Technical Reports Server (NTRS)

Speiser, Theodore W.

1995-01-01

The main thrust of our research is to study the consequences of particle dynamics in the current sheet region of the magnetotail. The importance of understanding particle dynamics, in and near current sheets, cannot be over estimated, especially in light of NASA's recent interest in developing global circulation models to predict space weather. We have embarked on a long-term study to investigate the electrical resistance due to chaotic behavior, compare this resistance to inertial effects, and relate it to that resistance required in MHD modeling for reconnection to proceed. Using a single-particle model and observations, we have also found that a neutral line region can be remotely sensed. We plan to evaluate other cases of satellite observations near times of substorm onset to elucidate the relationship between the temporal development of a near-Earth neutral line and onset.

Dynamic absorption coefficients of chemically amplified resists and nonchemically amplified resists at extreme ultraviolet

NASA Astrophysics Data System (ADS)

Fallica, Roberto; Stowers, Jason K.; Grenville, Andrew; Frommhold, Andreas; Robinson, Alex P. G.; Ekinci, Yasin

2016-07-01

The dynamic absorption coefficients of several chemically amplified resists (CAR) and non-CAR extreme ultraviolet (EUV) photoresists are measured experimentally using a specifically developed setup in transmission mode at the x-ray interference lithography beamline of the Swiss Light Source. The absorption coefficient α and the Dill parameters ABC were measured with unprecedented accuracy. In general, the α of resists match very closely with the theoretical value calculated from elemental densities and absorption coefficients, whereas exceptions are observed. In addition, through the direct measurements of the absorption coefficients and dose-to-clear values, we introduce a new figure of merit called chemical sensitivity to account for all the postabsorption chemical reaction ongoing in the resist, which also predicts a quantitative clearing volume and clearing radius, due to the photon absorption in the resist. These parameters may help provide deeper insight into the underlying mechanisms of the EUV concepts of clearing volume and clearing radius, which are then defined and quantitatively calculated.

Unraveling the effects of amino acid substitutions enhancing lipase resistance to an ionic liquid: a molecular dynamics study.

PubMed

Zhao, Jing; Frauenkron-Machedjou, Victorine Josiane; Fulton, Alexander; Zhu, Leilei; Davari, Mehdi D; Jaeger, Karl-Erich; Schwaneberg, Ulrich; Bocola, Marco

2018-04-04

Understanding of the structural and dynamic properties of enzymes in non-aqueous media (e.g., ionic liquids, ILs) is highly attractive for protein engineers and synthetic biochemists. Despite a growing number of molecular dynamics (MD) simulation studies on the influence of different ILs on wild-type enzymes, the effects of various amino acid substitutions on the stability and activity of enzymes in ILs remain to be unraveled at the molecular level. Herein, we selected fifty previously reported Bacillus subtilis lipase A (BSLA) variants with increased resistance towards an IL (15 vol% 1-butyl-3-methylimidazolium trifluoromethanesulfonate; [Bmim][TfO]), and also ten non-resistant BSLA variants for a MD simulation study to identify the underlying molecular principles. Some important properties differentiating resistant and non-resistant BSLA variants from wild-type were elucidated. Results show that, in 15 vol% [Bmim][TfO] aqueous solution, 40% and 60% of non-resistant variants have lower and equal probabilities to form a catalytically important hydrogen bond between S77 and H156 compared to wild-type, whereas 36% and 56% of resistant variants show increased and equal probabilities, respectively. Introducing positively charged amino acids close to the substrate-binding cleft for instance I12R is beneficial for the BSLA resistance towards 15 vol% [Bmim][TfO], likely due to the reduced probability of [Bmim]+ cations clustering near the cleft. In contrast, substitution with a large hydrophobic residue like I12F can block the cleft through hydrophobic interaction with a neighboring nonpolar loop 134-137 or/and an attractive π-π interaction with [Bmim]+ cations. In addition, the resistant variants having polar substitutions on the surface show higher ability to stabilize the surface water molecule network in comparison to non-resistant variants. This study can guide experimentalists to rationally design promising IL-resistant enzymes, and contribute to a deeper understanding of protein-IL interactions at the molecular level.

Enriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains.

PubMed

Lavania, Mallika; Singh, Itu; Turankar, Ravindra P; Gupta, Anuj Kumar; Ahuja, Madhvi; Pathak, Vinay; Sengupta, Utpal

2018-01-01

Despite more than three decades of multidrug therapy (MDT), leprosy remains a major public health issue in several endemic countries, including India. The emergence of drug resistance in Mycobacterium leprae (M. leprae) is a cause of concern and poses a threat to the leprosy-control program, which might ultimately dampen the achievement of the elimination program of the country. Rifampicin resistance in clinical strains of M. leprae are supposed to arise from harboring bacterial strains with mutations in the 81-bp rifampicin resistance determining region (RRDR) of the rpoB gene. However, complete dynamics of rifampicin resistance are not explained only by this mutation in leprosy strains. To understand the role of other compensatory mutations and transmission dynamics of drug-resistant leprosy, a genome-wide sequencing of 11 M. leprae strains - comprising five rifampicin-resistant strains, five sensitive strains, and one reference strain - was done in this study. We observed the presence of compensatory mutations in two rifampicin-resistant strains in rpoC and mmpL7 genes, along with rpoB , that may additionally be responsible for conferring resistance in those strains. Our findings support the role for compensatory mutation(s) in RNA polymerase gene(s), resulting in rifampicin resistance in relapsed leprosy patients.

Population biological principles of drug-resistance evolution in infectious diseases.

PubMed

zur Wiesch, Pia Abel; Kouyos, Roger; Engelstädter, Jan; Regoes, Roland R; Bonhoeffer, Sebastian

2011-03-01

The emergence of resistant pathogens in response to selection pressure by drugs and their possible disappearance when drug use is discontinued are evolutionary processes common to many pathogens. Population biological models have been used to study the dynamics of resistance in viruses, bacteria, and eukaryotic microparasites both at the level of the individual treated host and of the treated host population. Despite the existence of generic features that underlie such evolutionary dynamics, different conclusions have been reached about the key factors affecting the rate of resistance evolution and how to best use drugs to minimise the risk of generating high levels of resistance. Improved understanding of generic versus specific population biological aspects will help to translate results between different studies, and allow development of a more rational basis for sustainable drug use than exists at present. Copyright © 2011 Elsevier Ltd. All rights reserved.

Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations.

PubMed

Vijayan, R S K; Arnold, Eddy; Das, Kalyan

2014-05-01

HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that is targeted by nucleoside analogs (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). NNRTIs are allosteric inhibitors of RT, and constitute an integral part of several highly active antiretroviral therapy regimens. Under selective pressure, HIV-1 acquires resistance against NNRTIs primarily by selecting mutations around the NNRTI pocket. Complete RT sequencing of clinical isolates revealed that spatially distal mutations arising in connection and the RNase H domain also confer NNRTI resistance and contribute to NRTI resistance. However, the precise structural mechanism by which the connection domain mutations confer NNRTI resistance is poorly understood. We performed 50-ns molecular dynamics (MD) simulations, followed by essential dynamics, free-energy landscape analyses, and network analyses of RT-DNA, RT-DNA-nevirapine (NVP), and N348I/T369I mutant RT-DNA-NVP complexes. MD simulation studies revealed altered global motions and restricted conformational landscape of RT upon NVP binding. Analysis of protein structure network parameters demonstrated a dissortative hub pattern in the RT-DNA complex and an assortative hub pattern in the RT-DNA-NVP complex suggesting enhanced rigidity of RT upon NVP binding. The connection subdomain mutations N348I/T369I did not induce any significant structural change; rather, these mutations modulate the conformational dynamics and alter the long-range allosteric communication network between the connection subdomain and NNRTI pocket. Insights from the present study provide a structural basis for the biochemical and clinical findings on drug resistance caused by the connection and RNase H mutations. Copyright © 2013 Wiley Periodicals, Inc.

Dissimilar Fitness Associated with Resistance to Fluoroquinolones Influences Clonal Dynamics of Various Multiresistant Bacteria

PubMed Central

Fuzi, Miklos

2016-01-01

Fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae. The resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. Moreover, a similar mechanism was recently proposed for the emergence of the H30 and H30R lineages of ESBL-producing E. coli and the major international clone (ribotype 027) of Clostridium difficile. Furthermore, several additional international clones of various multiresistant bacteria are suspect to have been selected by an analogous process. An ability to develop favorable mutations in the gyrase and topoisomerase IV genes seems to be a prerequisite for pathogens to retain fitness while showing high-level resistance to fluoroquinolones. Since, the consumption of other “non-fluoroquinolone” groups of antibiotics have also contributed to the rise in resistance rates a more judicious use of antibiotics in general and of fluoroquinolones in particular could ameliorate the international resistance situation. PMID:27458434

Eco-evolutionary dynamics in a coevolving host-virus system.

PubMed

Frickel, Jens; Sieber, Michael; Becks, Lutz

2016-04-01

Eco-evolutionary dynamics have been shown to be important for understanding population and community stability and their adaptive potential. However, coevolution in the framework of eco-evolutionary theory has not been addressed directly. Combining experiments with an algal host and its viral parasite, and mathematical model analyses we show eco-evolutionary dynamics in antagonistic coevolving populations. The interaction between antagonists initially resulted in arms race dynamics (ARD) with selective sweeps, causing oscillating host-virus population dynamics. However, ARD ended and populations stabilised after the evolution of a general resistant host, whereas a trade-off between host resistance and growth then maintained host diversity over time (trade-off driven dynamics). Most importantly, our study shows that the interaction between ecology and evolution had important consequences for the predictability of the mode and tempo of adaptive change and for the stability and adaptive potential of populations. © 2016 John Wiley & Sons Ltd/CNRS.

Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

ERIC Educational Resources Information Center

Stevenson, Scott W.; Dudley, Gary A.

2001-01-01

Examined whether creatine (CR) monohydrate loading would alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with placebo loading in resistance-trained athletes. Overall, CR loading did not provide an ergogenic benefit for the unilateral dynamic knee extension…

Development of Magnetorheological Resistive Exercise Device for Rowing Machine

PubMed Central

Žiliukas, Pranas

2016-01-01

Training equipment used by professional sportsmen has a great impact on their sport performance. Most universal exercisers may help only to improve the general physical condition due to the specific kinematics and peculiar resistance generated by their loading units. Training of effective techniques and learning of psychomotor skills are possible only when exercisers conform to the movements and resistance typical for particular sports kinematically and dynamically. Methodology of developing a magnetorheological resistive exercise device for generating the desired law of passive resistance force and its application in a lever-type rowing machine are described in the paper. The structural parameters of a controllable hydraulic cylinder type device were found by means of the computational fluid dynamics simulation performed by ANSYS CFX software. Parameters describing the magnetorheological fluid as non-Newtonian were determined by combining numerical and experimental research of the resistance force generated by the original magnetorheological damper. A structural scheme of the device control system was developed and the variation of the strength of magnetic field that affects the magnetorheological fluid circulating in the device was determined, ensuring a variation of the resistance force on the oar handle adequate for the resistance that occurs during a real boat rowing stroke. PMID:27293479

Development of Magnetorheological Resistive Exercise Device for Rowing Machine.

PubMed

Grigas, Vytautas; Šulginas, Anatolijus; Žiliukas, Pranas

2015-01-01

Training equipment used by professional sportsmen has a great impact on their sport performance. Most universal exercisers may help only to improve the general physical condition due to the specific kinematics and peculiar resistance generated by their loading units. Training of effective techniques and learning of psychomotor skills are possible only when exercisers conform to the movements and resistance typical for particular sports kinematically and dynamically. Methodology of developing a magnetorheological resistive exercise device for generating the desired law of passive resistance force and its application in a lever-type rowing machine are described in the paper. The structural parameters of a controllable hydraulic cylinder type device were found by means of the computational fluid dynamics simulation performed by ANSYS CFX software. Parameters describing the magnetorheological fluid as non-Newtonian were determined by combining numerical and experimental research of the resistance force generated by the original magnetorheological damper. A structural scheme of the device control system was developed and the variation of the strength of magnetic field that affects the magnetorheological fluid circulating in the device was determined, ensuring a variation of the resistance force on the oar handle adequate for the resistance that occurs during a real boat rowing stroke.

Collateral Ventilation to Congenital Hyperlucent Lung Lesions Assessed on Xenon-Enhanced Dynamic Dual-Energy CT: an Initial Experience

PubMed Central

Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

2011-01-01

Objective We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Materials and Methods Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Results Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Conclusion Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung. PMID:21228937

Collateral ventilation to congenital hyperlucent lung lesions assessed on xenon-enhanced dynamic dual-energy CT: an initial experience.

PubMed

Goo, Hyun Woo; Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

2011-01-01

We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung.

A new insight into arable weed adaptive evolution: mutations endowing herbicide resistance also affect germination dynamics and seedling emergence.

PubMed

Délye, Christophe; Menchari, Yosra; Michel, Séverine; Cadet, Emilie; Le Corre, Valérie

2013-04-01

Selective pressures exerted by agriculture on populations of arable weeds foster the evolution of adaptive traits. Germination and emergence dynamics and herbicide resistance are key adaptive traits. Herbicide resistance alleles can have pleiotropic effects on a weed's life cycle. This study investigated the pleiotropic effects of three acetyl-coenzyme A carboxylase (ACCase) alleles endowing herbicide resistance on the seed-to-plant part of the life cycle of the grass weed Alopecurus myosuroides. In each of two series of experiments, A. myosuroides populations with homogenized genetic backgrounds and segregating for Leu1781, Asn2041 or Gly2078 ACCase mutations which arose independently were used to compare germination dynamics, survival in the soil and seedling pre-emergence growth among seeds containing wild-type, heterozygous and homozygous mutant ACCase embryos. Asn2041 ACCase caused no significant effects. Gly2078 ACCase major effects were a co-dominant acceleration in seed germination (1·25- and 1·10-fold decrease in the time to reach 50 % germination (T50) for homozygous and heterozygous mutant embryos, respectively). Segregation distortion against homozygous mutant embryos or a co-dominant increase in fatal germination was observed in one series of experiments. Leu1781 ACCase major effects were a co-dominant delay in seed germination (1·41- and 1·22-fold increase in T50 for homozygous and heterozygous mutant embryos, respectively) associated with a substantial co-dominant decrease in fatal germination. Under current agricultural systems, plants carrying Leu1781 or Gly2078 ACCase have a fitness advantage conferred by herbicide resistance that is enhanced or counterbalanced, respectively, by direct pleiotropic effects on the plant phenology. Pleiotropic effects associated with mutations endowing herbicide resistance undoubtedly play a significant role in the evolutionary dynamics of herbicide resistance in weed populations. Mutant ACCase alleles should also prove useful to investigate the role played by seed storage lipids in the control of seed dormancy and germination.

Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Consolino, Lorena; Longo, Dario Livio; Sciortino, Marianna; Dastrù, Walter; Cabodi, Sara; Giovenzana, Giovanni Battista; Aime, Silvio

2017-07-01

Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach. Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K trans ) and vascular volume fraction (v p ). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays. Dynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density (P < 0.0001) and permeability (P = 0.0002) in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K trans and v p , and their related ex vivo values, MVD (r = 0.78 for K trans and r = 0.82 for v p ) and MDD (r = 0.77 for K trans and r = 0.94 for v p ). In addition, higher expression of vascular endothelial growth factor receptors (VEGFR2 and VEFGR3) was seen in GIST430. Dynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.

A novel method to study single-particle dynamics by the resistive pulse technique

NASA Astrophysics Data System (ADS)

Berge, L. I.; Feder, J.; Jøssang, T.

1989-08-01

We have developed a new method, a pressure-reversal technique, which extends the uses of the resistive pulse (Coulter counter) technique to single-particle dynamics. The resistive pulse technique measures the increase in resistance when particles suspended in an electrolyte are transported through a current-carrying aperture. By the new method, the pressure is reversed when a particle exits the pore. A trigger signal, derived from the particle pulses, is used to activate two miniature solenoid valves which serve as pressure switches. In this way, the particle reenters the pore. A single particle flowing back and forth may be studied over a long period of time. The time the particle spends outside the pore between reversals is variable from a few milliseconds to several seconds. We have so far used pore diameters in the range of 3-30 μm. The new technique enables us to study single-particle dissolution and single-particle flow dynamics. The experimental arrangement and the details of the new method are described together with some illustrative measurements.

A thorough investigation of the progressive reset dynamics in HfO{sub 2}-based resistive switching structures

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

Lorenzi, P., E-mail: lorenzi@die.uniroma1.it; Rao, R.; Irrera, F.

2015-09-14

According to previous reports, filamentary electron transport in resistive switching HfO{sub 2}-based metal-insulator-metal structures can be modeled using a diode-like conduction mechanism with a series resistance. Taking the appropriate limits, the model allows simulating the high (HRS) and low (LRS) resistance states of the devices in terms of exponential and linear current-voltage relationships, respectively. In this letter, we show that this simple equivalent circuit approach can be extended to represent the progressive reset transition between the LRS and HRS if a generalized logistic growth model for the pre-exponential diode current factor is considered. In this regard, it is demonstrated heremore » that a Verhulst logistic model does not provide accurate results. The reset dynamics is interpreted as the sequential deactivation of multiple conduction channels spanning the dielectric film. Fitting results for the current-voltage characteristics indicate that the voltage sweep rate only affects the deactivation rate of the filaments without altering the main features of the switching dynamics.« less

Role of muscle mass and mode of contraction in circulatory responses to exercise

NASA Technical Reports Server (NTRS)

Lewis, S. F.; Snell, P. G.; Pettinger, W. A.; Blomqvist, C. G.; Taylor, W. F.; Hamra, M.; Graham, R. M.

1985-01-01

The roles of the mode of contraction (dynamic or static) and active muscle mass in determining the cardiovascular response to exercise has been investigated experimentally in six normal men. Exercise consisted of static handgrip and dynamic handgrip exercise, and static and dynamic knee extension for a period of six minutes. Observed increases in mean arterial pressure after exercise were similar for each mode of contraction, but larger for knee extension than handgrip exercise. Cardiac output increased more for dynamic than for static exercise and for each mode more for knee exercise than for handgrip exercise. Systemic resistance was found to be lower for dynamic than for static exercise, and to decrease from resisting levels by about one third during dynamic knee extension. It is shown that the magnitude of cardiovascular response is related to active muscle mass, but is independent of the contraction mode. Equalization of cardiovascular response was achieved by proportionately larger increases in cardiac output during dynamic exercise. The complete experimental results are given in a table.

Dependence of the residual surface resistance of superconducting radio frequency cavities on the cooling dynamics around T{sub c}

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

Romanenko, A., E-mail: aroman@fnal.gov; Grassellino, A., E-mail: annag@fnal.gov; Melnychuk, O.

We report a strong effect of the cooling dynamics through T{sub c} on the amount of trapped external magnetic flux in superconducting niobium cavities. The effect is similar for fine grain and single crystal niobium and all surface treatments including electropolishing with and without 120 °C baking and nitrogen doping. Direct magnetic field measurements on the cavity walls show that the effect stems from changes in the flux trapping efficiency: slow cooling leads to almost complete flux trapping and higher residual resistance, while fast cooling leads to the much more efficient flux expulsion and lower residual resistance.

Strategies for dynamic soft-landing in capacitive microelectromechanical switches

NASA Astrophysics Data System (ADS)

Jain, Ankit; Nair, Pradeep R.; Alam, Muhammad A.

2011-06-01

Electromechanical dielectric degradation associated with the hard landing of movable electrode is a technology-inhibiting reliability concern for capacitive RF-MEMS switches. In this letter, we propose two schemes for dynamic soft-landing that obviate the need for external feedback circuitry. Instead, the proposed resistive and capacitive braking schemes can reduce impact velocity significantly without compromising other performance characteristics like pull-in voltage and pull-in time. Resistive braking is achieved by inserting a resistance in series with the voltage source whereas capacitive braking requires patterning of the electrode or the dielectric. Our results have important implications to the design and optimization of reliability aware electrostatically actuated MEMS switches.

Simulation of hydrodynamically interacting particles near a no-slip boundary

NASA Astrophysics Data System (ADS)

Swan, James W.; Brady, John F.

2007-11-01

The dynamics of spherical particles near a single plane wall are computed using an extension of the Stokesian dynamics method that includes long-range many-body and pairwise lubrication interactions between the spheres and the wall in Stokes flow. Extra care is taken to ensure that the mobility and resistance tensors are symmetric, positive, and definite—something which is ineluctable for particles in low-Reynolds-number flows. We discuss why two previous simulation methods for particles near a plane wall, one using multipole expansions and the other using the Rotne-Prager tensor, fail to produce symmetric resistance and mobility tensors. Additionally, we offer some insight on how the Stokesian dynamics paradigm might be extended to study the dynamics of particles in any confining geometry.

Border Malaria Associated with Multidrug Resistance on Thailand-Myanmar and Thailand-Cambodia Borders: Transmission Dynamic, Vulnerability, and Surveillance

PubMed Central

Bhumiratana, Adisak; Intarapuk, Apiradee; Sorosjinda-Nunthawarasilp, Prapa; Maneekan, Pannamas; Koyadun, Surachart

2013-01-01

This systematic review elaborates the concepts and impacts of border malaria, particularly on the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance (MDR) malaria on Thailand-Myanmar and Thailand-Cambodia borders. Border malaria encompasses any complex epidemiological settings of forest-related and forest fringe-related malaria, both regularly occurring in certain transmission areas and manifesting a trend of increased incidence in transmission prone areas along these borders, as the result of interconnections of human settlements and movement activities, cross-border population migrations, ecological changes, vector population dynamics, and multidrug resistance. For regional and global perspectives, this review analyzes and synthesizes the rationales pertaining to transmission dynamics and the vulnerabilities of border malaria that constrain surveillance and control of the world's most MDR falciparum and vivax malaria on these chaotic borders. PMID:23865048

Selectivity of the gas sensor based on the 50%In2O3-50%Ga2O3 thin film in dynamic mode of operation

NASA Astrophysics Data System (ADS)

Demin, I. E.; Kozlov, A. G.

2018-01-01

The article considers the gas sensor with the sensitive layer based on the 50%In2O3 -50%Ga2O3 thin film. The temperature and concentration dependencies of gas-induced resistance response of this sensor and the dynamical dependencies of its resistance response on the test gases in air are investigated. The test gases were ethanol, acetone, ammonia and liquefied petroleum gas. The information parameters of the sensor in the dynamical mode of operation were considered to improve its selectivity. The presented results show that the selectivity of the sensor in this mode may be improved by using the following information parameters: gas-induced resistance response in steady state, activation energy of the response and pre-exponential factor of the temperature dependence of the response time constant.

Dynamics of an HBV Model with Drug Resistance Under Intermittent Antiviral Therapy

NASA Astrophysics Data System (ADS)

Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan

2015-06-01

This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.

Experience with dynamic reinforcement rates decreases resistance to extinction.

PubMed

Craig, Andrew R; Shahan, Timothy A

2016-03-01

The ability of organisms to detect reinforcer-rate changes in choice preparations is positively related to two factors: the magnitude of the change in rate and the frequency with which rates change. Gallistel (2012) suggested similar rate-detection processes are responsible for decreases in responding during operant extinction. Although effects of magnitude of change in reinforcer rate on resistance to extinction are well known (e.g., the partial-reinforcement-extinction effect), effects of frequency of changes in rate prior to extinction are unknown. Thus, the present experiments examined whether frequency of changes in baseline reinforcer rates impacts resistance to extinction. Pigeons pecked keys for variable-interval food under conditions where reinforcer rates were stable and where they changed within and between sessions. Overall reinforcer rates between conditions were controlled. In Experiment 1, resistance to extinction was lower following exposure to dynamic reinforcement schedules than to static schedules. Experiment 2 showed that resistance to presession feeding, a disruptor that should not involve change-detection processes, was unaffected by baseline-schedule dynamics. These findings are consistent with the suggestion that change detection contributes to extinction. We discuss implications of change-detection processes for extinction of simple and discriminated operant behavior and relate these processes to the behavioral-momentum based approach to understanding extinction. © 2016 Society for the Experimental Analysis of Behavior.

In vitro studying corrosion behavior of porous titanium coating in dynamic electrolyte.

PubMed

Chen, Xuedan; Fu, Qingshan; Jin, Yongzhong; Li, Mingtian; Yang, Ruisong; Cui, Xuejun; Gong, Min

2017-01-01

Porous titanium (PT) is considered as a promising biomaterials for orthopedic implants. Besides biocompatibility and mechanical properties, corrosion resistance in physiological environment is the other important factor affecting the long stability of an implant. In order to investigate the corrosion behavior of porous titanium implants in a dynamic physiological environment, a dynamic circle system was designed in this study. Then a titanium-based implant with PT coating was fabricated by plasma spraying. The corrosion resistance of PT samples in flowing 0.9% NaCl solution was evaluated by electrochemical measurements. Commercial pure solid titanium (ST) disc was used as a control. The studies of potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) show that the pores in the PT play a negetive part in corrosion resistance and the flowing electrolyte can increase the corrosive rate of all titanium samples. The results suggest that pore design of titanium implants should pay attention to the effect of dynamic process of a physiological environment on the corrosion behavior of implants. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolution of resistance to anti-cancer therapy during general dosing schedules

PubMed Central

Foo, Jasmine; Michor, Franziska

2009-01-01

Anti-cancer drugs targeted to specific oncogenic pathways have shown promising therapeutic results in the past few years; however, drug resistance remains an important obstacle for these therapies. Resistance to these drugs can emerge due to a variety of reasons including genetic or epigenetic changes which alter the binding site of the drug target, cellular metabolism or export mechanisms. Obtaining a better understanding of the evolution of resistant populations during therapy may enable the design of more effective therapeutic regimens which prevent or delay progression of disease due to resistance. In this paper, we use stochastic mathematical models to study the evolutionary dynamics of resistance under time-varying dosing schedules and pharmacokinetic effects. The populations of sensitive and resistant cells are modeled as multi-type non-homogeneous birth-death processes in which the drug concentration affects the birth and death rates of both the sensitive and resistant cell populations in continuous time. This flexible model allows us to consider the effects of generalized treatment strategies as well as detailed pharmacokinetic phenomena such as drug elimination and accumulation over multiple doses. We develop estimates for the probability of developing resistance and moments of the size of the resistant cell population. With these estimates, we optimize treatment schedules over a subspace of tolerated schedules to minimize the risk of disease progression due to resistance as well as locate ideal schedules for controlling the population size of resistant clones in situations where resistance is inevitable. Our methodology can be used to describe dynamics of resistance arising due to a single (epi)genetic alteration in any tumor type. PMID:20004211

An Investigation of the Elements which Contribute to Statical and Dynamical Stability, and of the Effects of Variation in Those Elements

NASA Technical Reports Server (NTRS)

Klemin, Alexander; Warner, Edward P; Denkinger, George M

1918-01-01

Part 1 gives details of models tested and methods of testing of the Eiffel 36 wing alone and the JN2 aircraft. Characteristics and performance curves for standard JN are included. Part 2 presents a statistical analysis of the following: lift and drag contributed by body and chassis tested without wings; lift and drag contributed by tail, tested without wings; the effect on lift and drift of interference between the wings of a biplane combination; lift and drag contributed by the addition of body, chassis, and tail to a biplane combination; total parasite resistance; effect of varying size of tail, keeping angle of setting constant; effect of varying length of body and size of tail at the same time, keeping constant moment of tail surface about the center of gravity; forces on the tail and the effects of downwash; effect of size and setting of tail on statical longitudinal stability effects of length of body on stability; the effects of the various elements of an airplane on longitudinal stability and the placing of the force vectors. Part 3 presents the fundamental principals of dynamical stability; computations of resistance derivatives; solution of the stability equation; dynamical stability of the Curtiss JN2; tabulation of resistance derivatives; discussion of the resistance derivatives; formation and solution of stability equations; physical conceptions of the resistance derivatives; elements contributing to damping and an investigation of low speed conditions. Part 4 includes a summary of the results of the statistical investigation and a summary of the results for dynamic stability.

Compact modeling of CRS devices based on ECM cells for memory, logic and neuromorphic applications.

PubMed

Linn, E; Menzel, S; Ferch, S; Waser, R

2013-09-27

Dynamic physics-based models of resistive switching devices are of great interest for the realization of complex circuits required for memory, logic and neuromorphic applications. Here, we apply such a model of an electrochemical metallization (ECM) cell to complementary resistive switches (CRSs), which are favorable devices to realize ultra-dense passive crossbar arrays. Since a CRS consists of two resistive switching devices, it is straightforward to apply the dynamic ECM model for CRS simulation with MATLAB and SPICE, enabling study of the device behavior in terms of sweep rate and series resistance variations. Furthermore, typical memory access operations as well as basic implication logic operations can be analyzed, revealing requirements for proper spike and level read operations. This basic understanding facilitates applications of massively parallel computing paradigms required for neuromorphic applications.

Measurement of microchannel fluidic resistance with a standard voltage meter.

PubMed

Godwin, Leah A; Deal, Kennon S; Hoepfner, Lauren D; Jackson, Louis A; Easley, Christopher J

2013-01-03

A simplified method for measuring the fluidic resistance (R(fluidic)) of microfluidic channels is presented, in which the electrical resistance (R(elec)) of a channel filled with a conductivity standard solution can be measured and directly correlated to R(fluidic) using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine R(fluidic) to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ∼40 to 600kPa smm(-3)) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic R(fluidic) measurements were possible in more complex microfluidic designs. Microchannel R(elec) was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Measurement of Microchannel Fluidic Resistance with a Standard Voltage Meter

PubMed Central

Godwin, Leah A.; Deal, Kennon S.; Hoepfner, Lauren D.; Jackson, Louis A.; Easley, Christopher J.

2012-01-01

A simplified method for measuring the fluidic resistance (Rfluidic) of microfluidic channels is presented, in which the electrical resistance (Relec) of a channel filled with a conductivity standard solution can be measured and directly correlated to Rfluidic using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine Rfluidic to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ~40 – 600 kPa s mm−3) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic Rfluidic measurements were possible in more complex microfluidic designs. Microchannel Relec was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems. PMID:23245901

Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability.

PubMed

Zhang, Xiaolin; Jiang, Anmin; Yu, Hao; Xiong, Youyi; Zhou, Guoliang; Qin, Meisong; Dou, Jinfeng; Wang, Jianfei

2016-10-28

Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori ( H. pylori ). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1- N -phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori . Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori , and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.

Ground-truthing electrical resistivity methods in support of submarine groundwater discharge studies: Examples from Hawaii, Washington, and California

USGS Publications Warehouse

Johnson, Cordell; Swarzenski, Peter W.; Richardson, Christina M.; Smith, Christopher G.; Kroeger, Kevin D.; Ganguli, Priya M.

2015-01-01

Rigorous ground-truthing at each field site showed that multi-channel electrcial resistivity techniques can reproduce the scales and dynamics of a seepage field when such data are correctly collected, and when the model inversions are tuned to field site characteristics. Such information can provide a unique perspective on the scales and dynamics of exchange processes within a coastal aquifer—information essential to scientists and resource managers alike.

Response of Metals and Metallic Structures to Dynamic Loading

DTIC Science & Technology

1978-05-01

materials for service by testing under high rates of loading. Impact tests such as the Charpy test, the drop-weight tear test, and the dynamic tear...have clearly shown this for precracked charpy specimens and for the drop-weight tear test. Hence, there is a strong need for additional dynamic...dynamic fracture resistance ( Charpy , dynamic-tear, drop-weight tear test, etc.), normally assures that fracture in dynamically loaded structures is

Defined lipid analogues induce transient channels to facilitate drug-membrane traversal and circumvent cancer therapy resistance

PubMed Central

van Hell, Albert J.; Melo, Manuel N.; van Blitterswijk, Wim J.; Gueth, Dayana M.; Braumuller, Tanya M.; Pedrosa, Lilia R. C.; Song, Ji-Ying; Marrink, Siewert J.; Koning, Gerben A.; Jonkers, Jos; Verheij, Marcel

2013-01-01

Design and efficacy of bioactive drugs is restricted by their (in)ability to traverse cellular membranes. Therapy resistance, a major cause of ineffective cancer treatment, is frequently due to suboptimal intracellular accumulation of the drug. We report a molecular mechanism that promotes trans-membrane movement of a stereotypical, widely used anti-cancer agent to counteract resistance. Well-defined lipid analogues adapt to the amphiphilic drug doxorubicin, when co-inserted into the cell membrane, and assemble a transient channel that rapidly facilitates the translocation of the drug onto the intracellular membrane leaflet. Molecular dynamic simulations unveiled the structure and dynamics of membrane channel assembly. We demonstrate that this principle successfully addresses multi-drug resistance of genetically engineered mouse breast cancer models. Our results illuminate the role of the plasma membrane in restricting the efficacy of established therapies and drug resistance - and provide a mechanism to overcome ineffectiveness of existing and candidate drugs. PMID:23739489

History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment

PubMed Central

Papin, Jason A.

2017-01-01

Antibiotic regimens often include the sequential changing of drugs to limit the development and evolution of resistance of bacterial pathogens. It remains unclear how history of adaptation to one antibiotic can influence the resistance profiles when bacteria subsequently adapt to a different antibiotic. Here, we experimentally evolved Pseudomonas aeruginosa to six 2-drug sequences. We observed drug order–specific effects, whereby adaptation to the first drug can limit the rate of subsequent adaptation to the second drug, adaptation to the second drug can restore susceptibility to the first drug, or final resistance levels depend on the order of the 2-drug sequence. These findings demonstrate how resistance not only depends on the current drug regimen but also the history of past regimens. These order-specific effects may allow for rational forecasting of the evolutionary dynamics of bacteria given knowledge of past adaptations and provide support for the need to consider the history of past drug exposure when designing strategies to mitigate resistance and combat bacterial infections. PMID:28792497

Cardioprotective Properties of Aerobic and Resistance Training Against Myocardial Infarction.

PubMed

Barboza, C A; Souza, G I H; Oliveira, J C M F; Silva, L M; Mostarda, C T; Dourado, P M M; Oyama, L M; Lira, F S; Irigoyen, M C; Rodrigues, B

2016-06-01

We evaluated the effects of aerobic and resistance exercise training on ventricular morphometry and function, physical capacity, autonomic function, as well as on ventricular inflammatory status in trained rats prior to myocardial infarction. Male Wistar rats were divided into the following groups: sedentary+Sham, sedentary+myocardial infarction, aerobic trained+myocardial infarction, and resistance trained+myocardial infarction. Sham and myocardial infarction were performed after training periods. In the days following the surgeries, evaluations were performed. Aerobic training prevents aerobic (to a greater extent) and resistance capacity impairments, ventricular dysfunction, baroreflex sensitivity and autonomic disorders (vagal tonus decrease and sympathetic tonus increase) triggered by myocardial infarction. Resistance training was able to prevent negative changes to aerobic and resistance capacity (to a greater extent) but not to ventricular dysfunction, and it prevented cardiovascular sympathetic increments. Additionally, both types of training reduced left ventricle inflammatory cytokine concentration. Our results suggest that aerobic and, for the first time, dynamic resistance training were able to reduce sympathetic tonus to the heart and vessels, as well as preventing the increase in pro-inflammatory cytokine concentrations in the left ventricle of trained groups. These data emphasizes the positive effects of aerobic and dynamic resistance training on the prevention of the negative changes triggered by myocardial infarction. © Georg Thieme Verlag KG Stuttgart · New York.

Oscillator circuit for use with high loss quartz resonator sensors

DOEpatents

Wessendorf, Otto

1995-01-01

The disclosure is directed to a Lever oscillator for use in high resistance resonator applications, especially for use with quartz resonator sensors. The oscillator is designed to operate over a wide dynamic range of resonator resistance due to damping of the resonator in mediums such as liquids. An oscillator design is presented that allows both frequency and loss (R.sub.m) of the resonator to be determined over a wide dynamic range of resonator loss. The Lever oscillator uses negative feedback in a differential amplifier configuration to actively and variably divide (or leverage) the resonator impedance such that the oscillator can maintain the phase and gain of the loop over a wide range of resonator resistance.

Dependence of the residual surface resistance of superconducting radio frequency cavities on the cooling dynamics around T c

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

Romanenko, A.; Grassellino, A.; Melnychuk, O.

We report a strong effect of the cooling dynamics throughmore » $$T_\\mathrm{c}$$ on the amount of trapped external magnetic flux in superconducting niobium cavities. The effect is similar for fine grain and single crystal niobium and all surface treatments including electropolishing with and without 120$$^\\circ$$C baking and nitrogen doping. Direct magnetic field measurements on the cavity walls show that the effect stems from changes in the flux trapping efficiency: slow cooling leads to almost complete flux trapping and higher residual resistance while fast cooling leads to the much more efficient flux expulsion and lower residual resistance.« less

16 CFR 1203.15 - Positional stability test (roll-off resistance).

Code of Federal Regulations, 2010 CFR

2010-01-01

... any slack. (3) Suspend the dynamic impact system from the helmet by positioning the flexible strap... positions. (3) Dynamic impact apparatus. A dynamic impact apparatus shall be used to apply a shock load to a helmet secured to the test headform. The dynamic impact apparatus shall allow a 4-kg (8.8-lb) drop weight...

In the hunt for genomic markers of metabolic resistance to pyrethroids in the mosquito Aedes aegypti: An integrated next-generation sequencing approach.

PubMed

Faucon, Frederic; Gaude, Thierry; Dusfour, Isabelle; Navratil, Vincent; Corbel, Vincent; Juntarajumnong, Waraporn; Girod, Romain; Poupardin, Rodolphe; Boyer, Frederic; Reynaud, Stephane; David, Jean-Philippe

2017-04-01

The capacity of Aedes mosquitoes to resist chemical insecticides threatens the control of major arbovirus diseases worldwide. Until alternative control tools are widely deployed, monitoring insecticide resistance levels and identifying resistance mechanisms in field mosquito populations is crucial for implementing appropriate management strategies. Metabolic resistance to pyrethroids is common in Aedes aegypti but the monitoring of the dynamics of resistant alleles is impeded by the lack of robust genomic markers. In an attempt to identify the genomic bases of metabolic resistance to deltamethrin, multiple resistant and susceptible populations originating from various continents were compared using both RNA-seq and a targeted DNA-seq approach focused on the upstream regions of detoxification genes. Multiple detoxification enzymes were over transcribed in resistant populations, frequently associated with an increase in their gene copy number. Targeted sequencing identified potential promoter variations associated with their over transcription. Non-synonymous variations affecting detoxification enzymes were also identified in resistant populations. This study not only confirmed the role of gene copy number variations as a frequent cause of the over expression of detoxification enzymes associated with insecticide resistance in Aedes aegypti but also identified novel genomic resistance markers potentially associated with their cis-regulation and modifications of their protein structure conformation. As for gene transcription data, polymorphism patterns were frequently conserved within regions but differed among continents confirming the selection of different resistance factors worldwide. Overall, this study paves the way of the identification of a comprehensive set of genomic markers for monitoring the spatio-temporal dynamics of the variety of insecticide resistance mechanisms in Aedes aegypti.

Joint High Speed Sealift (JHSS) Baseline Shaft & Strut (Model 5653) Series 1: Bare Hull Resistance, Appended Resistance, and Alternative Bow Evaluations

DTIC Science & Technology

2007-08-01

individually for each of the four candidate bows in Appendix B, Figures B13- Bl6 , and collectively in Table B 18. Wave Traces Wave traces along the JHSS BSS... B16 B7. JHSS: BSS, GB, BH, displacement variations, PE test comparisons ............................... B19 B8. JHSS: BSS, bow variations, BH, DES, PE...BSS, EB, dynamic sinkage and pitch ................................................................... B33 B16 . JHSS: BSS, GB, dynamic sinkage and pitch

Mechanistic mathematical modelling of mercaptopurine effects on cell cycle of human acute lymphoblastic leukaemia cells

PubMed Central

Panetta, J C; Evans, W E; Cheok, M H

2006-01-01

The antimetabolite mercaptopurine (MP) is widely used to treat childhood acute lymphoblastic leukaemia (ALL). To study the dynamics of MP on the cell cycle, we incubated human T-cell leukaemia cell lines (Molt-4 sensitive and resistant subline and P12 resistant) with 10 μM MP and measured total cell count, cell cycle distribution, percent viable, percent apoptotic, and percent dead cells serially over 72 h. We developed a mathematical model of the cell cycle dynamics after treatment with MP and used it to show that the Molt-4 sensitive controls had a significantly higher rate of cells entering apoptosis (2.7-fold, P<0.00001) relative to the resistant cell lines. Additionally, when treated with MP, the sensitive cell line showed a significant increase in the rate at which cells enter apoptosis compared to its controls (2.4-fold, P<0.00001). Of note, the resistant cell lines had a higher rate of antimetabolite incorporation into the DNA of viable cells (>1.4-fold, P<0.01). Lastly, in contrast to the other cell lines, the Molt-4 resistant subline continued to cycle, though at a rate slower relative to its control, rather than proceed to apoptosis. This led to a larger S-phase block in the Molt-4 resistant cell line, but not a higher rate of cell death. Gene expression of apoptosis, cell cycle, and repair genes were consistent with mechanistic dynamics described by the model. In summary, the mathematical model provides a quantitative assessment to compare the cell cycle effects of MP in cells with varying degrees of MP resistance. PMID:16333308

The effect of spring pads in the secondary suspension of railway vehicles on bogie yaw resistance

NASA Astrophysics Data System (ADS)

Michálek, Tomáš; Zelenka, Jaromír

2015-12-01

This paper deals with properties of bogie yaw resistance of an electric locomotive with secondary suspension consisting of flexi-coil springs supplemented with tilting spring pads. Transversal stiffness of a sample of a spring/pad assembly was measured on a dynamic test stand of the University of Pardubice (Czech Republic) and the results were applied into a multi-body model of the locomotive created in the simulation tool 'SJKV'. On the basis of the simulation results, a detailed analysis of the bogie yaw resistance was performed in order to explain the effect in dynamic behaviour of the locomotive when the moment against bogie rotation (and therefore the distribution of guiding forces on individual wheels, as well) is influenced with the vehicle speed in a certain curve. Results of this analysis show that the application of suspension elements with strongly directionally dependent transversal stiffness into the secondary suspension can just lead to a dependency of the bogie yaw resistance on cant deficiency, i.e. on the vehicle speed in curve. This fact has wide consequences on the vehicle dynamics (especially on the guiding behaviour of the vehicle in curves) and it also points out that the current method of evaluation of the bogie yaw resistance according to relevant standards, which is related with assessment of the quasistatic safety of a railway vehicle against derailment, is not objective enough.

Biological soil crusts across disturbance–recovery scenarios: effect of grazing regime on community dynamics.

PubMed

Concostrina-Zubiri, L; Huber-Sannwald, E; Martínez, I; Flores Flores, J L; Reyes-Agüero, J A; Escude, A; Belnap, J

Grazing represents one of the most common disturbances in drylands worldwide, affecting both ecosystem structure and functioning. Despite the efforts to understand the nature and magnitude of grazing effects on ecosystem components and processes, contrasting results continue to arise. This is particularly remarkable for the biological soil crust (BSC) communities (i.e., cyanobacteria, lichens, and bryophytes), which play an important role in soil dynamics. Here we evaluated simultaneously the effect of grazing impact on BSC communities (resistance) and recovery after livestock exclusion (resilience) in a semiarid grassland of Central Mexico. In particular, we examined BSC species distribution, species richness, taxonomical group cover (i.e., cyanobacteria, lichen, bryophyte), and composition along a disturbance gradient with different grazing regimes (low, medium, high impact) and along a recovery gradient with differently aged livestock exclosures (short-, medium-, long-term exclusion). Differences in grazing impact and time of recovery from grazing both resulted in slight changes in species richness; however, there were pronounced shifts in species composition and group cover. We found we could distinguish four highly diverse and dynamic BSC species groups: (1) species with high resistance and resilience to grazing, (2) species with high resistance but low resilience, (3) species with low resistance but high resilience, and (4) species with low resistance and resilience. While disturbance resulted in a novel diversity configuration, which may profoundly affect ecosystem functioning, we observed that 10 years of disturbance removal did not lead to the ecosystem structure found after 27 years of recovery. These findings are an important contribution to our understanding of BCS dynamics from a species and community perspective placed in a land use change context.

Biological soil crusts across disturbance-recovery scenarios: effect of grazing regime on community dynamics

USGS Publications Warehouse

Concostrina-Zubiri, L.; Huber-Sannwald, E.; Martínez, I.; Flores Flores, J. L.; Reyes-Agüero, J. A.; Escudero, A.; Belnap, Jayne

2014-01-01

Grazing represents one of the most common disturbances in drylands worldwide, affecting both ecosystem structure and functioning. Despite the efforts to understand the nature and magnitude of grazing effects on ecosystem components and processes, contrasting results continue to arise. This is particularly remarkable for the biological soil crust (BSC) communities (i.e., cyanobacteria, lichens, and bryophytes), which play an important role in soil dynamics. Here we evaluated simultaneously the effect of grazing impact on BSC communities (resistance) and recovery after livestock exclusion (resilience) in a semiarid grassland of Central Mexico. In particular, we examined BSC species distribution, species richness, taxonomical group cover (i.e., cyanobacteria, lichen, bryophyte), and composition along a disturbance gradient with different grazing regimes (low, medium, high impact) and along a recovery gradient with differently aged livestock exclosures (short-, medium-, long-term exclusion). Differences in grazing impact and time of recovery from grazing both resulted in slight changes in species richness; however, there were pronounced shifts in species composition and group cover. We found we could distinguish four highly diverse and dynamic BSC species groups: (1) species with high resistance and resilience to grazing, (2) species with high resistance but low resilience, (3) species with low resistance but high resilience, and (4) species with low resistance and resilience. While disturbance resulted in a novel diversity configuration, which may profoundly affect ecosystem functioning, we observed that 10 years of disturbance removal did not lead to the ecosystem structure found after 27 years of recovery. These findings are an important contribution to our understanding of BCS dynamics from a species and community perspective placed in a land use change context.

Pseudo-polar drive patterns for brain electrical impedance tomography.

PubMed

Shi, Xuetao; Dong, Xiuzhen; Shuai, Wanjun; You, Fusheng; Fu, Feng; Liu, Ruigang

2006-11-01

Brain electrical impedance tomography (EIT) is a difficult task as brain tissues are enclosed by the skull of high resistance and cerebrospinal fluid (CSF) of low resistance, which makes internal resistivity information more difficult to extract. In order to seek a single source drive pattern that is more suitable for brain EIT, we built a more realistic experimental setting that simulates a head with the resistivity of the scalp, skull, CSF and brain, and compared the performance of adjacent, cross, polar and pseudo-polar drive patterns in terms of the boundary voltage dynamic range, independent measurement number, total boundary voltage changes and anti-noise performance based on it. The results demonstrate that the pseudo-polar drive pattern is optimal in all the aspects except for the dynamic range. The polar and cross drive patterns come next, and the adjacent drive pattern is the worst. Therefore, the pseudo-polar drive pattern should be chosen for brain EIT.

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

PubMed Central

Quinton, Lee J.; Mizgerd, Joseph P.

2015-01-01

Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps. PMID:25148693

Plasticity, dynamics, and inhibition of emerging tetracycline-resistance enzymes

PubMed Central

Park, Jooyoung; Gasparrini, Andrew J.; Reck, Margaret R.; Symister, Chanez T.; Elliott, Jennifer L.; Vogel, Joseph P.; Wencewicz, Timothy A.; Dantas, Gautam; Tolia, Niraj H.

2017-01-01

While tetracyclines are an important class of antibiotics in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently-discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes with a high potential for broad dissemination. Here, we show tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a novel tetracycline/tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics. PMID:28481346

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes.

PubMed

Park, Jooyoung; Gasparrini, Andrew J; Reck, Margaret R; Symister, Chanez T; Elliott, Jennifer L; Vogel, Joseph P; Wencewicz, Timothy A; Dantas, Gautam; Tolia, Niraj H

2017-07-01

Although tetracyclines are an important class of antibiotics for use in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored, despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes that have a high potential for broad dissemination. Here, we show that tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a new tetracycline and tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics.

Cooperative Bacterial Growth Dynamics Predict the Evolution of Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Artemova, Tatiana; Gerardin, Ylaine; Hsin-Jung Li, Sophia; Gore, Jeff

2011-03-01

Since the discovery of penicillin, antibiotics have been our primary weapon against bacterial infections. Unfortunately, bacteria can gain resistance to penicillin by acquiring the gene that encodes beta-lactamase, which inactivates the antibiotic. However, mutations in this gene are necessary to degrade the modern antibiotic cefotaxime. Understanding the conditions that favor the spread of these mutations is a challenge. Here we show that bacterial growth in beta-lactam antibiotics is cooperative and that the nature of this growth determines the conditions in which resistance evolves. Quantitative analysis of the growth dynamics predicts a peak in selection at very low antibiotic concentrations; competition between strains confirms this prediction. We also find significant selection at higher antibiotic concentrations, close to the minimum inhibitory concentrations of the strains. Our results argue that an understanding of the evolutionary forces that lead to antibiotic resistance requires a quantitative understanding of the evolution of cooperation in bacteria.

Effects of Pharmacokinetic Processes and Varied Dosing Schedules on the Dynamics of Acquired Resistance to Erlotinib in EGFR-Mutant Lung Cancer

PubMed Central

Foo, Jasmine; Chmielecki, Juliann; Pao, William; Michor, Franziska

2013-01-01

Introduction Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which effectively targets EGFR-mutant driven non–small-cell lung cancer. However, the evolution of acquired resistance because of a second-site mutation (T790M) within EGFR remains an obstacle to successful treatment. Methods We used mathematical modeling and available clinical trial data to predict how different pharmacokinetic parameters (fast versus slow metabolism) and dosing schedules (low dose versus high dose; missed doses with and without make-up doses) might affect the evolution of T790M-mediated resistance in mixed populations of tumor cells. Results We found that high-dose pulses with low-dose continuous therapy impede the development of resistance to the maximum extent, both pre- and post-emergence of resistance. The probability of resistance is greater in fast versus slow drug metabolizers, suggesting a potential mechanism, unappreciated to date, influencing acquired resistance in patients. In case of required dose modifications because of toxicity, little difference is observed in terms of efficacy and resistance dynamics between the standard daily dose (150 mg/d) and 150 mg/d alternating with 100 mg/d. Missed doses are expected to lead to resistance faster, even if make-up doses are attempted. Conclusions For existing and new kinase inhibitors, this novel framework can be used to rationally and rapidly design optimal dosing strategies to minimize the development of acquired resistance. PMID:22982659

A new insight into arable weed adaptive evolution: mutations endowing herbicide resistance also affect germination dynamics and seedling emergence

PubMed Central

Délye, Christophe; Menchari, Yosra; Michel, Séverine; Cadet, Émilie; Le Corre, Valérie

2013-01-01

Background and Aims Selective pressures exerted by agriculture on populations of arable weeds foster the evolution of adaptive traits. Germination and emergence dynamics and herbicide resistance are key adaptive traits. Herbicide resistance alleles can have pleiotropic effects on a weed's life cycle. This study investigated the pleiotropic effects of three acetyl-coenzyme A carboxylase (ACCase) alleles endowing herbicide resistance on the seed-to-plant part of the life cycle of the grass weed Alopecurus myosuroides. Methods In each of two series of experiments, A. myosuroides populations with homogenized genetic backgrounds and segregating for Leu1781, Asn2041 or Gly2078 ACCase mutations which arose independently were used to compare germination dynamics, survival in the soil and seedling pre-emergence growth among seeds containing wild-type, heterozygous and homozygous mutant ACCase embryos. Key Results Asn2041 ACCase caused no significant effects. Gly2078 ACCase major effects were a co-dominant acceleration in seed germination (1·25- and 1·10-fold decrease in the time to reach 50 % germination (T50) for homozygous and heterozygous mutant embryos, respectively). Segregation distortion against homozygous mutant embryos or a co-dominant increase in fatal germination was observed in one series of experiments. Leu1781 ACCase major effects were a co-dominant delay in seed germination (1·41- and 1·22-fold increase in T50 for homozygous and heterozygous mutant embryos, respectively) associated with a substantial co-dominant decrease in fatal germination. Conclusions Under current agricultural systems, plants carrying Leu1781 or Gly2078 ACCase have a fitness advantage conferred by herbicide resistance that is enhanced or counterbalanced, respectively, by direct pleiotropic effects on the plant phenology. Pleiotropic effects associated with mutations endowing herbicide resistance undoubtedly play a significant role in the evolutionary dynamics of herbicide resistance in weed populations. Mutant ACCase alleles should also prove useful to investigate the role played by seed storage lipids in the control of seed dormancy and germination. PMID:23393095

Ferroelectric domain switching dynamics and memristive behaviors in BiFeO3-based magnetoelectric heterojunctions

NASA Astrophysics Data System (ADS)

Huang, Weichuan; Liu, Yukuai; Luo, Zhen; Hou, Chuangming; Zhao, Wenbo; Yin, Yuewei; Li, Xiaoguang

2018-06-01

The ferroelectric domain reversal dynamics and the corresponding resistance switching as well as the memristive behaviors in epitaxial BiFeO3 (BFO, ~150 nm) based multiferroic heterojunctions were systematically investigated. The ferroelectric domain reversal dynamics could be described by the nucleation-limited-switching model with the Lorentzian distribution of logarithmic domain-switching times. By engineering the domain states, multi and even continuously tunable resistances states, i.e. memristive states, could be non-volatilely achieved. The resistance switching speed can be as fast as 30 ns in the BFO-based multiferroic heterojunctions with a write voltage of ~20 V. By reducing the thickness of BFO, the La0.6Sr0.4MnO3/BFO (~5 nm)/La0.6Sr0.4MnO3 multiferroic tunnel junction (MFTJ) shows an even a quicker switching speed (20 ns) with a much lower operation voltage (~4 V). Importantly, the MFTJ exhibits a tunable interfacial magnetoelectric coupling related to the ferroelectric domain switching dynamics. These findings enrich the potential applications of multiferroic BFO based devices in high-speed, low-power, and high-density memories as well as future neuromorphic computational architectures.

Molecular Dynamics Study of HIV-1 RT-DNA-Nevirapine Complexes Explains NNRTI Inhibition, and Resistance by Connection Mutations

PubMed Central

Vijayan, R.S.K.; Arnold, Eddy; Das, Kalyan

2015-01-01

HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that is targeted by nucleoside analogs (NRTIs) and nonnucleoside inhibitors (NNRTIs). NNRTIs are allosteric inhibitors of RT, and constitute an integral part of the highly active antiretroviral therapy (HAART) regimen. Under selective pressure, HIV-1 acquires resistance against NNRTIs primarily by selecting mutations around the NNRTI pocket. Complete RT sequencing of clinical isolates revealed that spatially distal mutations arising in connection and the RNase H domain also confer NNRTI resistance and contribute to NRTI resistance. However, the precise structural mechanism by which the connection domain mutations confer NNRTI resistance is poorly understood. We performed 50-ns MD simulations, followed by essential dynamics, free-energy landscape analyses and network analyses of RT-DNA, RT-DNA-nevirapine, and N348I/T369I mutant RT-DNA-nevirapine complexes. MD simulation studies revealed altered global motions and restricted conformational landscape of RT upon nevirapine binding. Analysis of protein structure network parameters demonstrated a dissortative hub pattern in the RT-DNA complex and an assortative hub pattern in the RT-DNA-nevirapine complex suggesting enhanced rigidity of RT upon nevirapine binding. The connection subdomain mutations N348I/T369I did not induce any significant structural change; rather, these mutations modulate the conformational dynamics and alter the long-range allosteric communication network between the connection subdomain and NNRTI pocket. Insights from the present study provide a structural basis for the biochemical and clinical findings on drug resistance caused by the connection and RNase H mutations. PMID:24174331

A membrane computing simulator of trans-hierarchical antibiotic resistance evolution dynamics in nested ecological compartments (ARES).

PubMed

Campos, Marcelino; Llorens, Carlos; Sempere, José M; Futami, Ricardo; Rodriguez, Irene; Carrasco, Purificación; Capilla, Rafael; Latorre, Amparo; Coque, Teresa M; Moya, Andres; Baquero, Fernando

2015-08-05

Antibiotic resistance is a major biomedical problem upon which public health systems demand solutions to construe the dynamics and epidemiological risk of resistant bacteria in anthropogenically-altered environments. The implementation of computable models with reciprocity within and between levels of biological organization (i.e. essential nesting) is central for studying antibiotic resistances. Antibiotic resistance is not just the result of antibiotic-driven selection but more properly the consequence of a complex hierarchy of processes shaping the ecology and evolution of the distinct subcellular, cellular and supra-cellular vehicles involved in the dissemination of resistance genes. Such a complex background motivated us to explore the P-system standards of membrane computing an innovative natural computing formalism that abstracts the notion of movement across membranes to simulate antibiotic resistance evolution processes across nested levels of micro- and macro-environmental organization in a given ecosystem. In this article, we introduce ARES (Antibiotic Resistance Evolution Simulator) a software device that simulates P-system model scenarios with five types of nested computing membranes oriented to emulate a hierarchy of eco-biological compartments, i.e. a) peripheral ecosystem; b) local environment; c) reservoir of supplies; d) animal host; and e) host's associated bacterial organisms (microbiome). Computational objects emulating molecular entities such as plasmids, antibiotic resistance genes, antimicrobials, and/or other substances can be introduced into this framework and may interact and evolve together with the membranes, according to a set of pre-established rules and specifications. ARES has been implemented as an online server and offers additional tools for storage and model editing and downstream analysis. The stochastic nature of the P-system model implemented in ARES explicitly links within and between host dynamics into a simulation, with feedback reciprocity among the different units of selection influenced by antibiotic exposure at various ecological levels. ARES offers the possibility of modeling predictive multilevel scenarios of antibiotic resistance evolution that can be interrogated, edited and re-simulated if necessary, with different parameters, until a correct model description of the process in the real world is convincingly approached. ARES can be accessed at http://gydb.org/ares.

Dynamics of graphite fiber intercalation: In situ resistivity measurements with a four point probe

NASA Technical Reports Server (NTRS)

Jaworske, D. A.

1984-01-01

The dynamics of ferric chloride intercalation of single graphite fibers were studied, in situ, using a four point dc bridge. Measurements before, during and after the intercalation showed that the intercalation occurred within minutes at 200 C. Changes in fiber resistivity after exposure to air suggested hydration of the graphite intercalation compound. Deintercalation of the ferric chloride was initiated at temperatures in excess of 400 C. cycling the intercalant into and out of the graphite fiber gave no improvements in fiber resistivity. The activation energy of the ferric chloride intercalation reaction was found to be 17 + or - 4 kcal/mol 1 consistent with the concept of a preliminary nucleation step in the intercalation reaction.

Numerical Simulation on the Dynamic Splitting Tensile Test of reinforced concrete

NASA Astrophysics Data System (ADS)

Zhao, Zhuan; Jia, Haokai; Jing, Lin

2018-03-01

The research for crack resistance was of RC was based on the split Hopkinson bar and numerical simulate software LS-DYNA3D. In the research, the difference of dynamic splitting failure modes between plane concrete and reinforced concrete were completed, and the change rule of tensile stress distribution with reinforcement ratio was studied; also the effect rule with the strain rate and the crack resistance was also discussed by the radial tensile stress time history curve of RC specimen under different loading speeds. The results shows that the reinforcement in the concrete can impede the crack extension, defer the failure time of concrete, increase the tension intensity of concrete; with strain rate of concrete increased, the crack resistance of RC increased.

Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India.

PubMed

Lewnard, Joseph A; Townsend, Jeffrey P

2016-12-20

Immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. However, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. Plague presents an optimal system for interrogating such couplings: Yersinia pestis transmission exerts intense selective pressure driving the local persistence of disease resistance among its wildlife hosts in endemic areas. Investigations undertaken in colonial India after the introduction of plague in 1896 suggest that, only a decade after plague arrived, a heritable, plague-resistant phenotype had become prevalent among commensal rats of cities undergoing severe plague epidemics. To understand the possible evolutionary basis of these observations, we developed a mathematical model coupling environmentally forced plague dynamics with evolutionary selection of rats, capitalizing on extensive archival data from Indian Plague Commission investigations. Incorporating increased plague resistance among rats as a consequence of intense natural selection permits the model to reproduce observed changes in seasonal epidemic patterns in several cities and capture experimentally observed associations between climate and flea population dynamics in India. Our model results substantiate Victorian era claims of host evolution based on experimental observations of plague resistance and reveal the buffering effect of such evolution against environmental drivers of transmission. Our analysis shows that historical datasets can yield powerful insights into the transmission dynamics of reemerging disease agents with which we have limited contemporary experience to guide quantitative modeling and inference.

Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India

PubMed Central

Lewnard, Joseph A.

2016-01-01

Immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. However, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. Plague presents an optimal system for interrogating such couplings: Yersinia pestis transmission exerts intense selective pressure driving the local persistence of disease resistance among its wildlife hosts in endemic areas. Investigations undertaken in colonial India after the introduction of plague in 1896 suggest that, only a decade after plague arrived, a heritable, plague-resistant phenotype had become prevalent among commensal rats of cities undergoing severe plague epidemics. To understand the possible evolutionary basis of these observations, we developed a mathematical model coupling environmentally forced plague dynamics with evolutionary selection of rats, capitalizing on extensive archival data from Indian Plague Commission investigations. Incorporating increased plague resistance among rats as a consequence of intense natural selection permits the model to reproduce observed changes in seasonal epidemic patterns in several cities and capture experimentally observed associations between climate and flea population dynamics in India. Our model results substantiate Victorian era claims of host evolution based on experimental observations of plague resistance and reveal the buffering effect of such evolution against environmental drivers of transmission. Our analysis shows that historical datasets can yield powerful insights into the transmission dynamics of reemerging disease agents with which we have limited contemporary experience to guide quantitative modeling and inference. PMID:27791071

In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

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

Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au; De Souza, David P.; Risis, Steve

Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine themore » evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-{sup 13}C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac insulin resistance. • Clamp measures were compared to a dynamic metabolomics approach. • The clamp revealed the presence of cardiac insulin resistance after 3 weeks of HFD. • Cardiac glucose metabolism was not affected by HFD during an oral glucose challenge.« less

Lower limb explosive strength capacity in elderly women: effects of resistance training and healthy diet.

PubMed

Edholm, Peter; Strandberg, Emelie; Kadi, Fawzi

2017-07-01

The effects of 24 wk of resistance training combined with a healthy diet on lower limb explosive strength capacity were investigated in a population of healthy elderly women. Participants ( n = 63; 67.5 ± 0.4 yr) were randomized into three groups; resistance training (RT), resistance training and healthy diet (RT-HD), and control (CON). Progressive resistance training was performed at a load of 75-85% one-repetition maximum. A major adjustment in the healthy dietary approach was an n-6/n-3 polyunsaturated fatty acid (PUFA) ratio below 2. Lower limb maximal strength, explosive force capacity during dynamic and isometric movements, whole body lean mass, and physical function were assessed. Whole body lean mass significantly increased by 1.5 ± 0.5% in RT-HD only. Isometric strength performance during knee extension as well as the performance in the five sit-to-stand and single-leg-stance tests increased similarly in RT and RT-HD. Improvements in dynamic peak power and time to reach peak power (i.e shorter time) during knee extension occurred in both RT (+15.7 ± 2.6 and -11.0 ± 3.8%, respectively) and RT-HD (+24.6 ± 2.6 and -20.3 ± 2.7%, respectively); however, changes were significantly larger in RT-HD. Similarly, changes in peak force and rate of force development during squat jump were higher in RT-HD (+58.5 ± 8.4 and +185.4 ± 32.9%, respectively) compared with RT (+35.7 ± 6.9 and +105.4 ± 22.4%, respectively). In conclusion, a healthy diet rich in n-3 PUFA can optimize the effects of resistance training on dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women. NEW & NOTEWORTHY Age-related decline in lower limb explosive strength leads to impaired ability to perform daily living tasks. The present randomized controlled trial demonstrates that a healthy diet rich in n-3 polyunsaturated fatty acid (n-3 PUFA) enhances resistance training-induced gains in dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women. This supports the use of strategies combining resistance training and dietary changes to mitigate the decline in explosive strength capacity in older adults. Copyright © 2017 the American Physiological Society.

Specific balance training included in an endurance-resistance exercise program improves postural balance in elderly patients undergoing haemodialysis.

PubMed

Frih, Bechir; Mkacher, Wajdi; Jaafar, Hamdi; Frih, Ameur; Ben Salah, Zohra; El May, Mezry; Hammami, Mohamed

2018-04-01

The purpose of this study was to evaluate the effects of 6 months of specific balance training included in endurance-resistance program on postural balance in haemodialysis (HD) patients. Forty-nine male patients undergoing HD were randomly assigned to an intervention group (balance training included in an endurance-resistance training, n = 26) or a control group (resistance-endurance training only, n = 23). Postural control was assessed using six clinical tests; Timed Up and Go test, Tinetti Mobility Test, Berg Balance Scale, Unipodal Stance test, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scale. All balance measures increased significantly after the period of rehabilitation training in the intervention group. Only the Timed Up and Go, Berg Balance Scale, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scores were improved in the control group. The ranges of change in these tests were greater in the balance training group. In HD patients, specific balance training included in a usual endurance-resistance training program improves static and dynamic balance better than endurance-resistance training only. Implications for rehabilitation Rehabilitation using exercise in haemodialysis patients improved global mobility and functional abilities. Specific balance training included in usual endurance resistance training program could lead to improved static and dynamic balance.

The Model of Motivational Dynamics in Sport: Resistance to Peer Influence, Behavioral Engagement and Disaffection, Dispositional Coping, and Resilience.

PubMed

Nicholls, Adam R; Morley, David; Perry, John L

2015-01-01

The Model of Motivational Dynamics (MMD; Skinner and Pitzer, 2012) infers that peers influence behavioral engagement levels, which in turn is linked to coping and resilience. Scholars, however, are yet to test the MMD among an athletic population. The purpose of this paper was to assess an a priori model that included key constructs from the MMD, such as resistance to peer influence, behavioral engagement and disaffection, coping, and resilience among athletes. Three hundred and fifty-one athletes (male n = 173, female n = 178; M age = 16.15 years) completed a questionnaire that measured each construct. Our results provide support for the model. In particular, there were positive paths between resistance to peer influence and behavioral engagement, behavioral engagement and task-oriented coping, and task-oriented coping with resilience. There was also a positive path between resilience and resistance to peer influence, but a negative path from resistance to peer influence to behavioral disaffection. Due to the reported benefits of enhancing resistance to peer influence and behavioral engagement, researchers could devise sport specific interventions to maximize athletes' scores in these constructs.

J-R fracture characteristics of ferritic steels for RPVs and RCS piping of nuclear power plants

NASA Astrophysics Data System (ADS)

Yoon, Ji-Hyun; Lee, Bong-Sang; Hong, Jun-Hwa

2001-10-01

J-R fracture resistance tests have been performed on 3 heats of SA508-Gr.3 nuclear reactor pressure vessel (RPV) steel as well as 2 heats of SA516-Gr.70 and a heat of SA508-Gr.1a steels for nuclear reactor coolant system (RCS) piping. For the latter two steels, dynamic in addition to static J-R fracture resistances were investigated. From the test results of the SA508-Gr.3 steels, the J-R fracture resistance was superior in the following order: Si-killing steel, modified VCD steel and VCD steel. Microstructural analyses were carried out to correlate J-R fracture resistances with microstructural characteristics. According to the test results for SA508-Gr.1a and SA516-Gr.70 steels, all of the tested steels showed steep drops in fracture resistance at certain temperature and loading rate combinations. One heat of SA516-Gr.70 steel was very sensitive to dynamic strain aging and its fracture resistance was significantly low. It was concluded that microstructural and chemical factors affect the J-R fracture and DSA characteristics of SA516-Gr.70 steels.

Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance

PubMed Central

Azam, Mohammad; Nardi, Valentina; Shakespeare, William C.; Metcalf, Chester A.; Bohacek, Regine S.; Wang, Yihan; Sundaramoorthi, Raji; Sliz, Piotr; Veach, Darren R.; Bornmann, William G.; Clarkson, Bayard; Dalgarno, David C.; Sawyer, Tomi K.; Daley, George Q.

2006-01-01

Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukemia. Many mutations favor active kinase conformations that preclude imatinib binding. Because the active forms of ABL and SRC resemble one another, we tested two dual SRC-ABL kinase inhibitors, AP23464 and PD166326, against 58 imatinib-resistant (IMR) BCR/ABL kinase variants. Both compounds potently inhibit most IMR variants, and in vitro drug selection demonstrates that active (AP23464) and open (PD166326) conformation-specific compounds are less susceptible to resistance than imatinib. Combinations of inhibitors suppressed essentially all resistance mutations, with the notable exception of T315I. Guided by mutagenesis studies and molecular modeling, we designed a series of AP23464 analogues to target T315I. The analogue AP23846 inhibited both native and T315I variants of BCR/ABL with submicromolar potency but showed nonspecific cellular toxicity. Our data illustrate how conformational dynamics of the ABL kinase accounts for the activity of dual SRC-ABL inhibitors against IMR-mutants and provides a rationale for combining conformation specific inhibitors to suppress resistance. PMID:16754879

Temporal Dynamics and Spatial Variation of Azoxystrobin and Propiconazole Resistance in Zymoseptoria tritici: A Hierarchical Survey of Commercial Winter Wheat Fields in the Willamette Valley, Oregon.

PubMed

Hagerty, Christina H; Anderson, Nicole P; Mundt, Christopher C

2017-03-01

Fungicide resistance can cause disease control failure in agricultural systems, and is particularly concerning with Zymoseptoria tritici, the causal agent of Septoria tritici blotch of wheat. In North America, the first quinone outside inhibitor resistance in Z. tritici was discovered in the Willamette Valley of Oregon in 2012, which prompted this hierarchical survey of commercial winter wheat fields to monitor azoxystrobin- and propiconazole-resistant Z. tritici. Surveys were conducted in June 2014, January 2015, May 2015, and January 2016. The survey was organized in a hierarchical scheme: regions within the Willamette Valley, fields within the region, transects within the field, and samples within the transect. Overall, frequency of azoxystrobin-resistant isolates increased from 63 to 93% from June 2014 to January 2016. Resistance to azoxystrobin increased over time even within fields receiving no strobilurin applications. Propiconazole sensitivity varied over the course of the study but, overall, did not significantly change. Sensitivity to both fungicides showed no regional aggregation within the Willamette Valley. Greater than 80% of spatial variation in fungicide sensitivity was at the smallest hierarchical scale (within the transect) of the survey for both fungicides, and the resistance phenotypes were randomly distributed within sampled fields. Results suggest a need for a better understanding of the dynamics of fungicide resistance at the landscape level.

Structure-based methods to predict mutational resistance to diarylpyrimidine non-nucleoside reverse transcriptase inhibitors.

PubMed

Azeem, Syeda Maryam; Muwonge, Alecia N; Thakkar, Nehaben; Lam, Kristina W; Frey, Kathleen M

2018-01-01

Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance. In order to aid drug design efforts, it would be efficient and cost effective to pre-evaluate NNRTI compounds in development using a structure-based computational approach. As proof of concept, we applied a residue scan and molecular dynamics strategy using RT crystal structures to predict mutations that confer resistance to DAPYs rilpivirine, etravirine, and investigational microbicide dapivirine. Our predictive values, changes in affinity and stability, are correlative with fold-resistance data for several RT mutants. Consistent with previous studies, mutation K101P is predicted to confer high-level resistance to DAPYs. These findings were further validated using structural analysis, molecular dynamics, and an enzymatic reverse transcription assay. Our results confirm that changes in affinity and stability for mutant complexes are predictive parameters of resistance as validated by experimental and clinical data. In future work, we believe that this computational approach may be useful to predict resistance mutations for inhibitors in development. Published by Elsevier Inc.

Influence of chemical reactions on the nonlinear dynamics of dissipative flows

NASA Astrophysics Data System (ADS)

Karimov, A. R.; Korshunov, A. M.; Beklemishev, V. V.

2015-08-01

The nonlinear dynamics of resistive flow with a chemical reaction is studied. Proceeding from the Lagrangian description, the influence of a chemical reaction on the development of fluid singularities is considered.

Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

PubMed Central

Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo; Toft, Nils; Matthews, Louise

2014-01-01

High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma concentration profiles of tetracycline. All dosing regimens result in a clear growth advantage for resistant strains. Short treatment duration was found to be preferable, since it allowed less time for resistant strains to outcompete the susceptible ones. Dosing frequency appeared to be ineffective at reducing the resistance levels. The number of competing strains had no apparent effect on the resistance level during treatment, but possession of fewer strains reduced the time to reach equilibrium after the end of treatment. To sum up, epidemiological parameters may have more profound influence on growth dynamics than dosing regimens and should be considered when designing improved treatment protocols. PMID:25547361

Embedded data collector (EDC) phase II load and resistance factor design (LRFD) : [summary].

DOT National Transportation Integrated Search

2015-07-01

Piles that support bridge structures are designed for the specific site characteristics and loads : that the piles are expected to bear. In Florida, driven piles are monitored during installation : (dynamically tested) to assess resistance, com...

Simulations of CYP51A from Aspergillus fumigatus in a model bilayer provide insights into triazole drug resistance.

PubMed

Nash, Anthony; Rhodes, Johanna

2018-04-01

Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B. The derived structures, wild type, and L98H mutant are positioned within a lipid membrane bilayer and subjected to molecular dynamics simulations in order improve the accuracy of both models. The structural analysis from our simulations suggests a decrease in active site surface from the formation of hydrogen bonds between the histidine substitution and neighboring polar side chains, potentially preventing the binding of azole drugs. This study yields a biologically relevant structure and set of dynamics of the A. fumigatus Lanosterol 14 alpha-demethylase enzyme and provides further insight into azole antifungal drug resistance.

A Bactericidal Guanidinomethyl Biaryl That Alters the Dynamics of Bacterial FtsZ Polymerization

PubMed Central

Kaul, Malvika; Parhi, Ajit K.; Zhang, Yongzheng; LaVoie, Edmond J.; Tuske, Steve; Arnold, Eddy; Kerrigan, John E.; Pilch, Daniel S.

2014-01-01

The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4′-(tert-butyl)-[1,1′-biphenyl]-3-yl)methyl)guanidine} that targets the bacterial cell division protein FtsZ. In vitro studies with various bacterial FtsZ proteins reveal that the compound alters the dynamics of FtsZ self-polymerization via a stimulatory mechanism, while minimally impacting the polymerization of tubulin, the closest mammalian homologue of FtsZ. The FtsZ binding site of the compound is identified through a combination of computational and mutational approaches. The compound exhibits a broad spectrum of bactericidal activity, including activity against the multidrug-resistant pathogens methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), while also exhibiting a minimal potential to induce resistance. Taken together, our results highlight the compound as a promising new FtsZ-targeting bactericidal agent. PMID:23050700

Nonlinear Contact Effects in Staggered Thin-Film Transistors

NASA Astrophysics Data System (ADS)

Fischer, Axel; Zündorf, Hilke; Kaschura, Felix; Widmer, Johannes; Leo, Karl; Kraft, Ulrike; Klauk, Hagen

2017-11-01

The static and dynamic electrical characteristics of thin-film transistors (TFTs) are often limited by the parasitic contact resistances, especially for TFTs with a small channel length. For the smallest possible contact resistance, the staggered device architecture has a general advantage over the coplanar architecture of a larger injection area. Since the charge transport occurs over an extended area, it is inherently more difficult to develop an accurate analytical device model for staggered TFTs. Most analytical models for staggered TFTs, therefore, assume that the contact resistance is linear, even though this is commonly accepted not to be the case. Here, we introduce a semiphenomenological approach to accurately fit experimental data based on a highly discretized equivalent network circuit explicitly taking into account the inherent nonlinearity of the contact resistance. The model allows us to investigate the influence of nonlinear contact resistances on the static and dynamic performance of staggered TFTs for different contact layouts with a relatively short computation time. The precise extraction of device parameters enables us to calculate the transistor behavior as well as the potential for optimization in real circuits.

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

PubMed

Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Applicability of dynamic membrane technology in anaerobic membrane bioreactors.

PubMed

Ersahin, Mustafa Evren; Ozgun, Hale; Tao, Yu; van Lier, Jules B

2014-01-01

This study investigated the applicability of dynamic membrane technology in anaerobic membrane bioreactors for the treatment of high strength wastewaters. A monofilament woven fabric was used as support material for dynamic membrane formation. An anaerobic dynamic membrane bioreactor (AnDMBR) was operated under a variety of operational conditions, including different sludge retention times (SRTs) of 20 and 40 days in order to determine the effect of SRT on both biological performance and dynamic membrane filtration characteristics. High COD removal efficiencies exceeding 99% were achieved during the operation at both SRTs. Higher filtration resistances were measured during the operation at SRT of 40 days in comparison to SRT of 20 days, applying a stable flux of 2.6 L/m(2) h. The higher filtration resistances coincided with lower extracellular polymeric substances concentration in the bulk sludge at SRT of 40 days, likely resulting in a decreased particle flocculation. Results showed that dynamic membrane technology achieved a stable and high quality permeate and AnDMBRs can be used as a reliable and satisfactory technology for treatment of high strength wastewaters. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dynamic electrical impedance imaging with the interacting multiple model scheme.

PubMed

Kim, Kyung Youn; Kim, Bong Seok; Kim, Min Chan; Kim, Sin; Isaacson, David; Newell, Jonathan C

2005-04-01

In this paper, an effective dynamical EIT imaging scheme is presented for on-line monitoring of the abruptly changing resistivity distribution inside the object, based on the interacting multiple model (IMM) algorithm. The inverse problem is treated as a stochastic nonlinear state estimation problem with the time-varying resistivity (state) being estimated on-line with the aid of the IMM algorithm. In the design of the IMM algorithm multiple models with different process noise covariance are incorporated to reduce the modeling uncertainty. Simulations and phantom experiments are provided to illustrate the proposed algorithm.

Numerical modeling of the transmission dynamics of drug-sensitive and drug-resistant HSV-2

NASA Astrophysics Data System (ADS)

Gumel, A. B.

2001-03-01

A competitive finite-difference method will be constructed and used to solve a modified deterministic model for the spread of herpes simplex virus type-2 (HSV-2) within a given population. The model monitors the transmission dynamics and control of drug-sensitive and drug-resistant HSV-2. Unlike the fourth-order Runge-Kutta method (RK4), which fails when the discretization parameters exceed certain values, the novel numerical method to be developed in this paper gives convergent results for all parameter values.

Characterization of Thin Film Polymers Through Dynamic Mechanical Analysis and Permeation

NASA Technical Reports Server (NTRS)

Herring, Helen

2003-01-01

Thin polymer films are being considered, as candidate materials to augment the permeation resistance of cryogenic hydrogen fuel tanks such as would be required for future reusable launch vehicles. To evaluate performance of candidate films after environmental exposure, an experimental study was performed to measure the thermal/mechanical and permeation performance of six, commercial-grade materials. Dynamic storage modulus, as measured by Dynamic Mechanical Analysis, was found over a range of temperatures. Permeability, as measured by helium gas diffusion, was found at room temperature. Test data was correlated with respect to film type and pre-test exposure to moisture, elevated temperature, and cryogenic temperature. Results indicated that the six films were comparable in performance and their resistance to environmental degradation.

Molecular dynamics simulations reveal the allosteric effect of F1174C resistance mutation to ceritinib in ALK-associated lung cancer.

PubMed

Ni, Zhong; Wang, Xiting; Zhang, Tianchen; Jin, Rong Zhong

2016-12-01

Anaplastic lymphoma kinase (ALK) has become as an important target for the treatment of various human cancers, especially non-small-cell lung cancer. A mutation, F1174C, suited in the C-terminal helix αC of ALK and distal from the small-molecule inhibitor ceritinib bound to the ATP-binding site, causes the emergence of drug resistance to ceritinib. However, the detailed mechanism for the allosteric effect of F1174C resistance mutation to ceritinib remains unclear. Here, molecular dynamics (MD) simulations and binding free energy calculations [Molecular Mechanics/Generalized Born Surface Area (MM/GBSA)] were carried out to explore the advent of drug resistance mutation in ALK. MD simulations observed that the exquisite aromatic-aromatic network formed by residues F1098, F1174, F1245, and F1271 in the wild-type ALK-ceritinib complex was disrupted by the F1174C mutation. The resulting mutation allosterically affected the conformational dynamic of P-loop and caused the upward movement of the P-loop from the ATP-binding site, thereby weakening the interaction between ceritinib and the P-loop. The subsequent MM/GBSA binding free energy calculations and decomposition analysis of binding free energy validated this prediction. This study provides mechanistic insight into the allosteric effect of F1174C resistance mutation to ceritinib in ALK and is expected to contribute to design the next-generation of ALK inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic imaging in electrical impedance tomography of the human chest with online transition matrix identification.

PubMed

Moura, Fernando Silva; Aya, Julio Cesar Ceballos; Fleury, Agenor Toledo; Amato, Marcelo Britto Passos; Lima, Raul Gonzalez

2010-02-01

One of the electrical impedance tomography objectives is to estimate the electrical resistivity distribution in a domain based only on electrical potential measurements at its boundary generated by an imposed electrical current distribution into the boundary. One of the methods used in dynamic estimation is the Kalman filter. In biomedical applications, the random walk model is frequently used as evolution model and, under this conditions, poor tracking ability of the extended Kalman filter (EKF) is achieved. An analytically developed evolution model is not feasible at this moment. The paper investigates the identification of the evolution model in parallel to the EKF and updating the evolution model with certain periodicity. The evolution model transition matrix is identified using the history of the estimated resistivity distribution obtained by a sensitivity matrix based algorithm and a Newton-Raphson algorithm. To numerically identify the linear evolution model, the Ibrahim time-domain method is used. The investigation is performed by numerical simulations of a domain with time-varying resistivity and by experimental data collected from the boundary of a human chest during normal breathing. The obtained dynamic resistivity values lie within the expected values for the tissues of a human chest. The EKF results suggest that the tracking ability is significantly improved with this approach.

Towards a Molecular Understanding of the Link between Imatinib Resistance and Kinase Conformational Dynamics

PubMed Central

Lovera, Silvia; Morando, Maria; Pucheta-Martinez, Encarna; Martinez-Torrecuadrada, Jorge L.; Saladino, Giorgio; Gervasio, Francesco L.

2015-01-01

Due to its inhibition of the Abl kinase domain in the BCR-ABL fusion protein, imatinib is strikingly effective in the initial stage of chronic myeloid leukemia with more than 90% of the patients showing complete remission. However, as in the case of most targeted anti-cancer therapies, the emergence of drug resistance is a serious concern. Several drug-resistant mutations affecting the catalytic domain of Abl and other tyrosine kinases are now known. But, despite their importance and the adverse effect that they have on the prognosis of the cancer patients harboring them, the molecular mechanism of these mutations is still debated. Here by using long molecular dynamics simulations and large-scale free energy calculations complemented by in vitro mutagenesis and microcalorimetry experiments, we model the effect of several widespread drug-resistant mutations of Abl. By comparing the conformational free energy landscape of the mutants with those of the wild-type tyrosine kinases we clarify their mode of action. It involves significant and complex changes in the inactive-to-active dynamics and entropy/enthalpy balance of two functional elements: the activation-loop and the conserved DFG motif. What is more the T315I gatekeeper mutant has a significant impact on the binding mechanism itself and on the binding kinetics. PMID:26606374

Resistance factors for 100% dynamic testing, with and without static load tests : [summary].

DOT National Transportation Integrated Search

2011-01-01

The Federal Highway Administration (FHWA) and : most state departments of transportation have : adopted the Load and Resistance Factor (LRFD) : approach to design. Critical to the design of : piles in this approach is the development of a : resistanc...

Why Finish Your Antibiotics? A Novel, Hands-On, Classroom Approach for Teaching the Dynamics of Antibiotic Resistance

ERIC Educational Resources Information Center

Wassmer, Gary T.; Kipe-Nolt, Judith A.; Chayko, Catherine A.

2006-01-01

We present an effective, engaging, and fun method for teaching how the use or misuse of antibiotics can select for resistant strains of bacteria. This method uses candy as a substitute for strains of bacteria varying in resistance to a given antibiotic. Results and discussion are presented in the context of this emerging healthcare crisis.

The dynamics of rupture in porous media

NASA Astrophysics Data System (ADS)

Stopiński, Wojciech; Ponomaryov, Aleksandr V.; Loś, Vladimir

1991-05-01

This paper presents a laboratory investigation of electric resistivity parameter for samples subject to loading in automatic press of “INOVA” type. The procedure of automatic quasi-continuous measurements of resistivity is briefly outlined. The distribution of mini-electrodes within the sample is described. Also shown is the manner in which reliability can be improved by increasing the repetition of resistivity measurements (every 7 16 s).

Accelerating dynamic genetic conservation efforts: Use of FT-IR spectroscopy for the rapid identification of trees resistant to destructive pathogens

Treesearch

C. Villari; R.A. Sniezko; L.E. Rodriguez-Saona; P. Bonello

2017-01-01

A strong focus on tree germplasm that can resist threats such as non-native insects and pathogens, or a changing climate, is fundamental for successful genetic conservation efforts. However, the unavailability of tools for rapid screening of tree germplasm for resistance to critical pathogens and insect pests is becoming an increasingly serious bottleneck. Here we...

WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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

Grassberger, C; Paganetti, H

Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumedmore » to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation could minimize the probability of resistance, increasing tumor control significantly.« less

Gender Differences in Resistance to Schooling: The Role of Dynamic Peer-Influence and Selection Processes.

PubMed

Geven, Sara; O Jonsson, Jan; van Tubergen, Frank

2017-12-01

Boys engage in notably higher levels of resistance to schooling than girls. While scholars argue that peer processes contribute to this gender gap, this claim has not been tested with longitudinal quantitative data. This study fills this lacuna by examining the role of dynamic peer-selection and influence processes in the gender gap in resistance to schooling (i.e., arguing with teachers, skipping class, not putting effort into school, receiving punishments at school, and coming late to class) with two-wave panel data. We expect that, compared to girls, boys are more exposed and more responsive to peers who exhibit resistant behavior. We estimate hybrid models on 5448 students from 251 school classes in Sweden (14-15 years, 49% boys), and stochastic actor-based models (SIENA) on a subsample of these data (2480 students in 98 classes; 49% boys). We find that boys are more exposed to resistant friends than girls, and that adolescents are influenced by the resistant behavior of friends. These peer processes do not contribute to a widening of the gender gap in resistance to schooling, yet they contribute somewhat to the persistence of the initial gender gap. Boys are not more responsive to the resistant behavior of friends than girls. Instead, girls are influenced more by the resistant behavior of lower status friends than boys. This explains to some extent why boys increase their resistance to schooling more over time. All in all, peer-influence and selection processes seem to play a minor role in gender differences in resistance to schooling. These findings nuance under investigated claims that have been made in the literature.

Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

PubMed Central

Aviran, Sharon; Shah, Priya S.; Schaffer, David V.; Arkin, Adam P.

2010-01-01

Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents. PMID:20711350

COPEWELL: A Conceptual Framework and System Dynamics Model for Predicting Community Functioning and Resilience After Disasters.

PubMed

Links, Jonathan M; Schwartz, Brian S; Lin, Sen; Kanarek, Norma; Mitrani-Reiser, Judith; Sell, Tara Kirk; Watson, Crystal R; Ward, Doug; Slemp, Cathy; Burhans, Robert; Gill, Kimberly; Igusa, Tak; Zhao, Xilei; Aguirre, Benigno; Trainor, Joseph; Nigg, Joanne; Inglesby, Thomas; Carbone, Eric; Kendra, James M

2018-02-01

Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster. We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties. The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature. The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127-137).

Exploiting temporal collateral sensitivity in tumor clonal evolution

PubMed Central

Zhao, Boyang; Sedlak, Joseph C.; Srinivas, Raja; Creixell, Pau; Pritchard, Justin R.; Tidor, Bruce; Lauffenburger, Douglas A.; Hemann, Michael T.

2016-01-01

SUMMARY The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities; a notion that we term ‘temporal collateral sensitivity’. Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1 targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models, and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities. PMID:26924578

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

PubMed

Zhao, Boyang; Sedlak, Joseph C; Srinivas, Raja; Creixell, Pau; Pritchard, Justin R; Tidor, Bruce; Lauffenburger, Douglas A; Hemann, Michael T

2016-03-24

The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities-a notion that we term "temporal collateral sensitivity." Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph(+) acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of two types of neural network for weld quality prediction in small scale resistance spot welding

NASA Astrophysics Data System (ADS)

Wan, Xiaodong; Wang, Yuanxun; Zhao, Dawei; Huang, YongAn

2017-09-01

Our study aims at developing an effective quality monitoring system in small scale resistance spot welding of titanium alloy. The measured electrical signals were interpreted in combination with the nugget development. Features were extracted from the dynamic resistance and electrode voltage curve. A higher welding current generally indicated a lower overall dynamic resistance level. A larger electrode voltage peak and higher change rate of electrode voltage could be detected under a smaller electrode force or higher welding current condition. Variation of the extracted features and weld quality was found more sensitive to the change of welding current than electrode force. Different neural network model were proposed for weld quality prediction. The back propagation neural network was more proper in failure load estimation. The probabilistic neural network model was more appropriate to be applied in quality level classification. A real-time and on-line weld quality monitoring system may be developed by taking advantages of both methods.

A molecular dynamics study of tilt grain boundary resistance to slip and heat transfer in nanocrystalline silicon

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

Chen, Xiang; Chen, Youping; Xiong, Liming

2014-12-28

We present a molecular dynamics study of grain boundary (GB) resistance to dislocation-mediated slip transfer and phonon-mediated heat transfer in nanocrystalline silicon bicrystal. Three most stable 〈110〉 tilt GBs in silicon are investigated. Under mechanical loading, the nucleation and growth of hexagonal-shaped shuffle dislocation loops are reproduced. The resistances of different GBs to slip transfer are quantified through their constitutive responses. Results show that the Σ3 coherent twin boundary (CTB) in silicon exhibits significantly higher resistance to dislocation motion than the Σ9 GB in glide symmetry and the Σ19 GB in mirror symmetry. The distinct GB strengths are explained bymore » the atomistic details of the dislocation-GB interaction. Under thermal loading, based on a thermostat-induced heat pulse model, the resistances of the GBs to transient heat conduction in ballistic-diffusive regime are characterized. In contrast to the trend found in the dislocation-GB interaction in bicrystal models with different GBs, the resistances of the same three GBs to heat transfer are strikingly different. The strongest dislocation barrier Σ3 CTB is almost transparent to heat conduction, while the dislocation-permeable Σ9 and Σ19 GBs exhibit larger resistance to heat transfer. In addition, simulation results suggest that the GB thermal resistance not only depends on the GB energy but also on the detailed atomic structure along the GBs.« less

A comparison of whole-body vibration and resistance training on total work in the rotator cuff.

PubMed

Hand, Jason; Verscheure, Susan; Osternig, Louis

2009-01-01

Whole-body vibration machines are a relatively new technology being implemented in the athletic setting. Numerous authors have examined the proposed physiologic mechanisms of vibration therapy and performance outcomes. Changes have mainly been observed in the lower extremity after individual exercises, with minimal attention to the upper extremity and resistance training programs. To examine the effects of a novel vibration intervention directed at the upper extremity as a precursor to a supervised, multijoint dynamic resistance training program. Randomized controlled trial. National Collegiate Athletic Association Division IA institution. Thirteen female student-athletes were divided into the following 2 treatment groups: (1) whole-body vibration and resistance training or (2) resistance training only. Participants in the vibration and resistance training group used an experimental vibration protocol of 2 x 60 seconds at 4 mm and 50 Hz, in a modified push-up position, 3 times per week for 10 weeks, just before their supervised resistance training session. Isokinetic total work measurements of the rotator cuff were collected at baseline and at week 5 and week 10. No differences were found between the treatment groups (P > .05). However, rotator cuff output across time increased in both groups (P < .05). Although findings did not differ between the groups, the use of whole-body vibration as a precursor to multijoint exercises warrants further investigation because of the current lack of literature on the topic. Our results indicate that indirectly strengthening the rotator cuff using a multijoint dynamic resistance training program is possible.

CRISPR Associated Diversity within a Population of Sulfolobus islandicus

PubMed Central

Held, Nicole L.; Herrera, Alfa; Cadillo-Quiroz, Hinsby; Whitaker, Rachel J.

2010-01-01

Background Predator-prey models for virus-host interactions predict that viruses will cause oscillations of microbial host densities due to an arms race between resistance and virulence. A new form of microbial resistance, CRISPRs (clustered regularly interspaced short palindromic repeats) are a rapidly evolving, sequence-specific immunity mechanism in which a short piece of invading viral DNA is inserted into the host's chromosome, thereby rendering the host resistant to further infection. Few studies have linked this form of resistance to population dynamics in natural microbial populations. Methodology/Principal Findings We examined sequence diversity in 39 strains of the archeaon Sulfolobus islandicus from a single, isolated hot spring from Kamchatka, Russia to determine the effects of CRISPR immunity on microbial population dynamics. First, multiple housekeeping genetic markers identify a large clonal group of identical genotypes coexisting with a diverse set of rare genotypes. Second, the sequence-specific CRISPR spacer arrays split the large group of isolates into two very different groups and reveal extensive diversity and no evidence for dominance of a single clone within the population. Conclusions/Significance The evenness of resistance genotypes found within this population of S. islandicus is indicative of a lack of strain dominance, in contrast to the prediction for a resistant strain in a simple predator-prey interaction. Based on evidence for the independent acquisition of resistant sequences, we hypothesize that CRISPR mediated clonal interference between resistant strains promotes and maintains diversity in this natural population. PMID:20927396

Nonlinear Dynamics of a Spring-Supported Piston in a Vibrated Liquid-Filled Housing: II. Experiments

NASA Astrophysics Data System (ADS)

O'Hern, T. J.; Torczynski, J. R.; Clausen, J. R.

2016-11-01

The nonlinear dynamics of a piston supported by a spring in a vibrated liquid-filled housing is investigated experimentally. The housing containing the piston and the liquid is subjected to vibrations along its axis. A post fixed to the housing penetrates a hole through the piston and produces a flow resistance that depends on piston position. Flexible bellows attached to the housing ends enable the piston, liquid, and bellows to execute a collective motion that forces little liquid through the flow resistance. The low damping of this motion leads to a resonance, at which the flow-resistance nonlinearity produces a net force on the piston that can cause it to compress its spring. Experiments are performed to investigate the nonlinear dynamics of this system, and these results are compared to theoretical and numerical results. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Quantifying the behavior of price dynamics at opening time in stock market

NASA Astrophysics Data System (ADS)

Ochiai, Tomoshiro; Takada, Hideyuki; Nacher, Jose C.

2014-11-01

The availability of huge volume of financial data has offered the possibility for understanding the markets as a complex system characterized by several stylized facts. Here we first show that the time evolution of the Japan’s Nikkei stock average index (Nikkei 225) futures follows the resistance and breaking-acceleration effects when the complete time series data is analyzed. However, in stock markets there are periods where no regular trades occur between the close of the market on one day and the next day’s open. To examine these time gaps we decompose the time series data into opening time and intermediate time. Our analysis indicates that for the intermediate time, both the resistance and the breaking-acceleration effects are still observed. However, for the opening time there are almost no resistance and breaking-acceleration effects, and volatility is always constantly high. These findings highlight unique dynamic differences between stock markets and forex market and suggest that current risk management strategies may need to be revised to address the absence of these dynamic effects at the opening time.

Effects of graphene oxide on the performance, microbial community dynamics and antibiotic resistance genes reduction during anaerobic digestion of swine manure.

PubMed

Zhang, Junya; Wang, Ziyue; Wang, Yawei; Zhong, Hui; Sui, Qianwen; Zhang, Changping; Wei, Yuansong

2017-12-01

The role of graphene oxide (GO) on anaerobic digestion (AD) of swine manure concerning the performance, microbial community and antibiotic resistance genes (ARGs) reduction was investigated. Results showed that methane production was reduced by 13.1%, 10.6%, 2.7% and 17.1% at GO concentration of 5mg/L, 50mg/L, 100mg/L and 500mg/L, respectively, but propionate degradation was enhanced along with GO addition. Both bacterial and archaeal community changed little after GO addition. AD could well reduce ARGs abundance, but it was deteriorated at the GO concentration of 50mg/L and 100mg/L and enhanced at 500mg/L, while no obvious changes at 5mg/L. Network and SEM analysis indicated that changes of each ARG was closely associated with variation of microbial community composition, environmental variables contributed most to the dynamics of ARGs indirectly, GO influenced the ARGs dynamics negatively and (heavy metal resistance genes (MRGs)) influenced the most directly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mathematical Modeling and Nonlinear Dynamical Analysis of Cell Growth in Response to Antibiotics

NASA Astrophysics Data System (ADS)

Jin, Suoqin; Niu, Lili; Wang, Gang; Zou, Xiufen

2015-06-01

This study is devoted to the revelation of the dynamical mechanisms of cell growth in response to antibiotics. We establish a mathematical model of ordinary differential equations for an antibiotic-resistant growth system with one positive feedback loop. We perform a dynamical analysis of the behavior of this model system. We present adequate sets of conditions that can guarantee the existence and stability of biologically-reasonable steady states. Using bifurcation analysis and numerical simulation, we show that the relative growth rate, which is defined as the ratio of the cell growth rate to the basal cell growth rate in the absence of antibiotics, can exhibit bistable behavior in an extensive range of parameters that correspond to a growth state and a nongrowth state in biology. We discover that both antibiotic and antibiotic resistance genes can cooperatively enhance bistability, whereas the cooperative coefficient of feedback can contribute to the onset of bistability. These results would contribute to a better understanding of not only the evolution of antibiotics but also the emergence of drug resistance in other diseases.

Effects of Ohmic Resistance on Dynamic Characteristics and Impedance of Micro/Nano Cantilever Beam resonators

NASA Astrophysics Data System (ADS)

Rezazadeh, Ghader; Keyvani, Aliasghar; Sadeghi, Morteza H.; Bahrami, Manouchehr

2013-06-01

Effects of Ohmic resistance on MEMS/NEMS vibrating structures that have always been dismissed in some situations may cause important changes in resonance properties and impedance parameters of the MEMS/NEMS based circuits. In this paper it is aimed to present a theoretical model to precisely investigate the problem on a simple cantilever-substrate resonator. In this favor the Ohm's current law and charge conservation law have been merged to find a differential Equation for voltage propagation on the beam and because mostly nano structures are expected as the scope of the problem, modified couple stress theory is used to formulate the dynamic motion of the beam. The two governing equations were coupled and both nonlinear that have been solved simultaneously using a Galerkin based state space formulation. The obtained results that are in exact agreement with previous works show that dynamic pull-in voltage, switching time, and impedance of structure as a MEMS capacitor especially in frequencies higher than natural resonance frequency strongly relay on electrical resistance of the beam and substrate material.

Enhanced energy coupling and x-ray emission in Z-pinch plasma implosions

NASA Astrophysics Data System (ADS)

Whitney, K. G.; Thornhill, J. W.; Apruzese, J. P.; Davis, J.; Deeney, C.; Coverdale, C. A.

2004-08-01

Recent experiments conducted on the Saturn pulsed-power generator at Sandia National Laboratories [R. B. Spielman et al., in Proceedings of the Second International Conference on Dense Z Pinches, Laguna Beach, CA, 1989, edited by N. R. Pereira, J. Davis, and N. Rostoker (American Institute of Physics, New York, 1989), p. 3] have produced large amounts of x-ray output, which cannot be accounted for in conventional magnetohydrodynamic (MHD) calculations. In these experiments, the Saturn current had a rise time of ~180 ns in contrast to a rise time of ~60 ns in Saturn's earlier mode of operation. In both aluminum and tungsten wire-array Z-pinch implosions, 2-4 times more x-ray output was generated than could be supplied according to one-dimensional (1D) magnetohydrodynamic calculations by the combined action of the j×B acceleration forces and ohmic heating (as described by a classical Braginskii resistivity). In this paper, we reexamine the problem of coupling transmission line circuits to plasma fluid equations and derive expressions for the Z-pinch load circuit resistance and inductance that relate these quantities in a 1D analysis to the surface resistivity of the fluid, and to the magnetic field energy that is stored in the vacuum diode, respectively. Enhanced energy coupling in this analysis, therefore, comes from enhancements to the surface resistivity, and we show that plasma resistivities approximately three orders of magnitude larger than classical are needed in order to achieve energy inputs that are comparable to the Saturn experiment x-ray outputs. Large enhancements of the plasma resistivity increase the rate of magnetic field and current diffusion, significantly modify the qualitative features of the MHD, and raise important questions as to how the plasma fluid dynamics converts enhanced energy inputs into enhanced x-ray outputs. One-dimensional MHD calculations in which resistivity values are adjusted phenomenologically are used to illustrate how various dynamical assumptions influence the way enhanced energy inputs are channeled by the fluid dynamics. Variations in the parameters of the phenomenological model are made in order to determine how sensitively they influence the dynamics and the degree to which the calculated x-ray outputs can be made to replicate the kinds of large variations in the experimental x-ray power data that were observed in three nominally identical aluminum wire shots on Saturn.

Using In Vitro Dynamic Models To Evaluate Fluoroquinolone Activity against Emergence of Resistant Salmonella enterica Serovar Typhimurium

PubMed Central

Lee, Seung-Jin; Awji, Elias Gebru; Park, Na-hye

2016-01-01

ABSTRACT The objectives of this study were to determine pharmacokinetic/pharmacodynamic (PK/PD) indices of fluoroquinolones that minimize the emergence of resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) using in vitro dynamic models and to establish mechanisms of resistance. Three fluoroquinolones, difloxacin (DIF), enrofloxacin (ENR), and marbofloxacin (MAR), at five dose levels and 3 days of treatment were simulated. Bacterial killing-regrowth kinetics and emergence of resistant bacteria after antibacterial drug exposure were quantified. PK/PD indices associated with different levels of antibacterial activity were computed. Mechanisms of fluoroquinolone resistance were determined by analyzing target mutations in the quinolone resistance-determining regions (QRDRs) and by analyzing overexpression of efflux pumps. Maximum losses in susceptibility of fluoroquinolone-exposed S. Typhimurium occurred at a simulated AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 47 to 71. Target mutations in gyrA (S83F) and overexpression of acrAB-tolC contributed to decreased susceptibility in fluoroquinolone-exposed S. Typhimurium. The current data suggest AUC/MIC (AUC/mutant prevention concentration [MPC])-dependent selection of resistant mutants of S. Typhimurium, with AUC/MPC ratios of 69 (DIF), 62 (ENR), and 39 (MAR) being protective against selection of resistant mutants. These values could not be achieved in veterinary clinical areas under the current recommended therapeutic doses of the fluoroquinolones, suggesting the need to reassess the current dosing regimen to include both clinical efficacy and minimization of emergence of resistant bacteria. PMID:27895011

The Versatile Mutational Resistome of Pseudomonas aeruginosa

PubMed Central

López-Causapé, Carla; Cabot, Gabriel; del Barrio-Tofiño, Ester; Oliver, Antonio

2018-01-01

One of the most striking features of Pseudomonas aeruginosa is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from in vitro assays on the evolution of antibiotic resistance, in vivo monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of P. aeruginosa antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the P. aeruginosa mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms. PMID:29681898

The Versatile Mutational Resistome of Pseudomonas aeruginosa.

PubMed

López-Causapé, Carla; Cabot, Gabriel; Del Barrio-Tofiño, Ester; Oliver, Antonio

2018-01-01

One of the most striking features of Pseudomonas aeruginosa is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from in vitro assays on the evolution of antibiotic resistance, in vivo monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of P. aeruginosa antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the P. aeruginosa mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms.

Dynamic evolution of resistance gene analogs in the orthologous genomic regions of powdery mildew resistance gene MlIW170 in Triticum dicoccoides and Aegilops tauschii

USDA-ARS?s Scientific Manuscript database

Wheat is one of the most important staple grain crops in the world. Powdery mildew disease caused by Blumeria graminis f.sp. tritici can result in significant losses in both grain yield and quality in wheat. In this study, the wheat powdery mildew resistance gene MlIW170 locus located on the short ...

Scaling up from greenhouse resistance to fitness in the field for a host of an emerging forest disease

PubMed Central

Hayden, Katherine J; Garbelotto, Matteo; Dodd, Richard; Wright, Jessica W

2013-01-01

Forest systems are increasingly threatened by emergent, exotic diseases, yet management strategies for forest trees may be hindered by long generation times and scant background knowledge. We tested whether nursery disease resistance and growth traits have predictive value for the conservation of Notholithocarpus densiflorus, the host most susceptible to sudden oak death. We established three experimental populations to assess nursery growth and resistance to Phytophthora ramorum, and correlations between nursery-derived breeding values with seedling survival in a field disease trial. Estimates of nursery traits’ heritability were low to moderate, with lowest estimates for resistance traits. Within the field trial, survival likelihood was increased in larger seedlings and decreased with the development of disease symptoms. The seed-parent family wide likelihood of survival was likewise correlated with family predictors for size and resistance to disease in 2nd year laboratory assays, though not resistance in 1st year leaf assays. We identified traits and seedling families with increased survivorship in planted tanoaks, and a framework to further identify seed parents favored for restoration. The additive genetic variation and seedling disease dynamics we describe hold promise to refine current disease models and expand the understanding of evolutionary dynamics of emergent infectious diseases in highly susceptible hosts. PMID:24062805

Is Earth F**ked? Dynamical Futility of Global Environmental Management and Possibilities for Sustainability via Direct Action Activism

NASA Astrophysics Data System (ADS)

wErnEr, B.

2012-12-01

Environmental challenges are dynamically generated within the dominant global culture principally by the mismatch between short-time-scale market and political forces driving resource extraction/use and longer-time-scale accommodations of the Earth system to these changes. Increasing resource demand is leading to the development of two-way, nonlinear interactions between human societies and environmental systems that are becoming global in extent, either through globalized markets and other institutions or through coupling to global environmental systems such as climate. These trends are further intensified by dissipation-reducing technological advances in transactions, communication and transport, which suppress emergence of longer-time-scale economic and political levels of description and facilitate long-distance connections, and by predictive environmental modeling, which strengthens human connections to a short-time-scale virtual Earth, and weakens connections to the longer time scales of the actual Earth. Environmental management seeks to steer fast scale economic and political interests of a coupled human-environmental system towards longer-time-scale consideration of benefits and costs by operating within the confines of the dominant culture using a linear, engineering-type connection to the system. Perhaps as evidenced by widespread inability to meaningfully address such global environmental challenges as climate change and soil degradation, nonlinear connections reduce the ability of managers to operate outside coupled human-environmental systems, decreasing their effectiveness in steering towards sustainable interactions and resulting in managers slaved to short-to-intermediate-term interests. In sum, the dynamics of the global coupled human-environmental system within the dominant culture precludes management for stable, sustainable pathways and promotes instability. Environmental direct action, resistance taken from outside the dominant culture, as in protests, blockades and sabotage by indigenous peoples, workers, anarchists and other activist groups, increases dissipation within the coupled system over fast to intermediate scales and pushes for changes in the dominant culture that favor transition to a stable, sustainable attractor. These dynamical relationships are illustrated and explored using a numerical model that simulates the short-, intermediate- and long-time-scale dynamics of the coupled human-environmental system. At fast scales, economic and political interests exploit environmental resources through a maze of environmental management and resistance, guided by virtual Earth predictions. At intermediate scales, managers become slaved to economic and political interests, which adapt to and repress resistance, and resistance is guided by patterns of environmental destruction. At slow scales, resistance interacts with the cultural context, which co-evolves with the environment. The transition from unstable dynamics to sustainability is sensitively dependent on the level of participation in and repression of resistance. Because of their differing impact inside and outside the dominant culture, virtual Earth predictions can either promote or oppose sustainability. Supported by the National Science Foundation, Geomorphology and Land Use Dynamics Program.

RADIATION-RESISTANT FIBER OPTIC STRAIN SENSORS FOR SNS TARGET INSTRUMENTATION

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

Blokland, Willem; Bryan, Jeff; Riemer, Bernie

2016-01-01

Measurement of stresses and strains in the mercury tar-get vessel of the Spallation Neutron Source (SNS) is important to understand the structural dynamics of the target. This work reports the development of radiation-resistant fiber optic strain sensors for the SNS target in-strumentation.

Data driven weed management: Tracking herbicide resistance at the landscape scale

USDA-ARS?s Scientific Manuscript database

Limiting the prevalence of herbicide resistant (HR) weeds requires consistent management implementation across space and time. Although weed population dynamics operate at scales above farm-level, the emergent effect of neighboring management decisions on in-field weed densities and the spread of re...

Significance testing of clinical data using virus dynamics models with a Markov chain Monte Carlo method: application to emergence of lamivudine-resistant hepatitis B virus.

PubMed Central

Burroughs, N J; Pillay, D; Mutimer, D

1999-01-01

Bayesian analysis using a virus dynamics model is demonstrated to facilitate hypothesis testing of patterns in clinical time-series. Our Markov chain Monte Carlo implementation demonstrates that the viraemia time-series observed in two sets of hepatitis B patients on antiviral (lamivudine) therapy, chronic carriers and liver transplant patients, are significantly different, overcoming clinical trial design differences that question the validity of non-parametric tests. We show that lamivudine-resistant mutants grow faster in transplant patients than in chronic carriers, which probably explains the differences in emergence times and failure rates between these two sets of patients. Incorporation of dynamic models into Bayesian parameter analysis is of general applicability in medical statistics. PMID:10643081

Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/Gαs/AC/cAMP/PKA signaling cascade.

PubMed

Li, Ting; Liu, Nannan

2017-12-01

This study explores the role of G-protein-coupled receptor-intracellular signaling in the development of P450-mediated insecticide resistance in mosquitoes, Culex quinquefasciatus , focusing on the essential function of the GPCRs and their downstream effectors of Gs alpha subunit protein (Gαs) and adenylyl cyclase (ACs) in P450-mediated insecticide resistance of Culex mosquitoes. Our RNAi-mediated functional study showed that knockdown of Gαs caused the decreased expression of the downstream effectors of ACs and PKAs in the GPCR signaling pathway and resistance P450 genes, whereas knockdown of ACs decreased the expression of PKAs and resistance P450 genes. Knockdown of either Gαs or ACs resulted in an increased susceptibility of mosquitoes to permethrin. These results add significantly to our understanding of the molecular basis of resistance P450 gene regulation through GPCR/Gαs/AC/cAMP-PKA signaling pathways in the insecticide resistance of mosquitoes. The temporal and spatial dynamic analyses of GPCRs, Gαs, ACs, PKAs, and P450s in two insecticide resistant mosquito strains revealed that all the GPCR signaling pathway components tested, namely GPCRs, Gαs, ACs and PKAs, were most highly expressed in the brain for both resistant strains, suggesting the role played by these genes in signaling transduction and regulation. The resistance P450 genes were mainly expressed in the brain, midgut and malpighian tubules (MTs), suggesting their critical function in the central nervous system and importance for detoxification. The temporal dynamics analysis for the gene expression showed a diverse expression profile during mosquito development, indicating their initially functional importance in response to exposure to insecticides during their life stages.

[Neisseria gonorrhoeae: antimicrobial resistance and study of population dynamics. Situation in Barcelona in 2011].

PubMed

Serra-Pladevall, Judit; Barberá-Gracia, María Jesús; Roig-Carbajosa, Glòria; Juvé-Saumell, Rosa; Gonzalez-Lopez, Juan José; Bartolomé-Comas, Rosa; Andreu-Domingo, Antònia

2013-11-01

Due to the high rates of antimicrobial resistance to certain antibiotics, together with the emergence of Neisseria gonorrhoeae (NG) with reduced susceptibility and resistance to third-generation cephalosporins, gonococcal infection is becoming a public health problem. The objectives of the study were: To keep track of the antimicrobial susceptibility of NG strains obtained from January to August 2011. To study the population dynamics. The antimicrobial susceptibility was studied by disk-diffusion and E-test. The genotyping was performed by NG-MAST method. Of a total of 100strains studied, 59% showed intermediate sensitivity to penicillin and 9% were resistant. According to EUCAST, we detected 3gonococci with reduced susceptibility to ceftriaxone, 10 to cefixime and one with high-level resistance to both antibiotics (MIC 1.5μg/ml). MIC50 and MIC90 to cefixime were 0.016 and 0.125μg/ml, respectively, whereas to ceftriaxone they were <0.016 and 0.064μg/ml, respectively. Almost all (99%) of the strains were resistant to doxycycline, 53% to ciprofloxacin, 3% to azithromycin, and 1% to spectinomycin. The most prevalent ST was ST1407, predominantly associated to resistance or reduced sensitivity to cephalosporins or macrolides. NG has developed significant rates of resistance to various antibiotics. One strain has been detected with high level resistance to third generation cephalosporins, and several strains with reduced susceptibility. An increase in MIC50 and MIC90 to these antibiotics has also been observed. NG population structure remains stable and common to the rest of Europe, although two new ST (ST7226 and ST7227) have been identified that could be selected and acquire high levels of resistance to cephalosporins. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Interplay Between Antibiotic Resistance and Virulence During Disease Promoted by Multidrug-Resistant Bacteria

PubMed Central

Geisinger, Edward

2017-01-01

Abstract Diseases caused by antibiotic-resistant bacteria in hospitals are the outcome of complex relationships between several dynamic factors, including bacterial pathogenicity, the fitness costs of resistance in the human host, and selective forces resulting from interventions such as antibiotic therapy. The emergence and fate of mutations that drive antibiotic resistance are governed by these interactions. In this review, we will examine how different forms of antibiotic resistance modulate bacterial fitness and virulence potential, thus influencing the ability of pathogens to evolve in the context of nosocomial infections. We will focus on 3 important multidrug-resistant pathogens that are notoriously problematic in hospitals: Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. An understanding of how antibiotic resistance mutations shape the pathobiology of multidrug-resistant infections has the potential to drive novel strategies that can control the development and spread of drug resistance. PMID:28375515

Study on the thermal resistance in secondary particles chain of silica aerogel by molecular dynamics simulation

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

Liu, M.; Department of Physics, University of Chinese Academy of Sciences, Beijing 100049; Qiu, L., E-mail: qiulin111@sina.com, E-mail: jzzhengxinghua@163.com

2014-09-07

In this article, molecular dynamics simulation was performed to study the heat transport in secondary particles chain of silica aerogel. The two adjacent particles as the basic heat transport unit were modelled to characterize the heat transfer through the calculation of thermal resistance and vibrational density of states (VDOS). The total thermal resistance of two contact particles was predicted by non-equilibrium molecular dynamics simulations (NEMD). The defects were formed by deleting atoms in the system randomly first and performing heating and quenching process afterwards to achieve the DLCA (diffusive limited cluster-cluster aggregation) process. This kind of treatment showed a verymore » reasonable prediction of thermal conductivity for the silica aerogels compared with the experimental values. The heat transport was great suppressed as the contact length increased or defect concentration increased. The constrain effect of heat transport was much significant when contact length fraction was in the small range (<0.5) or the defect concentration is in the high range (>0.5). Also, as the contact length increased, the role of joint thermal resistance played in the constraint of heat transport was increasing. However, the defect concentration did not affect the share of joint thermal resistance as the contact length did. VDOS of the system was calculated by numerical method to characterize the heat transport from atomic vibration view. The smaller contact length and greater defect concentration primarily affected the longitudinal acoustic modes, which ultimately influenced the heat transport between the adjacent particles.« less

Impaired sympathetic vascular regulation in humans after acute dynamic exercise

NASA Technical Reports Server (NTRS)

Halliwill, J. R.; Taylor, J. A.; Eckberg, D. L.

1996-01-01

1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena.

Elevated temperature mechanical behavior of monolithic and SiC whisker-reinforced silicon nitrides

NASA Technical Reports Server (NTRS)

Salem, Jonathan A.; Choi, Sung R.; Sanders, William A.; Fox, Dennis S.

1991-01-01

The mechanical behavior of a 30 volume percent SiC whisker reinforced silicon nitride and a similar monolithic silicon nitride were measured at several temperatures. Measurements included strength, fracture toughness, crack growth resistance, dynamic fatigue susceptibility, post oxidation strength, and creep rate. Strength controlling defects were determined with fractographic analysis. The addition of SiC whiskers to silicon nitride did not substantially improve the strength, fracture toughness, or crack growth resistance. However, the fatigue resistance, post oxidation strength, and creep resistance were diminished by the whisker addition.

The Major Mobilization of the Unconscious and the Total Removal of Resistance in Davanloo's Intensive Short-term Dynamic Psychotherapy Part I: An Introduction.

PubMed

Hickey, Catherine

2015-01-01

Davanloo's Intensive Short-term Dynamic Psychotherapy has been the subject of various reviews. Davanloo has published extensively on his early work, but there have been no publications on his most recent work-most notably his Montreal Closed-circuit training program. This program focuses on his most recent discoveries and techniques and is a unique, videotaped supervisory program. It focuses on self-assessment and peer-assessment. It is also a unique format in which to review Davanloo's theoretical conceptions of resistance and the transference component of the resistance. This paper will review the early work of Davanloo as well as his most recent research findings. A case from the Montreal Closed-circuit training program will be reviewed in detail to highlight these findings.

Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops.

PubMed

Lang, Walter H; Coats, Julie E; Majka, Jerzy; Hura, Greg L; Lin, Yuyen; Rasnik, Ivan; McMurray, Cynthia T

2011-10-18

Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation.

Determination of Heritage SSME Pogo Suppressor Resistance and Inertance from Waterflow Pulse Testing

NASA Technical Reports Server (NTRS)

McDougal, Chris; Eberhart, Chad; Lee, Erik

2016-01-01

Waterflow tests of a heritage Space Shuttle Main Engine pogo suppressor were performed to experimentally quantify the resistance and inertance provided by the suppressor. Measurements of dynamic pressure and flow rate in response to pulsing flow were made throughout the test loop. A unique system identification methodology combined all sensor measurements with a one-dimensional perturbational flow model of the complete water flow loop to spatially translate physical measurements to the device under test. Multiple techniques were then employed to extract the effective resistance and inertance for the pogo suppressor. Parameters such as steady flow rate, perturbational flow rate magnitude, and pulse frequency were investigated to assess their influence on the behavior of the pogo suppressor dynamic response. These results support validation of the RS-25 pogo suppressor performance for use on the Space Launch System Core Stage.

High-velocity deformation of Al0.3CoCrFeNi high-entropy alloy: Remarkable resistance to shear failure

PubMed Central

Li, Z.; Zhao, S.; Diao, H.; Liaw, P. K.; Meyers, M. A.

2017-01-01

The mechanical behavior of a single phase (fcc) Al0.3CoCrFeNi high-entropy alloy (HEA) was studied in the low and high strain-rate regimes. The combination of multiple strengthening mechanisms such as solid solution hardening, forest dislocation hardening, as well as mechanical twinning leads to a high work hardening rate, which is significantly larger than that for Al and is retained in the dynamic regime. The resistance to shear localization was studied by dynamically-loading hat-shaped specimens to induce forced shear localization. However, no adiabatic shear band could be observed. It is therefore proposed that the excellent strain hardening ability gives rise to remarkable resistance to shear localization, which makes this material an excellent candidate for penetration protection applications such as armors. PMID:28210000

Nontoxic colloidal particles impede antibiotic resistance of swarming bacteria by disrupting collective motion and speed

NASA Astrophysics Data System (ADS)

Lu, Shengtao; Liu, Fang; Xing, Bengang; Yeow, Edwin K. L.

2015-12-01

A monolayer of swarming B. subtilis on semisolid agar is shown to display enhanced resistance against antibacterial drugs due to their collective behavior and motility. The dynamics of swarming motion, visualized in real time using time-lapse microscopy, prevents the bacteria from prolonged exposure to lethal drug concentrations. The elevated drug resistance is significantly reduced when the collective motion of bacteria is judiciously disrupted using nontoxic polystyrene colloidal particles immobilized on the agar surface. The colloidal particles block and hinder the motion of the cells, and force large swarming rafts to break up into smaller packs in order to maneuver across narrow spaces between densely packed particles. In this manner, cohesive rafts rapidly lose their collectivity, speed, and group dynamics, and the cells become vulnerable to the drugs. The antibiotic resistance capability of swarming B. subtilis is experimentally observed to be negatively correlated with the number density of colloidal particles on the engineered surface. This relationship is further tested using an improved self-propelled particle model that takes into account interparticle alignment and hard-core repulsion. This work has pertinent implications on the design of optimal methods to treat drug resistant bacteria commonly found in swarming colonies.

Modeling the full length HIV-1 Gag polyprotein reveals the role of its p6 subunit in viral maturation and the effect of non-cleavage site mutations in protease drug resistance.

PubMed

Su, Chinh Tran-To; Kwoh, Chee-Keong; Verma, Chandra Shekhar; Gan, Samuel Ken-En

2017-12-27

HIV polyprotein Gag is increasingly found to contribute to protease inhibitor resistance. Despite its role in viral maturation and in developing drug resistance, there remain gaps in the knowledge of the role of certain Gag subunits (e.g. p6), and that of non-cleavage mutations in drug resistance. As p6 is flexible, it poses a problem for structural experiments, and is hence often omitted in experimental Gag structural studies. Nonetheless, as p6 is an indispensable component for viral assembly and maturation, we have modeled the full length Gag structure based on several experimentally determined constraints and studied its structural dynamics. Our findings suggest that p6 can mechanistically modulate Gag conformations. In addition, the full length Gag model reveals that allosteric communication between the non-cleavage site mutations and the first Gag cleavage site could possibly result in protease drug resistance, particularly in the absence of mutations in Gag cleavage sites. Our study provides a mechanistic understanding to the structural dynamics of HIV-1 Gag, and also proposes p6 as a possible drug target in anti-HIV therapy.

Measurement of resistance switching dynamics in copper sulfide memristor structures

NASA Astrophysics Data System (ADS)

McCreery, Kaitlin; Olson, Matthew; Teitsworth, Stephen

Resistance switching materials are the subject of current research in large part for their potential to enable novel computing devices and architectures such as resistance random access memories and neuromorphic chips. A common feature of memristive structures is the hysteretic switching between high and low resistance states which is induced by the application of a sufficiently large electric field. Here, we describe a relatively simple wet chemistry process to fabricate Cu2 S / Cu memristive structures with Cu2 S film thickness ranging up to 150 micron. In this case, resistance switching is believed to be mediated by electromigration of Cu ions from the Cu substrate into the Cu2 S film. Hysteretic current-voltage curves are measured and reveal switching voltages of about 0.8 Volts with a relatively large variance and independent of film thickness. In order to gain insight into the dynamics and variability of the switching process, we have measured the time-dependent current response to voltage pulses of varying height and duration with a time resolution of 1 ns. The transient response consists of a deterministic RC component as well as stochastically varying abrupt current steps that occur within a few microseconds of the pulse application.

Simulations of CYP51A from Aspergillus fumigatus in a model bilayer provide insights into triazole drug resistance

PubMed Central

Nash, Anthony; Rhodes, Johanna

2018-01-01

Abstract Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B. The derived structures, wild type, and L98H mutant are positioned within a lipid membrane bilayer and subjected to molecular dynamics simulations in order improve the accuracy of both models. The structural analysis from our simulations suggests a decrease in active site surface from the formation of hydrogen bonds between the histidine substitution and neighboring polar side chains, potentially preventing the binding of azole drugs. This study yields a biologically relevant structure and set of dynamics of the A. fumigatus Lanosterol 14 alpha-demethylase enzyme and provides further insight into azole antifungal drug resistance. PMID:28992260

Flow resistance interactions on hillslopes with heterogeneous attributes: Effects on runoff hydrograph characteristics

USDA-ARS?s Scientific Manuscript database

An improved modeling framework for capturing the effects of dynamic resistance to overland flow is developed for intensively managed landscapes. The framework builds on the WEPP model but it removes the limitations of the “equivalent” plane and static roughness assumption. The enhanced model therefo...

Understanding and Reducing Faculty Reluctance to Improve Teaching

ERIC Educational Resources Information Center

McCrickerd, Jennifer

2012-01-01

Many believe college instructors resist new teaching practices. In this article, the author develops a hypothesis to understand resistant faculty members, focusing on their likely educational experiences and on insights from psychology. Using Dweck's conception of self-theories and Fischer's conception of dynamic skill-theory, she defends the…

Intestinal Escherichia coli colonization in a mallard duck population over four consecutive winter seasons.

PubMed

Rödiger, Stefan; Kramer, Toni; Frömmel, Ulrike; Weinreich, Jörg; Roggenbuck, Dirk; Guenther, Sebastian; Schaufler, Katharina; Schröder, Christian; Schierack, Peter

2015-09-01

We report the population structure and dynamics of one Escherichia coli population of wild mallard ducks in their natural environment over four winter seasons, following the characterization of 100 isolates each consecutive season. Macro-restriction analysis was used to define isolates variously as multi- or 1-year pulsed-field gel electrophoresis (PFGE) types. Isolates were characterized genotypically based on virulence-associated genes (VAGs), phylogenetic markers, and phenotypically based on haemolytic activity, antimicrobial resistance, adhesion to epithelial cells, microcin production, motility and carbohydrate metabolism. Only 12 out of 220 PFGE types were detectable over more than one winter, and classified as multi-year PFGE types. There was a dramatic change of PFGE types within two winter seasons. Nevertheless, the genetic pool (VAGs) and antimicrobial resistance pattern remained remarkably stable. The high diversity and dynamics of this E. coli population were also demonstrated by the occurrence of PFGE subtypes and differences between isolates of one PFGE type (based on VAGs, antimicrobial resistance and adhesion rates). Multi- and 1-year PFGE types differed in antimicrobial resistance, VAGs and adhesion. Other parameters were not prominent colonization factors. In conclusion, the high diversity, dynamics and stable genetic pool of an E. coli population seem to enable their successful colonization of host animal population over time. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Control of base-excited dynamical systems through piezoelectric energy harvesting absorber

NASA Astrophysics Data System (ADS)

Abdelmoula, H.; Dai, H. L.; Abdelkefi, A.; Wang, L.

2017-09-01

The spring-mass absorber usually offers a good control to dynamical systems under direct base excitations for a specific value of the excitation frequency. As the vibrational energy of a primary dynamical system is transferred to the absorber, it gets dissipated. In this study, this energy is no longer dissipated but converted to available electrical power by designing efficient energy harvesters. A novel design of a piezoelectric beam installed inside an elastically-mounted dynamical system undergoing base excitations is considered. A design is carried out in order to determine the properties and dimensions of the energy harvester with the constraint of simultaneously decreasing the oscillating amplitudes of the primary dynamical system and increasing the harvested power of the energy harvesting absorber. An analytical model for the coupled system is constructed using Euler-Lagrange principle and Galerkin discretization. Different strategies for controlling the primary structure displacement and enhancing the harvested power as functions of the electrical load resistance and thickness of the beam substrate are performed. The linear polynomial approximation of the system’s key parameters as a function of the beam’s substrate thickness is first carried out. Then, the gradient method is applied to determine the adequate values of the electrical load resistance and thickness of the substrate under the constraints of minimizing the amplitudes of the primary structure or maximizing the levels of the harvested power. After that, an iterative strategy is considered in order to simultaneously minimize the amplitudes of the primary structure and maximize the levels of the harvested power as functions of the thickness of the substrate and electrical load resistance. In addition to harmonic excitations, the coupled system subjected to a white noise is explored. Through this analysis, the load resistance and thickness of the substrate of the piezoelectric energy harvester are determined. It is shown that, in addition to efficiently control the oscillating amplitudes of the primary structure, broadband resonance regions can take place and hence high levels of the harvested power are obtained.

Do steady fast magnetic dynamos exist?

NASA Technical Reports Server (NTRS)

Finn, John M.; Ott, Edward; Hanson, James D.; Kan, Ittai

1989-01-01

This paper considers the question of the existense of a steady fast kinematic magnetic dynamo for a conducting fluid with a steady velocity field and vanishingly small electrical resistivity. The analysis of examples of steady dynamos, found by considering the zero-resistivity dynamics, indicated that, for sufficiently small resistivity, dynamo action can indeed occur in steady smooth three-dimensional chaotic fluid flows and that fast dynamos should consequently be a typical occurrence for such flows.

Deciphering the evolution of herbicide resistance in weeds.

PubMed

Délye, Christophe; Jasieniuk, Marie; Le Corre, Valérie

2013-11-01

Resistance to herbicides in arable weeds is increasing rapidly worldwide and threatening global food security. Resistance has now been reported to all major herbicide modes of action despite the development of resistance management strategies in the 1990s. We review here recent advances in understanding the genetic bases and evolutionary drivers of herbicide resistance that highlight the complex nature of selection for this adaptive trait. Whereas early studied cases of resistance were highly herbicide-specific and largely under monogenic control, cases of greatest concern today generally involve resistance to multiple modes of action, are under polygenic control, and are derived from pre-existing stress response pathways. Although 'omics' approaches should enable unraveling the genetic bases of complex resistances, the appearance, selection, and spread of herbicide resistance in weed populations can only be fully elucidated by focusing on evolutionary dynamics and implementing integrative modeling efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Deformation and dynamics of red blood cells in flow through cylindrical microchannels.

PubMed

Fedosov, Dmitry A; Peltomäki, Matti; Gompper, Gerhard

2014-06-28

The motion of red blood cells (RBCs) in microcirculation plays an important role in blood flow resistance and in the cell partitioning within a microvascular network. Different shapes and dynamics of RBCs in microvessels have been previously observed experimentally including the parachute and slipper shapes. We employ mesoscale hydrodynamic simulations to predict the phase diagram of shapes and dynamics of RBCs in cylindrical microchannels, which serve as idealized microvessels, for a wide range of channel confinements and flow rates. A rich dynamical behavior is found, with snaking and tumbling discocytes, slippers performing a swinging motion, and stationary parachutes. We discuss the effects of different RBC states on the flow resistance, and the influence of RBC properties, characterized by the Föppl-von Kármán number, on the shape diagram. The simulations are performed using the same viscosity for both external and internal fluids surrounding a RBC; however, we discuss how the viscosity contrast would affect the shape diagram.

Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance

PubMed Central

Ip, Camilla L. C.; Ansari, M. Azim; Wilson, Daniel J.; Espedido, Bjorn A.; Jensen, Slade O.; Bowden, Rory

2016-01-01

Enterococcus faecium, a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics of E. faecium in a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing. E. faecium was found to be subject to high rates of recombination with little evidence of sequence importation from outside the local E. faecium population. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology of E. faecium nosocomial infections and establishing routes of transmission. Several forms of the Tn1549-like element–vanB gene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances of in situ evolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium with evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient transmission events, underlining the need for careful consideration before modifying current E. faecium infection control strategies. PMID:27713836

Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance.

PubMed

van Hal, Sebastiaan J; Ip, Camilla L C; Ansari, M Azim; Wilson, Daniel J; Espedido, Bjorn A; Jensen, Slade O; Bowden, Rory

2016-01-19

Enterococcus faecium , a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics of E. faecium in a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing. E. faecium was found to be subject to high rates of recombination with little evidence of sequence importation from outside the local E. faecium population. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology of E. faecium nosocomial infections and establishing routes of transmission. Several forms of the Tn 1549 -like element- vanB gene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances of in situ evolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium with evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient transmission events, underlining the need for careful consideration before modifying current E. faecium infection control strategies.

Structural insight of DNA topoisomerases I from camptothecin-producing plants revealed by molecular dynamics simulations.

PubMed

Sirikantaramas, Supaart; Meeprasert, Arthitaya; Rungrotmongkol, Thanyada; Fuji, Hideyoshi; Hoshino, Tyuji; Sudo, Hiroshi; Yamazaki, Mami; Saito, Kazuki

2015-05-01

DNA topoisomerase I (Top1) catalyzes changes in DNA topology by cleaving and rejoining one strand of the double stranded (ds)DNA. Eukaryotic Top1s are the cellular target of the plant-derived anticancer indole alkaloid camptothecin (CPT), which reversibly stabilizes the Top1-dsDNA complex. However, CPT-producing plants, including Camptotheca acuminata, Ophiorrhiza pumila and Ophiorrhiza liukiuensis, are highly resistant to CPT because they possess point-mutated Top1. Here, the adaptive convergent evolution is reported between CPT production ability and mutations in their Top1, as a universal resistance mechanism found in all tested CPT-producing plants. This includes Nothapodytes nimmoniana, one of the major sources of CPT. To obtain a structural insight of the resistance mechanism, molecular dynamics simulations of CPT- resistant and -sensitive plant Top1s complexed with dsDNA and topotecan (a CPT derivative) were performed, these being compared to that for the CPT-sensitive human Top1. As a result, two mutations, Val617Gly and Asp710Gly, were identified in O. pumila Top1 and C. acuminata Top1, respectively. The substitutions at these two positions, surprisingly, are the same as those found in a CPT derivative-resistant human colon adenocarcinoma cell line. The results also demonstrated an increased linker flexibility of the CPT-resistant Top1, providing an additional explanation for the resistance mechanism found in CPT-producing plants. These mutations could reflect the long evolutionary adaptation of CPT-producing plant Top1s to confer a higher degree of resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characteristics of Dynamic Magnetic Resonance Image Enhancement in Prolactinomas Resistant to Dopamine Agonist Therapy

PubMed Central

Guo, Qinghua; Erickson, Bradley J.; Chang, Alice Y.; Erickson, Dana

2015-01-01

Objective To determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, Minnesota). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naïve groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) that showed DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group vs the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P=.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P=.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% CI, 1.07-3.27; P=.02). Conclusions dMRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas. PMID:25551412

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

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

Sun, Hui-Yong; Ji, Feng-Qin, E-mail: fengqinji@mail.hzau.edu.cn; Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070

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 ofmore » 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.« less

Analysis of wind-resistant and stability for cable tower in cable-stayed bridge with four towers

NASA Astrophysics Data System (ADS)

Meng, Yangjun; Li, Can

2017-06-01

Wind speed time history simulation methods have been introduced first, especially the harmonic synthesis method introduced in detail. Second, taking Chishi bridge for example, choosing the particular sections, and combined with the design wind speed, three-component coefficient simulate analysis between -4°and 4°has been carry out with the Fluent software. The results show that drag coefficient reaches maximum when the attack Angle is 1°. According to measured wind speed samples,time history curves of wind speed at bridge deck and tower roof have been obtained,and wind-resistant time history analysis for No.5 tower has been carry out. Their results show that the dynamic coefficients are different with different calculation standard, especially transverse bending moment, pulsating crosswind load does not show a dynamic amplification effect.Under pulsating wind loads at bridge deck or tower roof, the maximum displacement at the top of the tower and the maximum stress at the bottom of the tower are within the allowable range. The transverse stiffness of tower is greater than that of the longitudinal stiffness, therefore wind-resistant analysis should give priority to the longitudinal direction. Dynamic coefficients are different with different standard, the maximum dynamic coefficient should be used for the pseudo-static analysis.Finally, the static stability of tower is analyzed with different load combinations, and the galloping stabilities of cable tower is proved.

Extracellular matrix-associated proteins form an integral and dynamic system during Pseudomonas aeruginosa biofilm development.

PubMed

Zhang, Weipeng; Sun, Jin; Ding, Wei; Lin, Jinshui; Tian, Renmao; Lu, Liang; Liu, Xiaofen; Shen, Xihui; Qian, Pei-Yuan

2015-01-01

Though the essential role of extracellular matrix in biofilm development has been extensively documented, the function of matrix-associated proteins is elusive. Determining the dynamics of matrix-associated proteins would be a useful way to reveal their functions in biofilm development. Therefore, we applied iTRAQ-based quantitative proteomics to evaluate matrix-associated proteins isolated from different phases of Pseudomonas aeruginosa ATCC27853 biofilms. Among the identified 389 proteins, 54 changed their abundance significantly. The increased abundance of stress resistance and nutrient metabolism-related proteins over the period of biofilm development was consistent with the hypothesis that biofilm matrix forms micro-environments in which cells are optimally organized to resist stress and use available nutrients. Secreted proteins, including novel putative effectors of the type III secretion system were identified, suggesting that the dynamics of pathogenesis-related proteins in the matrix are associated with biofilm development. Interestingly, there was a good correlation between the abundance changes of matrix-associated proteins and their expression. Further analysis revealed complex interactions among these modulated proteins, and the mutation of selected proteins attenuated biofilm development. Collectively, this work presents the first dynamic picture of matrix-associated proteins during biofilm development, and provides evidences that the matrix-associated proteins may form an integral and well regulated system that contributes to stress resistance, nutrient acquisition, pathogenesis and the stability of the biofilm.

One-step global parameter estimation of kinetic inactivation parameters for Bacillus sporothermodurans spores under static and dynamic thermal processes.

PubMed

Cattani, F; Dolan, K D; Oliveira, S D; Mishra, D K; Ferreira, C A S; Periago, P M; Aznar, A; Fernandez, P S; Valdramidis, V P

2016-11-01

Bacillus sporothermodurans produces highly heat-resistant endospores, that can survive under ultra-high temperature. High heat-resistant sporeforming bacteria are one of the main causes for spoilage and safety of low-acid foods. They can be used as indicators or surrogates to establish the minimum requirements for heat processes, but it is necessary to understand their thermal inactivation kinetics. The aim of the present work was to study the inactivation kinetics under both static and dynamic conditions in a vegetable soup. Ordinary least squares one-step regression and sequential procedures were applied for estimating these parameters. Results showed that multiple dynamic heating profiles, when analyzed simultaneously, can be used to accurately estimate the kinetic parameters while significantly reducing estimation errors and data collection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structure, Dynamic Cracking Resistance, and Crack Growth Micromechanism in Pipe Billets after Thermomechanical Treatment

NASA Astrophysics Data System (ADS)

Simonov, M. Yu.; Simonov, Yu. N.; Shaimanov, G. S.

2018-01-01

The structure, dynamic cracking resistance, and micromechanisms of crack growth in initially highly tempered pipe billets made of structural carbon steel are studied after thermomechanical treatment, including cold plastic deformation by radial forging followed by annealing, under various conditions. The strength is found to be maximum after cold radial forging followed by annealing at 300°C. Cold radial forging and annealing at 600°C are shown to cause the formation of an ultrafine-grained structure with an average grain/subgrain size of 900 nm. The structural features formed in both the axial and the transverse direction after cold radial forging have been revealed. The mechanism of crack growth after heat treatment and thermomechanical treatment has been studied. The fracture surface elements formed during dynamic-crackingresistance tests have been qualitatively analyzed.

Designing Inter-Organisational Collectivities for Dynamic Fit: Stability, maneuvrability and Application in Disaster Relief Endeavours

DTIC Science & Technology

2011-01-01

changed consumer preferences . Hence, static stability limits initial performance deviation (e.g., maintaining desired airplane altitude, maintaining...by changed consumer preferences . Hence, dynamic stability limits the duration of performance deviation (e.g., maintaining desired airplane altitude...altitude from wind gust. Initial resistance to deviation in profit level from change in consumer preferences . Dynamic stability Quickness of a

The impact of land use change and hydroclimatic variability on landscape connectivity dynamics across surface water networks at subcontinental scale

NASA Astrophysics Data System (ADS)

Tulbure, M. G.; Bishop-Taylor, R.; Broich, M.

2017-12-01

Land use (LU) change and hydroclimatic variability affect spatiotemporal landscape connectivity dynamics, important for species movement and dispersal. Despite the fact that LU change can strongly influence dispersal potential over time, prior research has only focused on the impacts of dynamic changes in the distribution of potential habitats. We used 8 time-steps of historical LU together with a Landsat-derived time-series of surface water habitat dynamics (1986-2011) over the Murray-Darling Basin (MDB), a region with extreme hydroclimatic variability, impacted by LU changes. To assess how changing LU and hydroclimatic variability affect landscape connectivity across time, we compared 4 scenarios, namely one where both climate and LU are dynamic over time, one where climate is kept steady (i.e. a median surface water extent layer), and two scenarios where LU is kept steady (i.e. resistance values associated with the most recent or the first LU layer). We used circuit theory to assign landscape features with `resistance' costs and graph theory network analysis, with surface water habitats as `nodes' connected by dispersal paths or `edges' Findings comparing a dry and an average season show high differences in number of nodes (14581 vs 21544) and resistance distances. The combined effect of LU change and landscape wetness was lower than expected, likely a function of the large, MDB-wide, aggregation scale. Spatially explicit analyses are expected to identify areas where the synergistic effect of LU change and landscape wetness greatly reduce or increase landscape connectivity, as well as areas where the two effects cancel each other out.

Blast and Penetration Resistant Tactical Shelters

DTIC Science & Technology

1979-07-01

2. Hardened Wall Material Properties 32 3. S-280 Shelter Panal Properties 33 4. Results Zor Dynamic Response of Complete S-280 Shelters 32 £-". In...insulation from a -6501 low to a 120 0F high plus a solar heating load 7. Corrosion resistance including salt fog 8. Blackout capability 9. Fungus...65 0 F), high temperature (120 0 F) plus a solar heating (BTU) load. g. Corrosion resistance (salt fog). 19 h. Blackout capability. i. Fungus

Using of porous portion to simulate pulmonary resistance in the computational fluid dynamic models of Fontan connection.

PubMed

Sun, Qi; Liu, Jinlong; Qian, Yi; Hong, Haifa; Liu, Jinfen

2013-01-01

In this study, we performed computational fluid dynamic (CFD) simulations in a patient-specific three-dimensional extracardiac conduit Fontan connection. The pulmonary resistance was incorporated in the CFD model by connecting porous portions in the left and right pulmonary arteries. The pressure in the common atrium was set as boundary conditions at the outlets of the pulmonary arteries. The flow rate in the innominate veins and the inferior vena cava (IVC) was set as inflow boundary conditions. Furthermore, the inflow rate of IVC was increased to 2 and 3 times of that measured to perform another two simulations and the resistance provided by the porous portions was compared among these three conditions. We found out that the pulmonary resistance set as porous portion in the CFD models remains relatively steady despite the change of the inflow rate. We concluded that, in the CFD simulations for the Fontan connections, porous portion could be used to represent pulmonary resistance steadily. The pulmonary resistance and pressure in the common atrium could be acquired directly by clinical examination. The employment of porous portion together with pressure in the common atrium in the CFD model could facilitate and accurate the set of outlet boundary conditions especially for those actual pulmonary flow splits was unpredictable such as virtual operative designs related CFD simulations.

Characteristics of multilevel storage and switching dynamics in resistive switching cell of Al2O3/HfO2/Al2O3 sandwich structure

NASA Astrophysics Data System (ADS)

Liu, Jian; Yang, Huafeng; Ma, Zhongyuan; Chen, Kunji; Zhang, Xinxin; Huang, Xinfan; Oda, Shunri

2018-01-01

We reported an Al2O3/HfO2/Al2O3 sandwich structure resistive switching device with significant improvement of multilevel cell (MLC) operation capability, which exhibited that four stable and distinct resistance states (one low resistance state and three high resistance states) can be achieved by controlling the Reset stop voltages (V Reset-stop) during the Reset operation. The improved MLC operation capability can be attributed to the R HRS/R LRS ratio enhancement resulting from increasing of the series resistance and decreasing of leakage current by inserting two Al2O3 layers. For the high-speed switching applications, we studied the initial switching dynamics by using the measurements of the pulse width and amplitude dependence of Set and Reset switching characteristics. The results showed that under the same pulse amplitude conditions, the initial Set progress is faster than the initial Reset progress, which can be explained by thermal-assisted electric field induced rupture model in the oxygen vacancies conductive filament. Thus, proper combination of varying pulse amplitude and width can help us to optimize the device operation parameters. Moreover, the device demonstrated ultrafast program/erase speed (10 ns) and good pulse switching endurance (105 cycles) characteristics, which are suitable for high-density and fast-speed nonvolatile memory applications.

Dynamic M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high fat diet-induced obesity in mice

USDA-ARS?s Scientific Manuscript database

Chronic inflammation is a pathogenic factor in obesity complications, in particular insulin resistance (IR). A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been the recognition of the underlying role of adipose tissue macrophages (ATM's). The...

New Higher Education President Integration: Change and Resistance Viewed through Social Power Bases and a Change Model Lens

ERIC Educational Resources Information Center

Gearin, Christopher A.

2017-01-01

This study investigates how new presidents of higher education institutions struggle to understand their organisations, paying special attention to campus resistance, and how new presidents manage institutional dynamics and expectations. A qualitative study using a phenomenological approach is conducted with 11 single-campus presidents of…

High-velocity deformation of Al 0.3CoCrFeNi high-entropy alloy: Remarkable resistance to shear failure

DOE PAGES

Li, Z.; Zhao, S.; Diao, H.; ...

2017-02-17

Here, the mechanical behavior of a single phase (fcc) Al 0.3CoCrFeNi high-entropy alloy (HEA) was studied in the low and high strain-rate regimes. The combination of multiple strengthening mechanisms such as solid solution hardening, forest dislocation hardening, as well as mechanical twinning leads to a high work hardening rate, which is significantly larger than that for Al and is retained in the dynamic regime. The resistance to shear localization was studied by dynamically-loading hat-shaped specimens to induce forced shear localization. However, no adiabatic shear band could be observed. It is therefore proposed that the excellent strain hardening ability gives risemore » to remarkable resistance to shear localization, which makes this material an excellent candidate for penetration protection applications such as armors.« less

A dynamical model for bark beetle outbreaks

Treesearch

Vlastimil Krivan; Mark Lewis; Barbara J. Bentz; Sharon Bewick; Suzanne M. Lenhart; Andrew Liebhold

2016-01-01

Tree-killing bark beetles are major disturbance agents affecting coniferous forest ecosystems. The role of environmental conditions on driving beetle outbreaks is becoming increasingly important as global climatic change alters environmental factors, such as drought stress, that, in turn, govern tree resistance. Furthermore, dynamics between beetles and trees...

Assessing thermal conductivity of composting reactor with attention on varying thermal resistance between compost and the inner surface.

PubMed

Wang, Yongjiang; Niu, Wenjuan; Ai, Ping

2016-12-01

Dynamic estimation of heat transfer through composting reactor wall was crucial for insulating design and maintaining a sanitary temperature. A model, incorporating conductive, convective and radiative heat transfer mechanisms, was developed in this paper to provide thermal resistance calculations for composting reactor wall. The mechanism of thermal transfer from compost to inner surface of structural layer, as a first step of heat loss, was important for improving insulation performance, which was divided into conduction and convection and discussed specifically in this study. It was found decreasing conductive resistance was responsible for the drop of insulation between compost and reactor wall. Increasing compost porosity or manufacturing a curved surface, decreasing the contact area of compost and the reactor wall, might improve the insulation performance. Upon modeling of heat transfers from compost to ambient environment, the study yielded a condensed and simplified model that could be used to conduct thermal resistance analysis for composting reactor. With theoretical derivations and a case application, the model was applicable for both dynamic estimation and typical composting scenario. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electromagnetic effects on dynamics of high-beta filamentary structures

DOE PAGES

Lee, Wonjae; Umansky, Maxim V.; Angus, J. R.; ...

2015-01-12

The impacts of the electromagnetic effects on blob dynamics are considered. Electromagnetic BOUT++ simulations on seeded high-beta blobs demonstrate that inhomogeneity of magnetic curvature or plasma pressure along the filament leads to bending of the blob filaments and the magnetic field lines due to increased propagation time of plasma current (Alfvén time). The bending motion can enhance heat exchange between the plasma facing materials and the inner SOL region. The effects of sheath boundary conditions on the part of the blob away from the boundary are also diminished by the increased Alfvén time. Using linear analysis and the BOUT++ simulation,more » it is found that electromagnetic effects in high temperature and high density plasmas reduce the growth rate of resistive drift wave turbulence when resistivity drops below some certain value. Lastly, in the course of blobs motion in the SOL its temperature is reduced, which leads to enhancement of resistive effects, so the blob can switch from electromagnetic to electrostatic regime, where resistive drift wave turbulence become important.« less

Multilevel Resistance Programming in Conductive Bridge Resistive Memory

NASA Astrophysics Data System (ADS)

Mahalanabis, Debayan

This work focuses on the existence of multiple resistance states in a type of emerging non-volatile resistive memory device known commonly as Programmable Metallization Cell (PMC) or Conductive Bridge Random Access Memory (CBRAM), which can be important for applications such as multi-bit memory as well as non-volatile logic and neuromorphic computing. First, experimental data from small signal, quasi-static and pulsed mode electrical characterization of such devices are presented which clearly demonstrate the inherent multi-level resistance programmability property in CBRAM devices. A physics based analytical CBRAM compact model is then presented which simulates the ion-transport dynamics and filamentary growth mechanism that causes resistance change in such devices. Simulation results from the model are fitted to experimental dynamic resistance switching characteristics. The model designed using Verilog-a language is computation-efficient and can be integrated with industry standard circuit simulation tools for design and analysis of hybrid circuits involving both CMOS and CBRAM devices. Three main circuit applications for CBRAM devices are explored in this work. Firstly, the susceptibility of CBRAM memory arrays to single event induced upsets is analyzed via compact model simulation and experimental heavy ion testing data that show possibility of both high resistance to low resistance and low resistance to high resistance transitions due to ion strikes. Next, a non-volatile sense amplifier based flip-flop architecture is proposed which can help make leakage power consumption negligible by allowing complete shutdown of power supply while retaining its output data in CBRAM devices. Reliability and energy consumption of the flip-flop circuit for different CBRAM low resistance levels and supply voltage values are analyzed and compared to CMOS designs. Possible extension of this architecture for threshold logic function computation using the CBRAM devices as re-configurable resistive weights is also discussed. Lastly, Spike timing dependent plasticity (STDP) based gradual resistance change behavior in CBRAM device fabricated in back-end-of-line on a CMOS die containing integrate and fire CMOS neuron circuits is demonstrated for the first time which indicates the feasibility of using CBRAM devices as electronic synapses in spiking neural network hardware implementations for non-Boolean neuromorphic computing.

Modelling density-dependent resistance in insect-pathogen interactions.

PubMed

White, K A; Wilson, K

1999-10-01

We consider a mathematical model for a host-pathogen interaction where the host population is split into two categories: those susceptible to disease and those resistant to disease. Since the model was motivated by studies on insect populations, we consider a discrete-time model to reflect the discrete generations which are common among insect species. Whether an individual is born susceptible or resistant to disease depends on the local population levels at the start of each generation. In particular, we are interested in the case where the fraction of resistant individuals in the population increases as the total population increases. This may be seen as a positive feedback mechanism since disease is the only population control imposed upon the system. Moreover, it reflects recent experimental observations from noctuid moth-baculovirus interactions that pathogen resistance may increase with larval density. We find that the inclusion of a resistant class can stabilise unstable host-pathogen interactions but there is greatest regulation when the fraction born resistant is density independent. Nonetheless, inclusion of density dependence can still allow intrinsically unstable host-pathogen dynamics to be stabilised provided that this effect is sufficiently small. Moreover, inclusion of density-dependent resistance to disease allows the system to give rise to bistable dynamics in which the final outcome is dictated by the initial conditions for the model system. This has implications for the management of agricultural pests using biocontrol agents-in particular, it is suggested that the propensity for density-dependent resistance be determined prior to such a biocontrol attempt in order to be sure that this will result in the prevention of pest outbreaks, rather than their facilitation. Finally we consider how the cost of resistance to disease affects model outcomes and discover that when there is no cost to resistance, the model predicts stable periodic outbreaks of the insect population. The results are interpreted ecologically and future avenues for research to address the shortfalls in the present model system are discussed. Copyright 1999 Academic Press.

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA Technical Reports Server (NTRS)

Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

2012-01-01

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the development of the Adams ARED module including its capabilities, limitations, and assumptions. Preliminary results, validation activities, and a practical application of the module to inform the relative effect of the flywheels on exercise will be discussed.

Dynamics of layered reinforced concrete beam on visco-elastic foundation with different resistances of concrete and reinforcement to tension and compression

NASA Astrophysics Data System (ADS)

Nemirovsky, Y. V.; Tikhonov, S. V.

2018-03-01

Originally, fundamentals of the theory of limit equilibrium and dynamic deformation of building metal and reinforced concrete structures were created by A. A. Gvozdev [1] and developed by his followers [4, 5, 6, 7, 11, 12]. Forming the basis for the calculation, the model of an ideal rigid-plastic material has enabled to determine in many cases the ultimate load bearing capacity and upper (kinematically possible) or lower (statically valid) values for a wide class of different structures with quite simple methods. At the same time, applied to concrete structures the most important property of concrete to significantly differently resist tension and compression was not taken into account [10]. This circumstance was considered in [3] for reinforced concrete beams under conditions of quasistatic loading. The deformation is often accompanied by resistance of the environment in construction practice [8, 9]. In [2], the dynamics of multi-layered concrete beams on visco-elastic foundation under the loadings of explosive type is considered. In this work we consider the case which is often encountered in practical applications when the loadings weakly change in time.

Voltage-ampere characteristics of YBCO coated conductor under inhomogeneous oscillating magnetic field

NASA Astrophysics Data System (ADS)

Geng, J.; Shen, B.; Li, C.; Zhang, H.; Matsuda, K.; Li, J.; Zhang, X.; Coombs, T. A.

2016-06-01

Direct current carrying type II superconductors present a dynamic resistance when subjected to an oscillating magnetic field perpendicular to the current direction. If a superconductor is under a homogeneous field with high magnitude, the dynamic resistance value is nearly independent of transport current. Hoffmann and coworkers [Hoffmann et al., IEEE Trans. Appl. Supercond. 21, 1628 (2011)] discovered, however, flux pumping effect when a superconducting tape is under an inhomogeneous field orthogonal to the tape surface generated by rotating magnets. Following their work, we report the whole Voltage-Ampere (V-I) curves of an YBCO coated conductor under permanent magnets rotating with different frequencies and directions. We discovered that the two curves under opposite rotating directions differ from each other constantly when the transport current is less than the critical current, whereas the difference gradually reduces after the transport current exceeds the critical value. We also find that for different field frequencies, the difference between the two curves decreases faster with lower field frequency. The result indicates that the transport loss is dependent on the relative direction of the transport current and field travelling, which is distinct from traditional dynamic resistance model. The work may be instructive for the design of superconducting motors.

Effects of Peanut-Tobacco Rotations on Population Dynamics of Meloidogyne arenaria in Mixed Race Populations.

PubMed

Hirunsalee, A; Barker, K R; Beute, M K

1995-06-01

A 3-year microplot study was initiated to characterize the population dynamics, reproduction potential, and survivorship of single or mixed populations of Meloidogyne arenaria race 1 (Ma1) and race 2 (Ma2), as affected by crop rotations of peanut 'Florigiant' and M. incognita races 1 and 3-resistant 'McNair 373' and susceptible 'Coker 371-Gold' tobacco. Infection, reproduction, and root damage by Ma2 on peanut and by Ma1 on resistant tobacco were limited in the first year. Infection, reproduction, and root-damage potentials on susceptible tobacco were similar for Ma1 and Ma2. In the mixed (1:1) population, Ma1 was dominant on peanut and Ma2 was dominant on both tobacco cultivars. Crop rotation affected the population dynamics of different nematode races. For years 2 and 3, the low numbers of Ma1 and Ma2 from a previous-year poor host increased rapidly on suitable hosts. Ma1 had greater reproduction factors ([RF] = population density at harvest/population density at preplandng) than did Ma2 and Ma1 + Ma2 in second-year peanut plots following first-year resistant tobacco, and in third-year peanut plots following second-year tobacco. In mixed infestations, Ma1 predominated over Ma2 in previous-year peanut plots, whereas Ma2 predominated over Ma1 in previous-year tobacco plots. Moderate damage on resistant tobacco was induced by Ma1 in the second year. In the third year, moderate damage on peanut was associated with 'Ma2' from previous-year peanut plots. The resistant tobacco supported sufficient reproduction of Ma1 over 2 years to effect moderate damage and yield suppression to peanut in year 3.

Effects of Peanut-Tobacco Rotations on Population Dynamics of Meloidogyne arenaria in Mixed Race Populations

PubMed Central

Hirunsalee, Anan; Barker, K. R.; Beute, M. K.

1995-01-01

A 3-year microplot study was initiated to characterize the population dynamics, reproduction potential, and survivorship of single or mixed populations of Meloidogyne arenaria race 1 (Ma1) and race 2 (Ma2), as affected by crop rotations of peanut 'Florigiant' and M. incognita races 1 and 3-resistant 'McNair 373' and susceptible 'Coker 371-Gold' tobacco. Infection, reproduction, and root damage by Ma2 on peanut and by Ma1 on resistant tobacco were limited in the first year. Infection, reproduction, and root-damage potentials on susceptible tobacco were similar for Ma1 and Ma2. In the mixed (1:1) population, Ma1 was dominant on peanut and Ma2 was dominant on both tobacco cultivars. Crop rotation affected the population dynamics of different nematode races. For years 2 and 3, the low numbers of Ma1 and Ma2 from a previous-year poor host increased rapidly on suitable hosts. Ma1 had greater reproduction factors ([RF] = population density at harvest/population density at preplandng) than did Ma2 and Ma1 + Ma2 in second-year peanut plots following first-year resistant tobacco, and in third-year peanut plots following second-year tobacco. In mixed infestations, Ma1 predominated over Ma2 in previous-year peanut plots, whereas Ma2 predominated over Ma1 in previous-year tobacco plots. Moderate damage on resistant tobacco was induced by Ma1 in the second year. In the third year, moderate damage on peanut was associated with 'Ma2' from previous-year peanut plots. The resistant tobacco supported sufficient reproduction of Ma1 over 2 years to effect moderate damage and yield suppression to peanut in year 3. PMID:19277278

Impact of resistance mutations on inhibitor binding to HIV-1 integrase

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

Chen, Qi; Buolamwini, John K.; Smith, Jeremy C.

2013-11-08

Here, HIV-1 integrase (IN) is essential for HIV-1 replication, catalyzing two key reaction steps termed 3' processing and strand transfer. Therefore, IN has become an important target for antiviral drug discovery. However, mutants have emerged, such as E92Q/N155H and G140S/Q148H, which confer resistance to raltegravir (RAL), the first IN strand transfer inhibitor (INSTI) approved by the FDA, and to the recently approved elvitegravir (EVG). To gain insights into the molecular mechanisms of ligand binding and drug resistance, we performed molecular dynamics (MD) simulations of homology models of the HIV-1 IN and four relevant mutants complexed with viral DNA and RAL.more » The results show that the structure and dynamics of the 140s loop, comprising residues 140 to 149, are strongly influenced by the IN mutations. In the simulation of the G140S/Q148H double mutant, we observe spontaneous dissociation of RAL from the active site, followed by an intrahelical swing-back of the 3' -OH group of nucleotide A17, consistent with the experimental observation that the G140S/Q148H mutant exhibits the highest resistance to RAL compared to other IN mutants. An important hydrogen bond between residues 145 and 148 is present in the wild-type IN but not in the G140S/Q148H mutant, accounting for the structural and dynamical differences of the 140s' loop and ultimately impairing RAL binding in the double mutant. End-point free energy calculations that broadly capture the experimentally known RAL binding profiles elucidate the contributions of the 140s' loop to RAL binding free energies and suggest possible approaches to overcoming drug resistance.« less

Synthesis and activity of a novel diether phosphonoglycerol in phospholipase-resistant synthetic lipid:peptide lung surfactants†

PubMed Central

Schwan, Adrian L.; Singh, Suneel P.; Davy, Jason A.; Waring, Alan J.; Gordon, Larry M.; Walther, Frans J.; Wang, Zhengdong; Notter, Robert H.

2012-01-01

This paper reports the chemical synthesis and purification of a novel phospholipase-resistant C16:0, C16:1 diether phosphonoglycerol with structural analogy to ester-linked anionic phosphatidylglycerol (PG) in endogenous pulmonary surfactant. This diether phosphonoglycerol (PG 1) is studied for phospholipase A2 (PLA2) resistance and for surface activity in synthetic exogenous surfactants combined with Super Mini-B (S-MB) peptide and DEPN-8, a previously-reported diether phosphonolipid analog of dipalmitoyl phosphatidylcholine (DPPC, the major zwitterionic phospholipid in native lung surfactant). Activity experiments measured both adsorption and dynamic surface tension lowering due to the known importance of these surface behaviors in lung surfactant function in vivo. Synthetic surfactants containing 9 : 1 DEPN-8:PG 1 + 3% S-MB were resistant to degradation by PLA2 in chromatographic studies, while calf lung surfactant extract (CLSE, the substance of the bovine clinical surfactant Infasurf®) was significantly degraded by PLA2. The 9 : 1 DEPN-8:PG 1 + 3% S-MB mixture also had small but consistent increases in both adsorption and dynamic surface tension lowering ability compared to DEPN-8 + 3% S-MB. Consistent with these surface activity increases, molecular dynamics simulations using Protein Modeller, GROMACS force-field, and PyMOL showed that bilayers containing DPPC and palmitoyl-oleoyl-PC (POPC) as surrogates of DEPN-8 and PG 1 were penetrated to a greater extent by S-MB peptide than bilayers of DPPC alone. These results suggest that PG 1 or related anionic phosphono-PG analogs may have functional utility in phospholipase-resistant synthetic surfactants targeting forms of acute pulmonary injury where endogenous surfactant becomes dysfunctional due to phospholipase activity in the innate inflammatory response. PMID:22530092

Explosive Magnetic Reconnection in Double-current Sheet Systems: Ideal versus Resistive Tearing Mode

NASA Astrophysics Data System (ADS)

Baty, Hubert

2017-03-01

Magnetic reconnection associated with the tearing instability occurring in double-current sheet systems is investigated within the framework of resistive magnetohydrodynamics (MHD) in a two-dimensional Cartesian geometry. A special emphasis on the existence of fast and explosive phases is taken. First, we extend the recent theory on the ideal tearing mode of a single-current sheet to a double-current layer configuration. A linear stability analysis shows that, in long and thin systems with (length to shear layer thickness) aspect ratios scaling as {S}L9/29 (S L being the Lundquist number based on the length scale L), tearing modes can develop on a fast Alfvénic timescale in the asymptotic limit {S}L\\to ∞ . The linear results are confirmed by means of compressible resistive MHD simulations at relatively high S L values (up to 3× {10}6) for different current sheet separations. Moreover, the nonlinear evolution of the ideal double tearing mode (IDTM) exhibits a richer dynamical behavior than its single-tearing counterpart, as a nonlinear explosive growth violently ends up with a disruption when the two current layers interact trough the merging of plasmoids. The final outcome of the system is a relaxation toward a new state, free of magnetic field reversal. The IDTM dynamics is also compared to the resistive double tearing mode dynamics, which develops in similar systems with smaller aspect ratios, ≳ 2π , and exhibits an explosive secondary reconnection, following an initial slow resistive growth phase. Finally, our results are used to discuss the flaring activity in astrophysical magnetically dominated plasmas, with a particular emphasis on pulsar systems.

Inspiratory High Frequency Airway Oscillation Attenuates Resistive Loaded Dyspnea and Modulates Respiratory Function in Young Healthy Individuals

PubMed Central

Morris, Theresa; Sumners, David Paul; Green, David Andrew

2014-01-01

Direct chest-wall percussion can reduce breathlessness in Chronic Obstructive Pulmonary Disease and respiratory function may be improved, in health and disease, by respiratory muscle training (RMT). We tested whether high-frequency airway oscillation (HFAO), a novel form of airflow oscillation generation can modulate induced dyspnoea and respiratory strength and/or patterns following 5 weeks of HFAO training (n = 20) compared to a SHAM-RMT (conventional flow-resistive RMT) device (n = 15) in healthy volunteers (13 males; aged 20–36 yrs). HFAO causes oscillations with peak-to-peak amplitude of 1 cm H2O, whereas the SHAM-RMT device was identical but created no pressure oscillation. Respiratory function, dyspnoea and ventilation during 3 minutes of spontaneous resting ventilation, 1 minute of maximal voluntary hyperventilation and 1 minute breathing against a moderate inspiratory resistance, were compared PRE and POST 5-weeks of training (2×30 breaths at 70% peak flow, 5 days a week). Training significantly reduced NRS dyspnoea scores during resistive loaded ventilation, both in the HFAO (p = 0.003) and SHAM-RMT (p = 0.005) groups. Maximum inspiratory static pressure (cm H2O) was significantly increased by HFAO training (vs. PRE; p<0.001). Maximum inspiratory dynamic pressure was increased by training in both the HFAO (vs. PRE; p<0.001) and SHAM-RMT (vs. PRE; p = 0.021) groups. Peak inspiratory flow rate (L.s−1) achieved during the maximum inspiratory dynamic pressure manoeuvre increased significantly POST (vs. PRE; p = 0.001) in the HFAO group only. HFAO reduced inspiratory resistive loading–induced dyspnoea and augments static and dynamic maximal respiratory manoeuvre performance in excess of flow-resistive IMT (SHAM-RMT) in healthy individuals without the respiratory discomfort associated with RMT. PMID:24651392

Molecular Dynamics Simulations of Novel Potential Inhibitors for Penicillin Binding Protein 2B of the Resistant 5204 Strain of Streptococcus Pneumoniae.

PubMed

Suvaithenamudhan, Suvaiyarasan; Parthasarathy, Subbiah

2017-01-01

Top five best hit compounds (ZINC59376795, ZINC60175365, ZINC36922620, ZINC39550705 and ZINC36953975) were obtained through our high throughput virtual screening (HTVS) analysis with resistant 5204-PBP2B (5204 Penicillin Binding Protein 2B) and sensitive R6-PBP2B (R6 Penicillin Binding Protein 2B) proteins of Streptococcus pneumoniae. To gain insight in molecular docking and dynamics simulations of these top five best hit compounds with both resistant 5204-PBP2B and sensitive R6-PBP2B targets. We have employed Glide XP docking and molecular dynamics simulations of these five best hit compounds with 5204-PBP2B and R6-PBP2B targets. The stability analysis has been carried out through DFT, prime-MM/GBSA binding free energy, RMSD, RMSF and Principal Component Analysis. The reference drug, penicillin G forms stable complex with sensitive R6-PBP2B protein. Similar stability is observed for the mutant resistant 5204-PBP2B with the top scoring compound ZINC592376795 which implies that this compound may act as an effective potential inhibitor. The compound ZINC59376795 forms a total of five hydrogen bonds with resistant 5204-PBP2B protein of which three are with mutated residues. Similarly, the other four compounds including penicillin G also form hydrogen bonds with mutated residue. The MD simulations and stability analysis of the complexes of wild and mutant forms are evaluated for a trajectory period of 16ns and further MD simulations of ZINC59376795 with resistant 5204-PBP2B and sensitive R6-PBP2B confirmed the stability for 50 ns. These results suggest that the top five best hit compounds are found to be a promising gateway for the further development of anti-pneumococcal therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of multiple resistive shells and transient electromagnetic torque on the dynamics of mode locking in reversed field pinch plasmas

NASA Astrophysics Data System (ADS)

Guo, S. C.; Chu, M. S.

2002-11-01

The effects of multiple resistive shells and transient electromagnetic torque on the dynamics of mode locking in the reversed field pinch (RFP) plasmas are studied. Most RFP machines are equipped with one or more metal shells outside of the vacuum vessel. These shells have finite resistivities. The eddy currents induced in each of the shells contribute to the braking electromagnetic (EM) torque which slows down the plasma rotation. In this work we study the electromagnetic torque acting on the plasma (tearing) modes produced by a system of resistive shells. These shells may consist of several nested thin shells or several thin shells enclosed within a thick shell. The dynamics of the plasma mode is investigated by balancing the EM torque from the resistive shells with the plasma viscous torque. Both the steady state theory and the time-dependent theory are developed. The steady state theory is shown to provide an accurate account of the resultant EM torque if (dω/dt)ω-2≪1 and the time scale of interest is much longer than the response (L/R) time of the shell. Otherwise, the transient theory should be adopted. As applications, the steady state theory is used to evaluate the changes of the EM torque response from the resistive shells in two variants of two RFP machines: (1) modification from Reversed Field Experiment (RFX) [Gnesotto et al., Fusion Eng. Des. 25, 335 (1995)] to the modified RFX: both of them are equipped with one thin shell plus one thick shell; (2) modification from Extrap T2 to Extrap T2R [Brunsell et al., Plasma Phys. Controlled Fusion 43, 1457 (2001)]: both of them are equipped with two thin shells. The transient theory has been applied numerically to study the time evolution of the EM torque during the unlocking of a locked tearing mode in the modified RFX.

Effects of a Resistance Training Intervention on Strength, Power, and Performance in Adolescent Dancers.

PubMed

Dowse, Rebecca A; McGuigan, Mike R; Harrison, Craig

2017-11-01

Dowse, RA, McGuigan, MR, and Harrison, C. Effects of a resistance training intervention on strength, power, and performance in adolescent dancers. J Strength Cond Res XX(X): 000-000, 2017-The aim of this study was to determine whether a 9-week resistance training program could have a significant effect on maximum lower-body strength and power, dynamic balance, and dance performance in adolescent dancers. Twelve competitive adolescent female dancers trained in jazz, ballet, and contemporary were recruited from local dance schools and assigned to a resistance training group (dance experience 9.2 ± 2.4 years; age 14.2 ± 1.9 years; height 155.6 ± 9.1 cm; and mass 48.9 ± 13.8 kg). Anthropometry (height, seated height, mass, and skinfolds), subjective dancing performance, dynamic balance (eyes open [EO] and eyes closed), maximum lower-body strength (isometric midthigh pull), and power (vertical countermovement jump, squat jump, and single-leg countermovement jump) were assessed before and after the 9-week intervention period. Posttesting identified a significant improvement EO overall stability (p = 0.003; effect size [ES] = 0.88), EO anterior-posterior stability (p = 0.003; ES = 0.92), peak force (p < 0.001; ES = 0.61), peak power (p = 0.021; ES = 0.22), and subjective dancing performance (p = 0.008; ES = 0.76). These results were accompanied by a trivial but significant change in mass (p = 0.023; ES = 0.09) that was attributed to growth and no significant change in body fat or the sum of skinfolds. This study demonstrated that resistance training can have a significant effect on dynamic balance, maximum lower-body strength, and power without adversely affecting artistic or esthetic components. The results suggest that incorporating resistance training may enhance strength and power adaptations and manage growth-related changes in adolescent dancers.

A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis.

PubMed

Guo, Qinglan; Weng, Jingwei; Xu, Xiaogang; Wang, Minghua; Wang, Xiaoying; Ye, Xinyu; Wang, Wenning; Wang, Minggui

2010-10-08

The first report on the transferable, plasmid-mediated quinolone-resistance determinant qnrA1 was in 1998. Since then, qnr alleles have been discovered worldwide in clinical strains of Gram-negative bacilli. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein (PRP) family. Several PRP crystal structures have been solved, but little is known about the functional significance of their structural arrangement. We conducted random and site-directed mutagenesis on qnrA1 and on qnrC, a newly identified quinolone-resistance gene from Proteus mirabilis. Many of the Qnr mutants lost their quinolone resistance function. The highly conserved hydrophobic Leu or Phe residues at the center of the pentapeptide repeats are known as i sites, and loss-of-function mutations included replacement of the i site hydrophobic residues with charged residues, replacing the i-2 site, N-terminal to the i residues, with bulky side-chain residues, introducing Pro into the β-helix coil, deletion of the N- and C-termini, and excision of a central coil. Molecular dynamics simulations and homology modeling demonstrated that QnrC overall adopts a stable β-helix fold and shares more similarities with MfpA than with other PRP structures. Based on homology modeling and molecular dynamics simulation, the dysfunctional point mutations introduced structural deformations into the quadrilateral β-helix structure of PRPs. Of the pentapeptides of QnrC, two-thirds adopted a type II β-turn, while the rest adopted type IV turns. A gap exists between coil 2 and coil 3 in the QnrC model structure, introducing a structural flexibility that is similar to that seen in MfpA. The hydrophobic core and the β-helix backbone conformation are important for maintaining the quinolone resistance property of Qnr proteins. QnrC may share structural similarity with MfpA.

The Impact of Cell Density and Mutations in a Model of Multidrug Resistance in Solid Tumors

PubMed Central

Greene, James; Lavi, Orit; Gottesman, Michael M.; Levy, Doron

2016-01-01

In this paper we develop a mathematical framework for describing multidrug resistance in cancer. To reflect the complexity of the underlying interplay between cancer cells and the therapeutic agent, we assume that the resistance level is a continuous parameter. Our model is written as a system of integro-differential equations that are parametrized by the resistance level. This model incorporates the cell-density and mutation dependence. Analysis and simulations of the model demonstrate how the dynamics evolves to a selection of one or more traits corresponding to different levels of resistance. The emerging limit distribution with nonzero variance is the desirable modeling outcome as it represents tumor heterogeneity. PMID:24553772

Evolution of the Pseudomonas aeruginosa Aminoglycoside Mutational Resistome In Vitro and in the Cystic Fibrosis Setting.

PubMed

López-Causapé, Carla; Rubio, Rosa; Cabot, Gabriel; Oliver, Antonio

2018-04-01

Inhaled administration of high doses of aminoglycosides is a key maintenance treatment of Pseudomonas aeruginosa chronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of stepwise high-level tobramycin resistance development in vitro and compared the results with those of isogenic pairs of susceptible and resistant clinical isolates. Resistance development correlated with fusA1 mutations in vitro and in vivo. pmrB mutations, conferring polymyxin resistance, were also frequently selected in vitro In contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed in in vitro evolution experiments. Copyright © 2018 American Society for Microbiology.

[Adaptogenic potentialities of dynamic magnetotherapy in the treatment and prevention of ENT pathology in ailing children].

PubMed

Bolotova, N V; Grinkevich, A V; Grishchenko, T P; Raĭgorodskiĭ, Iu M; Tupkin, V D

2007-01-01

Efficacy of dynamic magnetotherapy (in transcranial and adrenal variants) for treatment of ENT pathology and prevention of its exacerbations is demonstrated in 126 ailing children. Mechanism of action of this magnetotherapy is due to formation of adequate adaptation reactions raising resistance to pathogens.

RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy

PubMed Central

2009-01-01

Background To study the dynamics of wild-type and drug-resistant HIV-1 RT variants, we developed a methodology that follows the fates of individual genomes over time within the viral quasispecies. Single genome sequences were obtained from 3 pigtail macaques infected with a recombinant simian immunodeficiency virus containing the RT coding region from HIV-1 (RT-SHIV) and treated with short-course efavirenz monotherapy 13 weeks post-infection followed by daily combination antiretroviral therapy (ART) beginning at week 17. Bioinformatics tools were constructed to trace individual genomes from the beginning of infection to the end of the treatment. Results A well characterized challenge RT-SHIV inoculum was used to infect three monkeys. The RT-SHIV inoculum had 9 variant subpopulations and the dominant subpopulation accounted for 80% of the total genomes. In two of the three monkeys, the inoculated wild-type virus was rapidly replaced by new wild type variants. By week 13, the original dominant subpopulation in the inoculum was replaced by new dominant subpopulations, followed by emergence of variants carrying known NNRTI resistance mutations. However, during ART, virus subpopulations containing resistance mutations did not outgrow the wide-type subpopulations until a minor subpopulation carrying linked drug resistance mutations (K103N/M184I) emerged. We observed that persistent viremia during ART is primarily made up of wild type subpopulations. We also found that subpopulations carrying the V75L mutation, not known to be associated with NNRTI resistance, emerged initially in week 13 in two macaques. Eventually, all subpopulations from these two macaques carried the V75L mutation. Conclusion This study quantitatively describes virus evolution and population dynamics patterns in an animal model. The fact that wild type subpopulations remained as dominant subpopulations during ART treatment suggests that the presence or absence of at least some known drug resistant mutations may not greatly affect virus replication capacity in vivo. Additionally, the emergence and prevalence of V75L indicates that this mutation may provide the virus a selective advantage, perhaps escaping the host immure system surveillance. Our new method to quantitatively analyze viral population dynamics enabled us to observe the relative competitiveness and adaption of different viral variants and provided a valuable tool for studying HIV subpopulation emergence, persistence, and decline during ART. PMID:19889213

The genetic basis of the fitness costs of antimicrobial resistance: a meta-analysis approach.

PubMed

Vogwill, Tom; MacLean, R Craig

2015-03-01

The evolution of antibiotic resistance carries a fitness cost, expressed in terms of reduced competitive ability in the absence of antibiotics. This cost plays a key role in the dynamics of resistance by generating selection against resistance when bacteria encounter an antibiotic-free environment. Previous work has shown that the cost of resistance is highly variable, but the underlying causes remain poorly understood. Here, we use a meta-analysis of the published resistance literature to determine how the genetic basis of resistance influences its cost. We find that on average chromosomal resistance mutations carry a larger cost than acquiring resistance via a plasmid. This may explain why resistance often evolves by plasmid acquisition. Second, we find that the cost of plasmid acquisition increases with the breadth of its resistance range. This suggests a potentially important limit on the evolution of extensive multidrug resistance via plasmids. We also find that epistasis can significantly alter the cost of mutational resistance. Overall, our study shows that the cost of antimicrobial resistance can be partially explained by its genetic basis. It also highlights both the danger associated with plasmidborne resistance and the need to understand why resistance plasmids carry a relatively low cost.

An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine.

PubMed

Bhakat, Soumendranath; Martin, Alberto J M; Soliman, Mahmoud E S

2014-08-01

The emergence of different drug resistant strains of HIV-1 reverse transcriptase (HIV RT) remains of prime interest in relation to viral pathogenesis as well as drug development. Amongst those mutations, M184V was found to cause a complete loss of ligand fitness. In this study, we report the first account of the molecular impact of M184V mutation on HIV RT resistance to 3TC (lamivudine) using an integrated computational approach. This involved molecular dynamics simulation, binding free energy analysis, principle component analysis (PCA) and residue interaction networks (RINs). Results clearly confirmed that M184V mutation leads to steric conflict between 3TC and the beta branched side chain of valine, decreases the ligand (3TC) binding affinity by ∼7 kcal mol(-1) when compared to the wild type, changes the overall conformational landscape of the protein and distorts the native enzyme residue-residue interaction network. The comprehensive molecular insight gained from this study should be of great importance in understanding drug resistance against HIV RT as well as assisting in the design of novel reverse transcriptase inhibitors with high ligand efficacy on resistant strains.

Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase.

PubMed

Chen, Qi; Cheng, Xiaolin; Wei, Dongqing; Xu, Qin

2015-03-01

Although Elvitegravir (EVG) is a newly developed antiretrovirals drug to treat the acquired immunodeficiency syndrome (AIDS), drug resistance has already been found in clinic, such as E92Q/N155H and Q148H/G140S. Several structural investigations have already been reported to reveal the molecular mechanism of the drug resistance. As full length crystal structure for HIV-1 integrase is still unsolved, we herein use the crystal structure of the full length prototype foamy virus (PFV) in complex with virus DNA and inhibitor Elvitegravir as a template to construct the wild type and E92Q/N155H mutant system of HIV-1 integrase. Molecular dynamic simulations was used to revel the binding mode and the drug resistance of the EVG ligand in E92Q/N155H. Several important interactions were discovered between the mutated residues and the residues in the active site of the E92Q/N155H double mutant pattern, and cross correlation and clustering methods were used for detailed analysis. The results from the MD simulation studies will be used to guide the experimental efforts of developing novel inhibitors against drug-resistant HIV integrase mutants.

Functional Resistance to Recurrent Spatially Heterogeneous Disturbances Is Facilitated by Increased Activity of Surviving Bacteria in a Virtual Ecosystem

PubMed Central

König, Sara; Worrich, Anja; Banitz, Thomas; Harms, Hauke; Kästner, Matthias; Miltner, Anja; Wick, Lukas Y.; Frank, Karin; Thullner, Martin; Centler, Florian

2018-01-01

Bacterial degradation of organic compounds is an important ecosystem function with relevance to, e.g., the cycling of elements or the degradation of organic contaminants. It remains an open question, however, to which extent ecosystems are able to maintain such biodegradation function under recurrent disturbances (functional resistance) and how this is related to the bacterial biomass abundance. In this paper, we use a numerical simulation approach to systematically analyze the dynamic response of a microbial population to recurrent disturbances of different spatial distribution. The spatially explicit model considers microbial degradation, growth, dispersal, and spatial networks that facilitate bacterial dispersal mimicking effects of mycelial networks in nature. We find: (i) There is a certain capacity for high resistance of biodegradation performance to recurrent disturbances. (ii) If this resistance capacity is exceeded, spatial zones of different biodegradation performance develop, ranging from no or reduced to even increased performance. (iii) Bacterial biomass and biodegradation dynamics respond inversely to the spatial fragmentation of disturbances: overall biodegradation performance improves with increasing fragmentation, but bacterial biomass declines. (iv) Bacterial dispersal networks can enhance functional resistance against recurrent disturbances, mainly by reactivating zones in the core of disturbed areas, even though this leads to an overall reduction of bacterial biomass. PMID:29696013

The plant host pathogen interface: cell wall and membrane dynamics of pathogen-induced responses.

PubMed

Day, Brad; Graham, Terry

2007-10-01

Perception of pathogens by their hosts is the outcome of a highly coordinated and sophisticated surveillance network, tightly regulated by both host and pathogen elicitors, effectors, and signaling processes. In this article, we focus on two relatively well-studied host-pathogens systems, one involving a bacterial-plant interaction (Pseudomonas syringae-Arabidopsis) and the other involving an oomycete-plant interaction (Phytophthora sojae-soybean). We discuss the status of current research related to events occurring at the host-pathogen interface in these two systems, and how these events influence the organization and activation of resistance responses in the respective hosts. This recent research has revealed that in addition to the previously identified resistance machinery (R-proteins, molecular chaperones, etc.), the dynamics of the cell wall, membrane trafficking, and the actin cytoskeleton are intimately associated with the activation of resistance in plants. Specifically, in Arabidopsis, a possible connection between the actin machinery and R-protein- mediated induction of disease resistance is described. In the case of the P. sojae-soybean interaction, we describe the fact that a classical basal resistance elicitor, the cell wall glucan elicitor from the pathogen, can directly activate host hypersensitive cell death, which is apparently modulated in a race-specific manner by the presence of R genes in the host.

Genetic diversity, transmission dynamics and drug resistance of Mycobacterium tuberculosis in Angola.

PubMed

Perdigão, João; Clemente, Sofia; Ramos, Jorge; Masakidi, Pedro; Machado, Diana; Silva, Carla; Couto, Isabel; Viveiros, Miguel; Taveira, Nuno; Portugal, Isabel

2017-02-23

Tuberculosis (TB) poses a serious public health problem in Angola. No surveillance data on drug resistance is available and nothing is known regarding the genetic diversity and population structure of circulating Mycobacterium tuberculosis strains. Here, we have genotyped and evaluated drug susceptibility of 89 Mycobacterium tuberculosis clinical isolates from Luanda. Thirty-three different spoligotype profiles corresponding to 24 different Shared International Types (SIT) and 9 orphan profiles were detected. SIT 20 (LAM1) was the most prevalent (n = 16, 18.2%) followed by SIT 42 (LAM9; n = 15, 17.1%). Overall, the M. tuberculosis population structure in this sample was dominated by LAM (64.8%) and T (33.0%) strains. Twenty-four-loci MIRU-VNTR analysis revealed that a total of 13 isolates were grouped in 5 distinct clusters. Drug susceptibility data showed that 22 (24.7%) of the 89 clinical isolates were resistant to one or more antibacillary drugs of which 4 (4.5%) were multidrug resistant. In conclusion, this study demonstrates a high predominance of LAM strains circulating in the Luanda setting and the presence of recent transmission events. The rate and the emergence dynamics of drug resistant TB found in this sample are significant and highlight the need of further studies specifically focused on MDR-TB transmission.

New Insights into the In Silico Prediction of HIV Protease Resistance to Nelfinavir

PubMed Central

Antunes, Dinler A.; Rigo, Maurício M.; Sinigaglia, Marialva; de Medeiros, Rúbia M.; Junqueira, Dennis M.; Almeida, Sabrina E. M.; Vieira, Gustavo F.

2014-01-01

The Human Immunodeficiency Virus type 1 protease enzyme (HIV-1 PR) is one of the most important targets of antiretroviral therapy used in the treatment of AIDS patients. The success of protease-inhibitors (PIs), however, is often limited by the emergence of protease mutations that can confer resistance to a specific drug, or even to multiple PIs. In the present study, we used bioinformatics tools to evaluate the impact of the unusual mutations D30V and V32E over the dynamics of the PR-Nelfinavir complex, considering that codons involved in these mutations were previously related to major drug resistance to Nelfinavir. Both studied mutations presented structural features that indicate resistance to Nelfinavir, each one with a different impact over the interaction with the drug. The D30V mutation triggered a subtle change in the PR structure, which was also observed for the well-known Nelfinavir resistance mutation D30N, while the V32E exchange presented a much more dramatic impact over the PR flap dynamics. Moreover, our in silico approach was also able to describe different binding modes of the drug when bound to different proteases, identifying specific features of HIV-1 subtype B and subtype C proteases. PMID:24498124

Pre-existence and emergence of drug resistance in a generalized model of intra-host viral dynamics.

PubMed

Alexander, Helen K; Bonhoeffer, Sebastian

2012-12-01

Understanding the source of drug resistance emerging within a treated patient is an important problem, from both clinical and basic evolutionary perspectives. Resistant mutants may arise de novo either before or after treatment is initiated, with different implications for prevention. Here we investigate this problem in the context of chronic viral diseases, such as human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV and HCV). We present a unified model of viral population dynamics within a host, which can capture a variety of viral life cycles. This allows us to identify which results generalize across various viral diseases, and which are sensitive to the particular virus's life cycle. Accurate analytical approximations are derived that allow for a solid understanding of the parameter dependencies in the system. We find that the mutation-selection balance attained prior to treatment depends on the step at which mutations occur and the viral trait that incurs the cost of resistance. Life cycle effects and key parameters, including mutation rate, infected cell death rate, cost of resistance, and drug efficacy, play a role in determining when mutations arising during treatment are important relative to those pre-existing. Copyright © 2012 Elsevier B.V. All rights reserved.

Structures to Resist the Effects of Accidental Explosions. Volume 3. Principles of Dynamic Analysis

DTIC Science & Technology

1984-06-01

multi-degree-of-freedom systems) is presented. A step-by-step numerical integration of an element’s motion under dynamic loads using the...structural arrangements; providing closures, and preventing damage to interior portions of structures due to structual motion , shock, and fragment...an element’s motion under dynamic loads utilizing the Acceleration-Impulse- Extrapolation Method or the Average Acceleration Method and design charts

Dynamic analysis of a long span, cable-stayed freeway bridge using NASTRAN

NASA Technical Reports Server (NTRS)

Salus, W. L.; Jones, R. E.; Ice, M. W.

1973-01-01

The dynamic analysis for earthquake- and wind-induced response of a long span, cable-stayed freeway bridge by NASTRAN in conjunction with post-processors is described. Details of the structural modeling, the input data generation, and numerical results are given. The influence of the dynamic analysis on the bridge design is traced from the project initiation to the development of a successful earthquake and wind resistant configuration.

The finite state projection approach to analyze dynamics of heterogeneous populations

NASA Astrophysics Data System (ADS)

Johnson, Rob; Munsky, Brian

2017-06-01

Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity. The finite state projection (FSP) approach has often been used to analyze the statistics of independent cells. Here, we extend the FSP analysis to explore the coupling of cell dynamics and biomolecule dynamics within a population. This extension allows a general framework with which to model the state occupations of a heterogeneous, isogenic population of dividing and expiring cells. The method is demonstrated with a simple model of cell-cycle progression, which we use to explore possible dynamics of drug resistance phenotypes in dividing cells. We use this method to show how stochastic single-cell behaviors affect population level efficacy of drug treatments, and we illustrate how slight modifications to treatment regimens may have dramatic effects on drug efficacy.

Probabilistic Dynamic Buckling of Smart Composite Shells

NASA Technical Reports Server (NTRS)

Abumeri, Galib H.; Chamis, Christos C.

2003-01-01

A computational simulation method is presented to evaluate the deterministic and nondeterministic dynamic buckling of smart composite shells. The combined use of composite mechanics, finite element computer codes, and probabilistic analysis enable the effective assessment of the dynamic buckling load of smart composite shells. A universal plot is generated to estimate the dynamic buckling load of composite shells at various load rates and probabilities. The shell structure is also evaluated with smart fibers embedded in the plies right below the outer plies. The results show that, on the average, the use of smart fibers improved the shell buckling resistance by about 10 percent at different probabilities and delayed the buckling occurrence time. The probabilistic sensitivities results indicate that uncertainties in the fiber volume ratio and ply thickness have major effects on the buckling load while uncertainties in the electric field strength and smart material volume fraction have moderate effects. For the specific shell considered in this evaluation, the use of smart composite material is not recommended because the shell buckling resistance can be improved by simply re-arranging the orientation of the outer plies, as shown in the dynamic buckling analysis results presented in this report.

Probabilistic Dynamic Buckling of Smart Composite Shells

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Abumeri, Galib H.

2007-01-01

A computational simulation method is presented to evaluate the deterministic and nondeterministic dynamic buckling of smart composite shells. The combined use of intraply hybrid composite mechanics, finite element computer codes, and probabilistic analysis enable the effective assessment of the dynamic buckling load of smart composite shells. A universal plot is generated to estimate the dynamic buckling load of composite shells at various load rates and probabilities. The shell structure is also evaluated with smart fibers embedded in the plies right next to the outer plies. The results show that, on the average, the use of smart fibers improved the shell buckling resistance by about 10% at different probabilities and delayed the buckling occurrence time. The probabilistic sensitivities results indicate that uncertainties in the fiber volume ratio and ply thickness have major effects on the buckling load while uncertainties in the electric field strength and smart material volume fraction have moderate effects. For the specific shell considered in this evaluation, the use of smart composite material is not recommended because the shell buckling resistance can be improved by simply re-arranging the orientation of the outer plies, as shown in the dynamic buckling analysis results presented in this report.

A Comparison of Whole-Body Vibration and Resistance Training on Total Work in the Rotator Cuff

PubMed Central

Hand, Jason; Verscheure, Susan; Osternig, Louis

2009-01-01

Abstract Context: Whole-body vibration machines are a relatively new technology being implemented in the athletic setting. Numerous authors have examined the proposed physiologic mechanisms of vibration therapy and performance outcomes. Changes have mainly been observed in the lower extremity after individual exercises, with minimal attention to the upper extremity and resistance training programs. Objective: To examine the effects of a novel vibration intervention directed at the upper extremity as a precursor to a supervised, multijoint dynamic resistance training program. Design: Randomized controlled trial. Setting: National Collegiate Athletic Association Division IA institution. Patients or Other Participants: Thirteen female student-athletes were divided into the following 2 treatment groups: (1) whole-body vibration and resistance training or (2) resistance training only. Intervention(s): Participants in the vibration and resistance training group used an experimental vibration protocol of 2 × 60 seconds at 4 mm and 50 Hz, in a modified push-up position, 3 times per week for 10 weeks, just before their supervised resistance training session. Main Outcome Measure(s): Isokinetic total work measurements of the rotator cuff were collected at baseline and at week 5 and week 10. Results: No differences were found between the treatment groups (P > .05). However, rotator cuff output across time increased in both groups (P < .05). Conclusions: Although findings did not differ between the groups, the use of whole-body vibration as a precursor to multijoint exercises warrants further investigation because of the current lack of literature on the topic. Our results indicate that indirectly strengthening the rotator cuff using a multijoint dynamic resistance training program is possible. PMID:19771284

System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors

NASA Astrophysics Data System (ADS)

Nikolai Aljuri, A.; Bursac, Nenad; Marini, Robert; Cohen, Richard J.

2001-08-01

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals.

Dynamical Negative Differential Resistance in Antiferromagnetically Coupled Few-Atom Spin Chains

NASA Astrophysics Data System (ADS)

Rolf-Pissarczyk, Steffen; Yan, Shichao; Malavolti, Luigi; Burgess, Jacob A. J.; McMurtrie, Gregory; Loth, Sebastian

2017-11-01

We present the appearance of negative differential resistance (NDR) in spin-dependent electron transport through a few-atom spin chain. A chain of three antiferromagnetically coupled Fe atoms (Fe trimer) was positioned on a Cu2 N /Cu (100 ) surface and contacted with the spin-polarized tip of a scanning tunneling microscope, thus coupling the Fe trimer to one nonmagnetic and one magnetic lead. Pronounced NDR appears at the low bias of 7 mV, where inelastic electron tunneling dynamically locks the atomic spin in a long-lived excited state. This causes a rapid increase of the magnetoresistance between the spin-polarized tip and Fe trimer and quenches elastic tunneling. By varying the coupling strength between the tip and Fe trimer, we find that in this transport regime the dynamic locking of the Fe trimer competes with magnetic exchange interaction, which statically forces the Fe trimer into its high-magnetoresistance state and removes the NDR.

Rapid evolutionary dynamics in a 2.8-Mb chromosomal region containing multiple prolamin and resistance gene families in Aegilops tauschii

USDA-ARS?s Scientific Manuscript database

The prolamin (seed storage proteins high in glutamine and proline) and resistance gene families are important in domesticated bread wheat (Triticum aestivum) food uses and in defense against pathogen attacks, respectively. To better understand the evolution of these multi-gene families, the DNA se...

Resistance, Resilience and Social Identities: Reframing "Problem Youth" and the Problem of Schooling

ERIC Educational Resources Information Center

Bottrell, Dorothy

2007-01-01

This paper explores the experiences of young people on a public housing estate in inner-city Sydney. Their relations to schooling, truancy and participation in the illicit activities of the local youth network are framed as resistances, as necessary identity work, given the context of their marginalisation. In their explication of the dynamics of…

TNFα dynamics during the oral glucose tolerance test vary according to the level of insulin resistance in pregnant women.

PubMed

Guillemette, Laetitia; Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Moreau, Julie; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2014-05-01

TNFα is suspected to play a role in inflammation and insulin resistance leading to higher risk of metabolic impairment. Controversies exist concerning the role of TNFα in gestational insulin resistance. We investigated the interrelations between TNFα and insulin resistance in a large population-based cohort of pregnant women. Women (n = 756) were followed prospectively at 5-16 weeks and 24-28 weeks of pregnancy. Anthropometric measures and blood samples were collected at both visits. A 75-g oral glucose tolerance test (OGTT) was conducted at the second trimester to assess insulin sensitivity status (homeostasis model of assessment of insulin resistance and Matsuda index). TNFα was measured at the first trimester (nonfasting) and at each time point of the OGTT. Participants were 28.4 ± 4.4 years old and had a mean body mass index of 25.5 ± 5.5 kg/m(2) at first trimester. Median TNFα levels were 1.56 (interquartile range, 1.18-2.06) pg/mL at first trimester and 1.61 (interquartile range, 1.12-2.13) pg/mL at second trimester (1 h after glucose load). At second trimester, higher TNFα levels were associated with higher insulin resistance index levels (r = 0.37 and -0.30 for homeostasis model of assessment of insulin resistance and Matsuda index, respectively; P < .0001), even after adjustment for age, body mass index, triglycerides, and adiponectin. Women with higher insulin resistance showed a continuing decrease in TNFα levels during the OGTT, whereas women who were more insulin sensitive showed an increase in TNFα at hour 1 and a decrease at hour 2 of the test. Higher insulin resistance is associated with higher levels of circulating TNFα at first and second trimesters of pregnancy. TNFα level dynamics during an OGTT at second trimester vary according to insulin-resistance state.

The impact of insecticide applications on the dynamics of resistance: The case of four Aedes aegypti populations from different Brazilian regions

PubMed Central

Martins, Ademir de Jesus; Maciel-de-Freitas, Rafael; Linss, Jutta Gerlinde Birggitt; Araújo, Simone Costa; Lima, José Bento Pereira; Valle, Denise

2018-01-01

Background In the tropics, the utilization of insecticides is still an important strategy for controlling Aedes aegypti, the principle vector of dengue, chikungunya and Zika viruses. However, increasing insecticide resistance in Ae. aegypti populations might hinder insecticide efficacy on a long-term basis. It will be important to understand the dynamics and evolution of insecticide resistance by assessing its frequency and the mechanisms by which it occurs. Methodology/Principal findings The insecticide resistance status of four Brazilian Ae. aegypti populations was monitored. Quantitative bioassays with the major insecticides employed in the country was performed: the adulticide deltamethrin (a pyrethroid—PY) and the larvicides, temephos (an organophosphate) and diflubenzuron (a chitin synthesis inhibitor). Temephos resistance was detected in all populations although exhibiting a slight decrease over time probably due to the interruption of field use. All vector populations were susceptible to diflubenzuron, recently introduced in the country to control Ae. aegypti. Resistance against deltamethrin was extremely high in three populations. Molecular assays investigated substitutions in the voltage gated sodium channel (NaV), the PY target site, at positions 1011, 1016 and 1534. Elevated frequencies of substitutions Val1016Ile and Phe1534Cys related to high PY resistance levels were identified. Biochemical assays detected alterations in the activities of two detoxifying enzyme classes related to metabolic resistance, glutathion-S-transferases and esterases. The results obtained were evaluated in the context of both recent insecticide use and the records of dengue incidence in each locality. Conclusions/Significance The four Ae. aegypti populations evaluated were resistant to the neurotoxic insecticides, temephos and deltamethrin. However, they were still susceptible to diflubenzuron. A probable correlation between adult insect resistance to PY and the domestic application of insecticides is discussed, pointing to the need for awareness measures regarding the correct utilization by citizens. This work aims to contribute to the efficient and rational management of Ae. aegypti control of both larvae and adults. PMID:29432488

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

PubMed Central

Ginevra, Christophe; Jacotin, Nathalie; Forey, Françoise; Chastang, Joëlle; Kay, Elisabeth; Etienne, Jerome; Lina, Gérard; Doublet, Patricia; Jarraud, Sophie

2017-01-01

ABSTRACT Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy, but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila. Twelve independent lineages from a common susceptible L. pneumophila ancestral strain were propagated under conditions of erythromycin or azithromycin pressure to produce high-level macrolide resistance. Whole-genome sequencing was performed on 12 selected clones, and we investigated mutations common to all lineages. We reconstructed the dynamics of mutation for each lineage and demonstrated their involvement in decreased susceptibility to macrolides. The resistant mutants were produced in a limited number of passages to obtain a 4,096-fold increase in erythromycin MICs. Mutations affected highly conserved 5-amino-acid regions of L4 and L22 ribosomal proteins and of domain V of 23S rRNA (G2057, A2058, A2059, and C2611 nucleotides). The early mechanisms mainly affected L4 and L22 proteins and induced a 32-fold increase in the MICs of the selector drug. Additional mutations related to 23S rRNA mostly occurred later and were responsible for a major increase of macrolide MICs, depending on the mutated nucleotide, the substitution, and the number of mutated genes among the three rrl copies. The major mechanisms of the decreased susceptibility to macrolides in L. pneumophila and their dynamics were determined. The results showed that macrolide resistance could be easily selected in L. pneumophila and warrant further investigations in both clinical and environmental settings. PMID:28069647

Relationship Between Respiratory Dynamics and Body Mass Index in Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA) and Comparison Between Lithotomy and Supine Positions

PubMed Central

Zhao, Xiao; Huang, Shiwei; Wang, Zhaomin; Chen, Lianhua; Li, Shitong

2016-01-01

Background This study aimed to compare respiratory dynamics in patients undergoing general anesthesia with a laryngeal mask airway (LMA) in lithotomy and supine positions and to validate the impact of operational position on effectiveness of LMA ventilation. Material/Methods A total of 90 patients (age range, 18–65 years) who underwent general anesthesia were selected and divided into supine position (SP group) and lithotomy position groups (LP group). Vital signs and respiratory dynamic parameters of the 2 groups were measured at different time points and after implantation of an LMA. The arterial blood gas was monitored at 15 min after induction. The intraoperative changes of hemodynamic indexes and postoperative adverse reactions of LMA were recorded. The possible correlation between body mass index (BMI) and respiratory dynamic indexes was analyzed. Results With prolonged duration of the operation, the inspiratory plateau pressure (Pplat), inspiratory resistance (RI), and work of breathing (WOB) gradually increased, while chest-lung compliance (Compl) and partial pressure of carbon dioxide in end-expiratory gas (PetCO2) gradually decreased (all P value <0.05). The mean airway pressure (Pmean), Pplat, and expiratory resistance (Re) in the LP group were significantly higher than in the SP group (P<0.05), while the peak inspiratory flow (FImax), peak expiratory flow (FEmax), WOB, and Compl in the LP group were significantly lower than in the SP group (P<0.05). BMI was positively correlated with peak airway pressure (PIP/Ppeak), Pplat, and airway resistance (Raw) and was negatively correlated with Compl; the differences among patients in lithotomy position were more remarkable (P<0.05). Conclusions The inspiratory plateau pressure and airway resistance increased with prolonged duration of the operation, accompanied by decreased chest-lung compliance. Peak airway pressure and airway resistance were positively correlated with BMI, and chest-lung compliance was negatively correlated with BMI. Changes among patients in lithotomy position were more remarkable than those in supine position. PMID:27476762

“Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice

PubMed Central

Swenson, Luke C.; Pollock, Graham; Wynhoven, Brian; Mo, Theresa; Dong, Winnie; Hogg, Robert S.; Montaner, Julio S. G.; Harrigan, P. Richard

2011-01-01

Background ‘Virtual’ or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. Methods All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the “dynamic range” (defined here by the 10th and 90th percentiles for fold-change in IC50 amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort. Results The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC50 of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small “dynamic ranges” with values of <4-fold change observed in >99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges. Conclusion We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner. PMID:21390218

Application of a sodium sulfur cell with dynamic sulfur electrode to a battery system

NASA Astrophysics Data System (ADS)

Tokoi, H.; Takahashi, K.; Shimoyashiki, S.

1992-01-01

The construction and performance of a sodium sulfur battery system with dynamic sulfur electrodes are described. Three cells were first connected in parallel, then two such groups were connected in series. Each cell included a liquid sodium-filled beta-double-prime-alumina tube and a system to feed liquid sulfur into the annular cathode. Low-resistance graphite felt was tightly packed around the beta-double-prime-alumina tube. Sodium pentasulfide was removed from the sulfur electrode. The battery was operated automatically and stably charged and discharged in the two-phase region. The discharged energy was 4372 Wh (capacity 1170 Ah) during a continuous operation of 19.5 h. The discharge/charge energy efficiency of the battery was 82 percent at an averaged current density of 100 mA/sq cm and operating temperature of 350 C. The deviation of the cell current in a parallel chain was less than 7 percent, and this was induced by the difference in internal resistance. In the daily charge/discharge cycle, cell capacity with the dynamic sulfur electrode was 1.5 times higher than that with the static sulfur electrode using the same active surface of beta-double-prime-alumina, because the internal resistance of the former cell was constant regardless of cell capacity. This battery system with a dynamic sulfur electrode can be applied to energy storage systems,such as large scale load leveling systems, electric vehicle batteries, and solar energy systems.

Genetic diversity, QoI fungicide resistance, and mating type distribution of Cercospora sojina—Implications for the disease dynamics of frogeye leaf spot on soybean

PubMed Central

Shrestha, Sandesh Kumar; Cochran, Alicia; Mengistu, Alemu; Castro-Rocha, Arturo; Young-Kelly, Heather

2017-01-01

Frogeye leaf spot (FLS), caused by Cercospora sojina, causes significant damage to soybean in the U.S. One control strategy is the use of quinone outside inhibitor (QoI) fungicides. QoI resistant isolates were first reported in Tennessee (TN) in 2010. To investigate the disease dynamics of C. sojina, we collected 437 C. sojina isolates in 2015 from Jackson and Milan, TN and used 40 historical isolates collected from 2006–2009 from TN and ten additional states for comparison. A subset of 186 isolates, including historical isolates, were genotyped for 49 single nucleotide polymorphism (SNP) markers and the QoI resistance locus, revealing 35 unique genotypes. The genotypes clustered into three groups with two groups containing only sensitive isolates and the remaining group containing all resistant isolates and a dominant clonal lineage of 130 isolates. All 477 C. sojina isolates were genotyped for the QoI locus revealing 344 resistant and 133 sensitive isolates. All isolates collected prior to 2015 were QoI sensitive. Both mating type alleles (MAT1-1-1 and MAT1-2) were found in Jackson and Milan, TN and recovered from single lesions suggesting sexual recombination may play a role in the epidemiology of field populations. Analysis of C. sojina isolates using SNP markers proved useful to investigate population diversity and to elaborate on diversity as it relates to QoI resistance and mating type. PMID:28486517

The TLR4 Agonist Monophosphoryl Lipid A Drives Broad Resistance to Infection via Dynamic Reprogramming of Macrophage Metabolism.

PubMed

Fensterheim, Benjamin A; Young, Jamey D; Luan, Liming; Kleinbard, Ruby R; Stothers, Cody L; Patil, Naeem K; McAtee-Pereira, Allison G; Guo, Yin; Trenary, Irina; Hernandez, Antonio; Fults, Jessica B; Williams, David L; Sherwood, Edward R; Bohannon, Julia K

2018-06-01

Monophosphoryl lipid A (MPLA) is a clinically used TLR4 agonist that has been found to drive nonspecific resistance to infection for up to 2 wk. However, the molecular mechanisms conferring protection are not well understood. In this study, we found that MPLA prompts resistance to infection, in part, by inducing a sustained and dynamic metabolic program in macrophages that supports improved pathogen clearance. Mice treated with MPLA had enhanced resistance to infection with Staphylococcus aureus and Candida albicans that was associated with augmented microbial clearance and organ protection. Tissue macrophages, which exhibited augmented phagocytosis and respiratory burst after MPLA treatment, were required for the beneficial effects of MPLA. Further analysis of the macrophage phenotype revealed that early TLR4-driven aerobic glycolysis was later coupled with mitochondrial biogenesis, enhanced malate shuttling, and increased mitochondrial ATP production. This metabolic program was initiated by overlapping and redundant contributions of MyD88- and TRIF-dependent signaling pathways as well as downstream mTOR activation. Blockade of mTOR signaling inhibited the development of the metabolic and functional macrophage phenotype and ablated MPLA-induced resistance to infection in vivo. Our findings reveal that MPLA drives macrophage metabolic reprogramming that evolves over a period of days to support a macrophage phenotype highly effective at mediating microbe clearance and that this results in nonspecific resistance to infection. Copyright © 2018 by The American Association of Immunologists, Inc.

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

PubMed

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

2018-07-01

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.

Coalescence of Magnetic Islands in the low resistivity Hall MHD Regime.

NASA Astrophysics Data System (ADS)

Knoll, D. A.; Chacon, L.; Simakov, A. N.

2006-10-01

We revisit the well-known problem of the coalescence of magnetic islands in the context of Hall MHD. Unlike previous work, we focus on regimes of small resistivity (S ˜10^6) and where the ion skin depth diL (system size). These conditions are of relevance, for instance, in the solar corona and the earth's magnetotail. We aim to address under which conditions such systems can exhibit fast reconnection. First, we revisit the resistive MHD problem to further understand the well-known sloshing result. Next, the interaction between the ion inertial length, di, and the dynamically evolving current sheet scale length, (δJ), is established. Initially, diδJ. If η is such that (δJ) dynamically thins down to di prior to the well-known sloshing phenomena, then sloshing is avoided. This results in peak reconnection rates which are η-independent and scale as √di. However, if di is small enough that resistivity prevents (δJ) from thinning down to this scale prior to sloshing, then reconnection (and sloshing) proceeds as in the resistive MHD model. Finally, we discuss our development of a semi-analytical model to describe the well-known sloshing result in the resistive MHD model, and our plans to extend it to Hall MHD. D. A. Knoll, L. Chac'on, Phys. Plasmas, 13 (3), p.032307 (2006). D. A. Knoll, L. Chac'on, Phys. Rev. Lett., 96, 135001 (2006). A. Simakov, L. Chac'on, D. A. Knoll, Phys. Plasmas, accepted (2006).

BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia

PubMed Central

Zabriskie, Matthew S.; Eide, Christopher A.; Tantravahi, Srinivas K.; Vellore, Nadeem A.; Estrada, Johanna; Nicolini, Franck E.; Khoury, Hanna J.; Larson, Richard A.; Konopleva, Marina; Cortes, Jorge E.; Kantarjian, Hagop; Jabbour, Elias J.; Kornblau, Steven M.; Lipton, Jeffrey H.; Rea, Delphine; Stenke, Leif; Barbany, Gisela; Lange, Thoralf; Hernández-Boluda, Juan-Carlos; Ossenkoppele, Gert J.; Press, Richard D.; Chuah, Charles; Goldberg, Stuart L.; Wetzler, Meir; Mahon, Francois-Xavier; Etienne, Gabriel; Baccarani, Michele; Soverini, Simona; Rosti, Gianantonio; Rousselot, Philippe; Friedman, Ran; Deininger, Marie; Reynolds, Kimberly R.; Heaton, William L.; Eiring, Anna M.; Pomicter, Anthony D.; Khorashad, Jamshid S.; Kelley, Todd W.; Baron, Riccardo; Druker, Brian J.; Deininger, Michael W.; O'Hare, Thomas

2014-01-01

Summary Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1T315I mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome. PMID:25132497

Insecticide Resistance and Malaria Vector Control: The Importance of Fitness Cost Mechanisms in Determining Economically Optimal Control Trajectories

PubMed Central

Brown, Zachary S.; Dickinson, Katherine L.; Kramer, Randall A.

2014-01-01

The evolutionary dynamics of insecticide resistance in harmful arthropods has economic implications, not only for the control of agricultural pests (as has been well studied), but also for the control of disease vectors, such as malaria-transmitting Anopheles mosquitoes. Previous economic work on insecticide resistance illustrates the policy relevance of knowing whether insecticide resistance mutations involve fitness costs. Using a theoretical model, this article investigates economically optimal strategies for controlling malaria-transmitting mosquitoes when there is the potential for mosquitoes to evolve resistance to insecticides. Consistent with previous literature, we find that fitness costs are a key element in the computation of economically optimal resistance management strategies. Additionally, our models indicate that different biological mechanisms underlying these fitness costs (e.g., increased adult mortality and/or decreased fecundity) can significantly alter economically optimal resistance management strategies. PMID:23448053

Resonant and resistive dual-mode uncooled infrared detectors toward expanded dynamic range and high linearity

NASA Astrophysics Data System (ADS)

Li, Xin; Liang, Ji; Zhang, Hongxiang; Yang, Xing; Zhang, Hao; Pang, Wei; Zhang, Menglun

2017-06-01

This paper reports an uncooled infrared (IR) detector based on a micromachined piezoelectric resonator operating in resonant and resistive dual-modes. The two sensing modes achieved IR responsivities of 2.5 Hz/nW and 900 μdB/nW, respectively. Compared with the single mode operation, the dual-mode measurement improves the limit of detection by two orders of magnitude and meanwhile maintains high linearity and responsivity in a higher IR intensity range. A combination of the two sensing modes compensates for its own shortcomings and provides a much larger dynamic range, and thus, a wider application field of the proposed detector is realized.

Model task for the dynamics of an underwater two-legged walker

NASA Technical Reports Server (NTRS)

Beletskiy, V. V.; Golubkov, V. V.; Stepanova, Y. A.

1979-01-01

A model task of two-legged underwater walking was examined. Characteristics of the walking were established. The underwater walking device is a substantial sphere, which moves on dual-member legs. The dynamics of the device were investigated with the calculation of the buoyancy of Archimedes, and the force of hydrodynamic resistance.

Dynamic vapor sorption isotherms of medium grain rice varieties

USDA-ARS?s Scientific Manuscript database

It is known that the two popular medium rice varieties, namely M202 and M206, in California have different fissuring resistances. Therefore, the main goal of this study was to investigate the sorption behavior of these two varieties by a new approach using dynamic vapor sorption (DVS) method for elu...

Predation and bark beetle dynamics

Treesearch

John D. Reeve

1997-01-01

Bark beetle populations may undergo dramatic fluctuations and are often important pests in coniferous forests.Their dynamics are thought to be primarily driven by factors affecting the resistance of the host tree to attack, i.e., bottom-up forces, while natural enemies are usually assigned a minor role in these systems.I present behavioral experiments that suggest that...

Isolation of cultivation-resistant oomycetes, first detected as amplicon sequences, from roots of herbicide-terminated winter rye

USDA-ARS?s Scientific Manuscript database

The dynamics of microbial communities associated with dying cover crops are of interest because of potential impacts on disease in a subsequent crop, and because of the importance of microbial activity on plant residue to soil organic matter dynamics and nutrient cycling. High throughput amplicon se...

Madrean pine-oak forest in Arizona: past dynamics, present problems

Treesearch

Andrew M. Barton

2008-01-01

This paper synthesizes research on presettlement dynamics and modern disruption of Madrean pine-oak forests in Arizona. In response to surface fires characteristic of presettlement times, pines were fire resistant, exhibiting high top-survival, whereas oaks were fire resilient, exhibiting lower top-survival but pronounced resprouting. Thus, low-severity fire favors...

Phenotypic and genotypic characterisation of drug-resistant Plasmodium vivax

PubMed Central

Price, Ric N.; Auburn, Sarah; Marfurt, Jutta; Cheng, Qin

2015-01-01

In this review we present recent developments in the analysis of Plasmodium vivax clinical trials and ex vivo drug-susceptibility assays, as well approaches currently being used to identify molecular markers of drug resistance. Clinical trials incorporating the measurement of in vivo drug concentrations and parasite clearance times are needed to detect early signs of resistance. Analysis of P. vivax growth dynamics ex vivo have defined the criteria for acceptable assay thresholds for drug susceptibility testing, and their subsequent interpretation. Genotyping and next-generation sequencing studies in P. vivax field isolates are set to transform our understanding of the molecular mechanisms of drug resistance. PMID:23044287

Dynamic modulus of nanosilica modified porous asphalt

NASA Astrophysics Data System (ADS)

Arshad, A. K.; Masri, K. A.; Ahmad, J.; Samsudin, M. S.

2017-11-01

Porous asphalt (PA) is a flexible pavement layer with high interconnected air void contents and constructed using open-graded aggregates. Due to high temperature environment and increased traffic volume in Malaysia, PA may have deficiencies particularly in rutting and stiffness of the mix. A possible way to improve these deficiencies is to improve the asphalt binder used. Binder is normally modified using polymer materials to improve its properties. However, nanotechnology presently is being gradually used for asphalt modification. Nanosilica (NS), a byproduct of rice husk and palm oil fuel ash is used as additive in this study. The aim of this study is to enhance the rutting resistance and stiffness performance of PA using NS. This study focused on the performance of PA in terms of dynamic modulus with the addition of NS modified binder to produce better and more durable PA. From the result of Dynamic SPT Test, it shows that the addition of NS was capable in enhancing the stiffness and rutting resistance of PA. The addition of NS also increase the dynamic modulus value of PA by 50%.

Identification of spinal circuits involved in touch-evoked dynamic mechanical pain

PubMed Central

Cheng, Longzhen; Duan, Bo; Huang, Tianwen; Zhang, Yan; Chen, Yangyang; Britz, Olivier; Garcia-Campmany, Lidia; Ren, Xiangyu; Vong, Linh; Lowell, Bradford B.; Goulding, Martyn; Wang, Yun; Ma, Qiufu

2017-01-01

Mechanical hypersensitivity is a debilitating symptom associated with millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate. Here we report that dynamic mechanical hypersensitivity induced by nerve injury or inflammation was compromised in mice with ablation of spinal VT3Lbx1 neurons defined by coexpression of VGLUT3Cre and Lbx1Flpo, as indicated by the loss of brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. Meanwhile, the subset of somatostatin (SOM) lineage neurons preserved in VT3Lbx1 neuron-ablated mice is largely sufficient to mediate von Frey filament-evoked punctate mechanical hypersensitivity, including both morphine-sensitive and morphine-resistant forms. Furthermore, acute silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting these neurons as a potential cellular target for treating this form of neuropathic pain. PMID:28436981

A two-stage constitutive model of X12CrMoWVNbN10-1-1 steel during elevated temperature

NASA Astrophysics Data System (ADS)

Zhu, Luobei; He, Jianli; Zhang, Ying

2018-02-01

In order to clarify the competition between work hardening (WH) caused by dislocation movements and the dynamic softening result from dynamic recovery (DRV) and dynamic recrystallization (DRX), a new two-stage flow stress model of X12CrMoWVNbN10-1-1 (X12) ferrite heat-resistant steel was established to describe the whole hot deformation behavior. And the parameters were determined by the experimental data operated on a Gleeble-3800 thermo- mechanical simulation. In this constitutive model, a single internal variable dislocation density evolution model is used to describe the influence of WH and DRV to flow stress. The DRX kinetic dynamic model can express accurately the contribution of DRX to the decline of flow stress, which was established on the Avrami equation. Furthermore, The established new model was compared with Fields-Bachofen (F-B) model and experimental data. The results indicate the new two-stage flow stress model can more accurately represent the hot deformation behavior of X12 ferrite heat-resistant steel, and the average error is only 0.0995.

Fitness costs of resistance to antimalarial drugs.

PubMed

Felger, Ingrid; Beck, Hans-Peter

2008-08-01

It has been recently reported that the prevalence of mutations associated with chloroquine resistance declined during the dry season. Fitness costs of drug resistance were suggested to be responsible for reduced survival of mutant parasites, and only parasites surviving chronic infections were transmitted at the onset of the rainy season. This implies that during seasonal transmission, significant changes can occur in allele frequency over the course of months, rather than years. The practical consequences of these findings for monitoring dynamics of drug-resistance markers are: (i) in areas of seasonal transmission, the sampling date matters; (ii) fluctuations in mutation frequencies might be explained by seasonality; and (iii) a much-awaited experimental determination of fitness costs of drug resistance becomes within reach.

Simplifying the complexity of resistance heterogeneity in metastasis

PubMed Central

Lavi, Orit; Greene, James M.; Levy, Doron; Gottesman, Michael M.

2014-01-01

The main goal of treatment regimens for metastasis is to control growth rates, not eradicate all cancer cells. Mathematical models offer methodologies that incorporate high-throughput data with dynamic effects on net growth. The ideal approach would simplify, but not over-simplify, a complex problem into meaningful and manageable estimators that predict a patient’s response to specific treatments. Here, we explore three fundamental approaches with different assumptions concerning resistance mechanisms, in which the cells are categorized into either discrete compartments or described by a continuous range of resistance levels. We argue in favor of modeling resistance as a continuum and demonstrate how integrating cellular growth rates, density-dependent versus exponential growth, and intratumoral heterogeneity improves predictions concerning the resistance heterogeneity of metastases. PMID:24491979

The Dynamics of Drug Resistance: A Mathematical Perspective

PubMed Central

Lavi, Orit; Gottesman, Michael M.; Levy, Doron

2012-01-01

Resistance to chemotherapy is a key impediment to successful cancer treatment that has been intensively studied for the last three decades. Several central mechanisms have been identified as contributing to the resistance. In the case of multidrug resistance (MDR), the cell becomes resistant to a variety of structurally and mechanistically unrelated drugs in addition to the drug initially administered. Mathematical models of drug resistance have dealt with many of the known aspects of this field, such as pharmacologic sanctuary and location/diffusion resistance, intrinsic resistance that is therapy independent, therapy-dependent cellular alterations including induced resistance (dose-dependent) and acquired resistance (dose-independent). In addition, there are mathematical models that take into account the kinetic/phase resistance, and models that investigate intra-cellular mechanisms based on specific biological functions (such as ABC transporters, apoptosis and repair mechanisms). This review covers aspects of MDR that have been mathematically studied, and explains how, from a methodological perspective, mathematics can be used to study drug resistance. We discuss quantitative approaches of mathematical analysis, and demonstrate how mathematics can be used in combination with other experimental and clinical tools. We emphasize the potential benefits of integrating analytical and mathematical methods into future clinical and experimental studies of drug resistance. PMID:22387162

Markers linked to wheat stem rust resistance gene Sr11 effective to Puccinia graminis f. sp. tritici race TKTTF

USDA-ARS?s Scientific Manuscript database

Wheat stem rust caused by Puccinia graminis f. sp. tritici can cause severe yield losses on susceptible wheat varieties and cultivars. Although stem rust can be controlled by the use of genetic resistance, population dynamics of P. graminis f. sp. tritici can frequently lead to defeat of wheat stem ...

Experimental research on microhardness and wear resistances of pure Cu subjected to surface dynamic plastic deformation by ultrasonic impact

NASA Astrophysics Data System (ADS)

Chen, Zhaoxia; He, Yangming

2018-04-01

Dynamic plastic deformation (DPD) has been induced in the surface of pure Cu by ultrasonic impact treating (UIT) with the varied impact current and coverage percentage. The microstructures of the treated surface were analyzed by a scanning electron microscope (SEM). And the wear resistance of pure Cu was experimentally researched both with the treated and untreated specimens. The effect of DPD on the hardness was also investigated using microhardness tester. The results show that the grains on the top surfaces of pure Cu are highly refined. The maximum depth of the plastic deformation layer is approximately 1400 µm. The larger the current and coverage percentage, the greater of the microhardness and wear resistance the treated surface layer of pure Cu will be. When the impact current is 2 A and coverage percentage is 300%, the microhardness and wear resistance of the treated sample is about 276.1% and 68.8% higher than that of the untreated specimen, respectively. But the properties of the treated sample deteriorate when the UIT current is 3 A and the coverage percentage is 300% because of the formation of a new phase forms in the treated surface.

The spatiotemporal system dynamics of acquired resistance in an engineered microecology.

PubMed

Datla, Udaya Sree; Mather, William H; Chen, Sheng; Shoultz, Isaac W; Täuber, Uwe C; Jones, Caroline N; Butzin, Nicholas C

2017-11-22

Great strides have been made in the understanding of complex networks; however, our understanding of natural microecologies is limited. Modelling of complex natural ecological systems has allowed for new findings, but these models typically ignore the constant evolution of species. Due to the complexity of natural systems, unanticipated interactions may lead to erroneous conclusions concerning the role of specific molecular components. To address this, we use a synthetic system to understand the spatiotemporal dynamics of growth and to study acquired resistance in vivo. Our system differs from earlier synthetic systems in that it focuses on the evolution of a microecology from a killer-prey relationship to coexistence using two different non-motile Escherichia coli strains. Using empirical data, we developed the first ecological model emphasising the concept of the constant evolution of species, where the survival of the prey species is dependent on location (distance from the killer) or the evolution of resistance. Our simple model, when expanded to complex microecological association studies under varied spatial and nutrient backgrounds may help to understand the complex relationships between multiple species in intricate natural ecological networks. This type of microecological study has become increasingly important, especially with the emergence of antibiotic-resistant pathogens.

Uniting Gradual and Abrupt set Processes in Resistive Switching Oxides

NASA Astrophysics Data System (ADS)

Fleck, Karsten; La Torre, Camilla; Aslam, Nabeel; Hoffmann-Eifert, Susanne; Böttger, Ulrich; Menzel, Stephan

2016-12-01

Identifying limiting factors is crucial for a better understanding of the dynamics of the resistive switching phenomenon in transition-metal oxides. This improved understanding is important for the design of fast-switching, energy-efficient, and long-term stable redox-based resistive random-access memory devices. Therefore, this work presents a detailed study of the set kinetics of valence change resistive switches on a time scale from 10 ns to 104 s , taking Pt /SrTiO3/TiN nanocrossbars as a model material. The analysis of the transient currents reveals that the switching process can be subdivided into a linear-degradation process that is followed by a thermal runaway. The comparison with a dynamical electrothermal model of the memory cell allows the deduction of the physical origin of the degradation. The origin is an electric-field-induced increase of the oxygen-vacancy concentration near the Schottky barrier of the Pt /SrTiO3 interface that is accompanied by a steadily rising local temperature due to Joule heating. The positive feedback of the temperature increase on the oxygen-vacancy mobility, and thereby on the conductivity of the filament, leads to a self-acceleration of the set process.

Single Active Site Mutation Causes Serious Resistance of HIV Reverse Transcriptase to Lamivudine: Insight from Multiple Molecular Dynamics Simulations.

PubMed

Moonsamy, Suri; Bhakat, Soumendranath; Walker, Ross C; Soliman, Mahmoud E S

2016-03-01

Molecular dynamics simulations, binding free energy calculations, principle component analysis (PCA), and residue interaction network analysis were employed in order to investigate the molecular mechanism of M184I single mutation which played pivotal role in making the HIV-1 reverse transcriptase (RT) totally resistant to lamivudine. Results showed that single mutations at residue 184 of RT caused (1) distortion of the orientation of lamivudine in the active site due to the steric conflict between the oxathiolane ring of lamivudine and the side chain of beta-branched amino acids Ile at position 184 which, in turn, perturbs inhibitor binding, (2) decrease in the binding affinity by (~8 kcal/mol) when compared to the wild-type, (3) variation in the overall enzyme motion as evident from the PCA for both systems, and (4) distortion of the hydrogen bonding network and atomic interactions with the inhibitor. The comprehensive analysis presented in this report can provide useful information for understanding the drug resistance mechanism against lamivudine. The results can also provide some potential clues for further design of novel inhibitors that are less susceptible to drug resistance.

Modeling the Population Dynamics of Antibiotic-Resistant Bacteria:. AN Agent-Based Approach

NASA Astrophysics Data System (ADS)

Murphy, James T.; Walshe, Ray; Devocelle, Marc

The response of bacterial populations to antibiotic treatment is often a function of a diverse range of interacting factors. In order to develop strategies to minimize the spread of antibiotic resistance in pathogenic bacteria, a sound theoretical understanding of the systems of interactions taking place within a colony must be developed. The agent-based approach to modeling bacterial populations is a useful tool for relating data obtained at the molecular and cellular level with the overall population dynamics. Here we demonstrate an agent-based model, called Micro-Gen, which has been developed to simulate the growth and development of bacterial colonies in culture. The model also incorporates biochemical rules and parameters describing the kinetic interactions of bacterial cells with antibiotic molecules. Simulations were carried out to replicate the development of methicillin-resistant S. aureus (MRSA) colonies growing in the presence of antibiotics. The model was explored to see how the properties of the system emerge from the interactions of the individual bacterial agents in order to achieve a better mechanistic understanding of the population dynamics taking place. Micro-Gen provides a good theoretical framework for investigating the effects of local environmental conditions and cellular properties on the response of bacterial populations to antibiotic exposure in the context of a simulated environment.

Pathogen dynamics during invasion and establishment of white-nose syndrome explain mechanisms of host persistence.

PubMed

Frick, Winifred F; Cheng, Tina L; Langwig, Kate E; Hoyt, Joseph R; Janicki, Amanda F; Parise, Katy L; Foster, Jeffrey T; Kilpatrick, A Marm

2017-03-01

Disease dynamics during pathogen invasion and establishment determine the impacts of disease on host populations and determine the mechanisms of host persistence. Temporal progression of prevalence and infection intensity illustrate whether tolerance, resistance, reduced transmission, or demographic compensation allow initially declining populations to persist. We measured infection dynamics of the fungal pathogen Pseudogymnoascus destructans that causes white-nose syndrome in bats by estimating pathogen prevalence and load in seven bat species at 167 hibernacula over a decade as the pathogen invaded, became established, and some host populations stabilized. Fungal loads increased rapidly and prevalence rose to nearly 100% at most sites within 2 yr of invasion in six of seven species. Prevalence and loads did not decline over time despite huge reductions in colony sizes, likely due to an extensive environmental reservoir. However, there was substantial variation in fungal load among sites with persisting colonies, suggesting that both tolerance and resistance developed at different sites in the same species. In contrast, one species disappeared from hibernacula within 3 yr of pathogen invasion. Variable host responses to pathogen invasion require different management strategies to prevent disease-induced extinction and to facilitate evolution of tolerance or resistance in persisting populations. © 2016 by the Ecological Society of America.

Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses.

PubMed

Lagator, Mato; Colegrave, Nick; Neve, Paul

2014-11-07

In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

SDVSRM - a new SSRM based technique featuring dynamically adjusted, scanner synchronized sample voltages for measurement of actively operated devices.

PubMed

Doering, Stefan; Wachowiak, Andre; Roetz, Hagen; Eckl, Stefan; Mikolajick, Thomas

2018-06-01

Scanning spreading resistance microscopy (SSRM) with its high spatial resolution and high dynamic signal range is a powerful tool for two-dimensional characterization of semiconductor dopant areas. However, the application of the method is limited to devices in equilibrium condition, as the investigation of actively operated devices would imply potential differences within the device, whereas SSRM relies on a constant voltage difference between sample surface and probe tip. Furthermore, the standard preparation includes short circuiting of all device components, limiting applications to devices in equilibrium condition. In this work scanning dynamic voltage spreading resistance microscopy (SDVSRM), a new SSRM based two pass atomic force microscopy (AFM) technique is introduced, overcoming these limitations. Instead of short circuiting the samples during preparation, wire bond devices are used allowing for active control of the individual device components. SDVSRM consists of two passes. In the first pass the local sample surface voltage dependent on the dc biases applied to the components of the actively driven device is measured as in scanning voltage microscopy (SVM). The local spreading resistance is measured within the second pass, in which the afore obtained local surface voltage is used to dynamically adjust the terminal voltages of the device under test. This is done in a way that the local potential difference across the nano-electrical contact matches the software set SSRM measurement voltage, and at the same time, the internal voltage differences within the device under test are maintained. In this work the proof of the concept could be demonstrated by obtaining spreading resistance data of an actively driven photodiode test device. SDVSRM adds a higher level of flexibility in general to SSRM, as occurring differences in cross section surface voltage are taken into account. These differences are immanent for actively driven devices, but can also be present at standard, short circuited samples. Therefore, SDVSRM could improve the characterization under equilibrium conditions as well. Copyright © 2018. Published by Elsevier B.V.

Evolution of Resistance to Targeted Anti-Cancer Therapies during Continuous and Pulsed Administration Strategies

PubMed Central

Foo, Jasmine; Michor, Franziska

2009-01-01

The discovery of small molecules targeted to specific oncogenic pathways has revolutionized anti-cancer therapy. However, such therapy often fails due to the evolution of acquired resistance. One long-standing question in clinical cancer research is the identification of optimum therapeutic administration strategies so that the risk of resistance is minimized. In this paper, we investigate optimal drug dosing schedules to prevent, or at least delay, the emergence of resistance. We design and analyze a stochastic mathematical model describing the evolutionary dynamics of a tumor cell population during therapy. We consider drug resistance emerging due to a single (epi)genetic alteration and calculate the probability of resistance arising during specific dosing strategies. We then optimize treatment protocols such that the risk of resistance is minimal while considering drug toxicity and side effects as constraints. Our methodology can be used to identify optimum drug administration schedules to avoid resistance conferred by one (epi)genetic alteration for any cancer and treatment type. PMID:19893626

Origin of resistivity in reconnection

NASA Astrophysics Data System (ADS)

Treumann, Rudolf A.

2001-06-01

Resistivity is believed to play an important role in reconnection leading to the distinction between resistive and collisionless reconnection. The former is treated in the Sweet-Parker model of long current sheets, and the Petschek model of a small resistive region. Both models in spite of their different dynamics attribute to the violation of the frozen-in condition in their diffusion regions due to the action of resistivity. In collisionless reconnection there is little consensus about the processes breaking the frozen-in condition. The question is whether anomalous processes generate sufficient resistivity or whether other processes free the particles from slavery by the magnetic field. In the present paper we review processes that may cause anomalous resistivity in collisionless current sheets. Our general conclusion is that in space plasma boundaries accessible to in situ spacecraft, wave levels have always been found to be high enough to explain the existence of large enough local diffusivity for igniting local reconnection. However, other processes might take place as well. Non-resistive reconnection can be caused by inertia or diamagnetism.

Dynamic moisture sorption characteristics of enzyme-resistant recrystallized cassava starch.

PubMed

Mutungi, Christopher; Schuldt, Stefan; Onyango, Calvin; Schneider, Yvonne; Jaros, Doris; Rohm, Harald

2011-03-14

The interaction of moisture with enzyme-resistant recrystallized starch, prepared by heat-moisture treatment of debranched acid-modified or debranched non-acid-modified cassava starch, was investigated in comparison with the native granules. Crystallinities of the powdered products were estimated by X-ray diffraction. Moisture sorption was determined using dynamic vapor sorption analyzer and data fitted to various models. Percent crystallinities of native starch (NS), non-acid-modified recrystallized starch (NAMRS), and acid-modified recrystallized starch (AMRS) were 39.7, 51.9, and 56.1%, respectively. In a(w) below 0.8, sorption decreased in the order NS > NAMRS > AMRS in line with increasing sample crystallinities but did not follow this crystallinity dependence at higher a(w) because of condensation and polymer dissolution effects. Adsorbed moisture became internally absorbed in NS but not in NAMRS and AMRS, which might explain the high resistance of the recrystallized starches to digestion because enzyme and starch cannot approach each other over fairly sufficient surface at the molecular level.

Shape optimization of an autonomous underwater vehicle with a ducted propeller using computational fluid dynamics analysis

NASA Astrophysics Data System (ADS)

Joung, Tae-Hwan; Sammut, Karl; He, Fangpo; Lee, Seung-Keon

2012-03-01

Autonomous Underwater Vehicles (AUVs) provide a useful means of collecting detailed oceano-graphic information. The hull resistance of an AUV is an important factor in determining the power requirements and range of the vehicle. This paper describes a procedure using Computational Fluid Dynamics (CFD) for determining the hull resistance of an AUV under development, for a given propeller rotation speed and within a given range of AUV velocities. The CFD analysis results reveal the distribution of the hydrodynamic values (velocity, pressure, etc.) around the AUV hull and its ducted propeller. The paper then proceeds to present a methodology for optimizing the AUV profile in order to reduce the total resistance. This paper demonstrates that shape optimization of conceptual designs is possible using the commercial CFD package contained in Ansys™. The optimum design to minimize the drag force of the AUV was identified for a given object function and a set of constrained design parameters

Single cell model for simultaneous drug delivery and efflux.

PubMed

Yi, C; Saidel, G M; Gratzl, M

1999-01-01

Multidrug resistance (MDR) of some cancer cells is a major challenge for chemotherapy of systemic cancers to overcome. To experimentally uncover the cellular mechanisms leading to MDR, it is necessary to quantitatively assess both drug influx into, and efflux from, the cells exposed to drug treatment. By using a novel molecular microdelivery system to enforce continuous and adjustable drug influx into single cells by controlled diffusion through a gel plug in a micropipet tip, drug resistance studies can now be performed on the single cell level. Our dynamic model of this scheme incorporates drug delivery, diffusive mixing, and accumulation inside the cytoplasm, and efflux by both passive and active membrane transport. Model simulations using available experimental information on these processes can assist in the design of MDR related experiments on single cancer cells which are expected to lead to a quantitative evaluation of mechanisms. Simulations indicate that drug resistance of a cancer cell can be quantified better by its dynamic response than by steady-state analysis.

Space shuttle prototype check valve development

NASA Technical Reports Server (NTRS)

Tellier, G. F.

1976-01-01

Contaminant-resistant seal designs and a dynamically stable prototype check valve for the orbital maneuvering and reaction control helium pressurization systems of the space shuttle were developed. Polymer and carbide seal models were designed and tested. Perfluoroelastomers compatible with N2O4 and N2H4 types were evaluated and compared with Teflon in flat and captive seal models. Low load sealing and contamination resistance tests demonstrated cutter seal superiority over polymer seals. Ceramic and carbide materials were evaluated for N2O4 service using exposure to RFNA as a worst case screen; chemically vapor deposited tungsten carbide was shown to be impervious to the acid after 6 months immersion. A unique carbide shell poppet/cutter seat check valve was designed and tested to demonstrate low cracking pressure ( 2.0 psid), dynamic stability under all test bench flow conditions, contamination resistance (0.001 inch CRES wires cut with 1.5 pound seat load) and long life of 100,000 cycles (leakage 1.0 scc/hr helium from 0.1 to 400 psig).

Tutorial: Determination of thermal boundary resistance by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Liang, Zhi; Hu, Ming

2018-05-01

Due to the high surface-to-volume ratio of nanostructured components in microelectronics and other advanced devices, the thermal resistance at material interfaces can strongly affect the overall thermal behavior in these devices. Therefore, the thermal boundary resistance, R, must be taken into account in the thermal analysis of nanoscale structures and devices. This article is a tutorial on the determination of R and the analysis of interfacial thermal transport via molecular dynamics (MD) simulations. In addition to reviewing the commonly used equilibrium and non-equilibrium MD models for the determination of R, we also discuss several MD simulation methods which can be used to understand interfacial thermal transport behavior. To illustrate how these MD models work for various interfaces, we will show several examples of MD simulation results on thermal transport across solid-solid, solid-liquid, and solid-gas interfaces. The advantages and drawbacks of a few other MD models such as approach-to-equilibrium MD and first-principles MD are also discussed.

Oxidation-Resistant Surfaces For Solar Reflectors

NASA Technical Reports Server (NTRS)

Gulino, Daniel A.; Egger, Robert A.; Banholzer, William F.

1988-01-01

Thin films on silver provide highly-reflective, corrosion-resistant mirrors. Study evaluated variety of oxidation-resistant reflective materials for use in solar dynamic power system, one that generates electricity by focusing Sunlight onto reciever of heat engine. Thin films of platinum and rhodium deposited by ion-beam sputtering on various substrate materials. Solar reflectances measured as function of time of exposure to radio-frequency-generated air plasma. Several protective coating materials deposited on silver-coated substrates and exposed to plasma. Analyzed before and after exposure by electon spectroscopy for chemical analysis and by Auger spectroscopy.

Decomposition of the Thermal Boundary Resistance across Carbon Nanotube-Graphene Junctions to Different Mechanisms.

PubMed

Shi, Jingjing; Zhong, Yang; Fisher, Timothy S; Ruan, Xiulin

2018-05-02

Three different mechanisms are identified to contribute to thermal resistances across a carbon nanotube-graphene junction: material mismatch, nonplanar junction, and defects. To isolate the contributions of each mechanism, we have designed five types of junctions and performed nonequilibrium molecular dynamics simulations. The results show that the contributions from the three mechanisms are similar, each at around 2.5 × 10 -11 m 2 K/W. The relations between thermal boundary resistance and both defect number and turning angle at the interface are also studied.

Flow dynamics in pediatric rigid bronchoscopes using computer-aided design modeling software.

PubMed

Barneck, Mitchell D; Webb, J Taylor; Robinson, Ryan E; Grimmer, J Fredrik

2016-08-01

Observed complications during rigid bronchoscopy, including hypercarbia and hypoxemia, prompted us to assess how well rigid bronchoscopes serve as an airway device. We performed computer-aided design flow analysis of pediatric rigid bronchoscopes to gain insight into flow dynamics. We made accurate three-dimensional computer models of pediatric rigid bronchoscopes and endotracheal tubes. SOLIDWORKS (Dassault Systemes, Vélizy-Villacoublay, France) flow analysis software was used to analyze fluid dynamics during pressure-controlled and volume-controlled ventilation. Flow analysis was performed on rigid bronchoscopes and similar outer diameter endotracheal tubes comparing resistance, flow, and turbulence during two ventilation modalities and in common surgical scenarios. Increased turbulent flow was observed in bronchoscopes compared to more laminar flow in endotracheal tubes of similar outer diameter. Flow analysis displayed higher resistances in all pediatric bronchoscope sizes except one (3.0 bronchoscope) compared to similar-sized endotracheal tubes. Loss of adequate ventilation was observed if the bronchoscope was not assembled correctly or if increased peak inspiratory pressures were needed. Anesthesia flow to the patient was reduced by 63% during telescope insertion. Flow analysis illustrates increased turbulent flow and increased airflow resistance in all but one size of pediatric bronchoscopes compared to endotracheal tubes. This increased turbulence and resistance, along with the unanticipated gas distal exit pattern, may contribute to the documented hypercarbia and hypoxemia during procedures. These findings may explain why hypoxemia and hypercarbia are commonly observed during rigid bronchoscopy, especially when positive pressure ventilation is needed. NA Laryngoscope, 126:1940-1945, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Influence of resistance load on neuromuscular response to vibration training.

PubMed

Luo, Jin; Clarke, Michael; McNamara, Brian; Moran, Kieran

2009-03-01

The purpose of this study was to examine the influence of resistance load on the acute and acute residual effects of vibration training, with vibration applied directly to the bicep tendon in a maximal-effort dynamic resistance exercise (3 sets of maximal-effort bicep curls). Eleven participants were exposed to 4 training conditions in random order: exercise with 1 of 2 different loads (40% 1-repetition maximum [RM] or 70% 1RM load) combined with 1 of 2 vibration conditions (vibration [1.2 mm, 65 Hz] or sham vibration). Five minutes before and after the exercise, a set of maximal-effort bicep curls with a load of either 40 or 70% 1RM was performed as the pre- and posttraining test. Concentric elbow joint angular velocity, moment and power, and bicep root mean square electromyography (EMGrms) were measured during training and in the pre- and posttraining tests. The results show that during training (acute effect) and at 5 minutes after training (acute residual effect), vibration did not induce a significant change in EMGrms, mean and peak angular velocities, moment and power, time to peak power, and initial power at 100 milliseconds after the start of the concentric phase for either resistance load. Therefore, in aiming to train neuromuscular output using maximal-effort dynamic contractions (40 and 70% 1RM), there is no benefit in employing direct vibration, at least with a 1.2-mm amplitude and 65-Hz frequency. However, the amplitude of 1.2 mm may be too high to effectively stimulate neuromuscular output in maximal-effort dynamic contractions per se.

Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment.

PubMed

Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo; Græsbøll, Kaare; Toft, Nils; Matthews, Louise; Nielsen, Søren Saxmose; Olsen, John Elmerdahl

2016-09-06

This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains in the intestine of nursery pigs. It also examined the dynamics of the composition of bacterial strains during and after the treatment. The growth responses of strains to ampicillin concentrations were determined using in vitro growth curves. Using these results as input data, growth predictions were generated using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most susceptible strains were more affected by increasing concentrations of antibiotics that the rest of the strains. The modeling revealed that short treatment duration resulted in lower levels of resistance and that dosing frequency did not substantially influence the growth of resistant strains. Resistance levels were found to be sensitive to the number of competing strains, and this effect was enhanced by longer duration of treatment. High excretion of bacteria from the intestine favored resistant strains over sensitive strains, but at the same time it resulted in a faster return to pre-treatment levels after the treatment ended. When the duration of high excretion was set to be limited to the treatment time (i.e. the treatment was assumed to result in a cure of diarrhea) resistant strains required longer time to reach the previous level. No fitness cost was found to be associated with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in relation to optimal treatment strategies. The modeling approach used in the study is generic, and could be used for prediction of the effect of treatment with other drugs and other administration routes for effect on resistance development in the intestine of pigs.

Dynamic strain aging in the high-temperature low-cycle fatigue of SA508 Cl. 3 forging steel

NASA Astrophysics Data System (ADS)

Lee, Byung Ho; Kim, In Sup

1995-10-01

The effect of dynamic strain aging on cyclic stress response and fatigue resistance of ASME SA508 Cl.3 forging steel for nuclear reactor pressure vessels has been evaluated in the temperature range of room temperature to 500°C. Total strain ranges and strain rates were varied from 0.7 to 2.0% and from 4 × 10 -4 to 1 × 10 -2 s -1, respectively. The cyclic stress response depended on the testing temperature, strain rate, and range. Generally, the initial cyclic hardening was immediately followed by cyclic softening at all strain rates. However, at 300°C, the operating temperature of nuclear reactor pressure vessels, the variation of cyclic stress amplitude showed the primary and secondary hardening stages dependent on the strain rate and strain range. Dynamic strain aging was manifested by enhanced cyclic hardening, distinguished secondary hardening, and negative strain rate sensitivity. A modified cell shutting model was described for the onset of the secondary hardening due to the dynamic strain aging and it was in good agreement with the experimental results. Fatigue life increased in strain rate at all testing temperatures. Specifically the fatigue life was longer at the dynamic strain aging temperature. Further, the dynamic strain aging was easy to initiate the crack, while crack propagation was retarded by crack branching and suppression of plastic zone, hence the dynamic strain aging caused the improvement of fatigue resistance.

Muscle function in aged women in response to a water-based exercises program and progressive resistance training.

PubMed

Bento, Paulo Cesar Barauce; Rodacki, André Luiz Felix

2015-11-01

The purpose of the present study was to determine the effects of a water-based exercise program on muscle function compared with regular high-intensity resistance training. Older women (n = 87) were recruited from the local community. The inclusion criteria were, to be aged 60 years or older, able to walk and able to carry out daily living activities independently. Participants were randomly assigned to one of the following groups: water-based exercises (WBG), resistance training (RTG) or control (CG). The experimental groups carried out 12 weeks of an excise program performed on water or on land. The dynamic strength, the isometric peak, and rate of torque development for the lower limbs were assessed before and after interventions. The water-based program provided a similar improvement in dynamic strength in comparison with resistance training. The isometric peak torque increased around the hip and ankle joints in the water-based group, and around the knee joint in the resistance-training group (P < 0.05). The rate of torque development increased only in the water-based group around the hip extensors muscles (P < 0.05). Water-based programs constitute an attractive alternative to promote relevant strength gains using moderate loads and fast speed movements, which were also effective to improve the capacity to generate fast torques. © 2014 Japan Geriatrics Society.

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila.

PubMed

Descours, Ghislaine; Ginevra, Christophe; Jacotin, Nathalie; Forey, Françoise; Chastang, Joëlle; Kay, Elisabeth; Etienne, Jerome; Lina, Gérard; Doublet, Patricia; Jarraud, Sophie

2017-03-01

Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy, but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila Twelve independent lineages from a common susceptible L. pneumophila ancestral strain were propagated under conditions of erythromycin or azithromycin pressure to produce high-level macrolide resistance. Whole-genome sequencing was performed on 12 selected clones, and we investigated mutations common to all lineages. We reconstructed the dynamics of mutation for each lineage and demonstrated their involvement in decreased susceptibility to macrolides. The resistant mutants were produced in a limited number of passages to obtain a 4,096-fold increase in erythromycin MICs. Mutations affected highly conserved 5-amino-acid regions of L4 and L22 ribosomal proteins and of domain V of 23S rRNA (G2057, A2058, A2059, and C2611 nucleotides). The early mechanisms mainly affected L4 and L22 proteins and induced a 32-fold increase in the MICs of the selector drug. Additional mutations related to 23S rRNA mostly occurred later and were responsible for a major increase of macrolide MICs, depending on the mutated nucleotide, the substitution, and the number of mutated genes among the three rrl copies. The major mechanisms of the decreased susceptibility to macrolides in L. pneumophila and their dynamics were determined. The results showed that macrolide resistance could be easily selected in L. pneumophila and warrant further investigations in both clinical and environmental settings. Copyright © 2017 American Society for Microbiology.

Dynamic Fatigue of a Titanium Silicate Glass

NASA Technical Reports Server (NTRS)

Tucker, Dennis S.; Nettles, Alan T.; Cagle, Holly A.; Smith, W. Scott (Technical Monitor)

2002-01-01

A dynamic fatigue study was performed on a Titanium Silicate Glass in order to assess its susceptibility to delayed failure. Fracture mechanics techniques were used to analyze the results for the purpose of making lifetime predictions for optical elements made from this material. The material has reasonably good resistance (N=23 to stress corrosion in ambient conditions).

What you feel is what you see: inverse dynamics estimation underlies the resistive sensation of a delayed cursor

PubMed Central

Takamuku, Shinya; Gomi, Hiroaki

2015-01-01

How our central nervous system (CNS) learns and exploits relationships between force and motion is a fundamental issue in computational neuroscience. While several lines of evidence have suggested that the CNS predicts motion states and signals from motor commands for control and perception (forward dynamics), it remains controversial whether it also performs the ‘inverse’ computation, i.e. the estimation of force from motion (inverse dynamics). Here, we show that the resistive sensation we experience while moving a delayed cursor, perceived purely from the change in visual motion, provides evidence of the inverse computation. To clearly specify the computational process underlying the sensation, we systematically varied the visual feedback and examined its effect on the strength of the sensation. In contrast to the prevailing theory that sensory prediction errors modulate our perception, the sensation did not correlate with errors in cursor motion due to the delay. Instead, it correlated with the amount of exposure to the forward acceleration of the cursor. This indicates that the delayed cursor is interpreted as a mechanical load, and the sensation represents its visually implied reaction force. Namely, the CNS automatically computes inverse dynamics, using visually detected motions, to monitor the dynamic forces involved in our actions. PMID:26156766

Evaluation of Permanent Deformation of CRM-Reinforced SMA and Its Correlation with Dynamic Stiffness and Dynamic Creep

PubMed Central

Mashaan, Nuha Salim; Karim, Mohamed Rehan

2013-01-01

Today, rapid economic and industrial growth generates increasing amounts of waste materials such as waste tyre rubber. Attempts to inspire a green technology which is more environmentally friendly that can produce economic value are a major consideration in the utilization of waste materials. The aim of this study is to evaluate the effect of waste tyre rubber (crumb rubber modifier (CRM)), in stone mastic asphalt (SMA 20) performance. The virgin bitumen (80/100) penetration grade was used, modified with crumb rubber at four different modification levels, namely, 6%, 12%, 16%, and 20% by weight of the bitumen. The testing undertaken on the asphalt mix comprises the indirect tensile (dynamic stiffness), dynamic creep, and wheel tracking tests. By the experimentation, the appropriate amount of CRM was found to be 16% by weight of bitumen. The results show that the addition of CRM into the mixture has an obvious significant effect on the performance properties of SMA which could improve the mixture's resistance against permanent deformation. Further, higher correlation coefficient was obtained between the rut depth and permanent strain as compared to resilient modulus; thus dynamic creep test might be a more reliable test in evaluating the rut resistance of asphalt mixture. PMID:24302883

Evaluation of permanent deformation of CRM-reinforced SMA and its correlation with dynamic stiffness and dynamic creep.

PubMed

Mashaan, Nuha Salim; Karim, Mohamed Rehan

2013-01-01

Today, rapid economic and industrial growth generates increasing amounts of waste materials such as waste tyre rubber. Attempts to inspire a green technology which is more environmentally friendly that can produce economic value are a major consideration in the utilization of waste materials. The aim of this study is to evaluate the effect of waste tyre rubber (crumb rubber modifier (CRM)), in stone mastic asphalt (SMA 20) performance. The virgin bitumen (80/100) penetration grade was used, modified with crumb rubber at four different modification levels, namely, 6%, 12%, 16%, and 20% by weight of the bitumen. The testing undertaken on the asphalt mix comprises the indirect tensile (dynamic stiffness), dynamic creep, and wheel tracking tests. By the experimentation, the appropriate amount of CRM was found to be 16% by weight of bitumen. The results show that the addition of CRM into the mixture has an obvious significant effect on the performance properties of SMA which could improve the mixture's resistance against permanent deformation. Further, higher correlation coefficient was obtained between the rut depth and permanent strain as compared to resilient modulus; thus dynamic creep test might be a more reliable test in evaluating the rut resistance of asphalt mixture.

In-vitro development of a temporal abutment screw to protect osseointegration in immediate loaded implants.

PubMed

García-Roncero, Herminio; Caballé-Serrano, Jordi; Cano-Batalla, Jordi; Cabratosa-Termes, Josep; Figueras-Álvarez, Oscar

2015-04-01

In this study, a temporal abutment fixation screw, designed to fracture in a controlled way upon application of an occlusal force sufficient to produce critical micromotion was developed. The purpose of the screw was to protect the osseointegration of immediate loaded single implants. Seven different screw prototypes were examined by fixing titanium abutments to 112 Mozo-Grau external hexagon implants (MG Osseous®; Mozo-Grau, S.A., Valladolid, Spain). Fracture strength was tested at 30° in two subgroups per screw: one under dynamic loading and the other without prior dynamic loading. Dynamic loading was performed in a single-axis chewing simulator using 150,000 load cycles at 50 N. After normal distribution of obtained data was verified by Kolmogorov-Smirnov test, fracture resistance between samples submitted and not submitted to dynamic loading was compared by the use of Student's t-test. Comparison of fracture resistance among different screw designs was performed by the use of one-way analysis of variance. Confidence interval was set at 95%. Fractures occurred in all screws, allowing easy retrieval. Screw Prototypes 2, 5 and 6 failed during dynamic loading and exhibited statistically significant differences from the other prototypes. Prototypes 2, 5 and 6 may offer a useful protective mechanism during occlusal overload in immediate loaded implants.

Regulation of mitochondrial bioenergetics by the non-canonical roles of mitochondrial dynamics proteins in the heart.

PubMed

Wang, Wang; Fernandez-Sanz, Celia; Sheu, Shey-Shing

2018-05-01

Recent advancement in mitochondrial research has significantly extended our knowledge on the role and regulation of mitochondria in health and disease. One important breakthrough is the delineation of how mitochondrial morphological changes, termed mitochondrial dynamics, are coupled to the bioenergetics and signaling functions of mitochondria. In general, it is believed that fusion leads to an increased mitochondrial respiration efficiency and resistance to stress-induced dysfunction while fission does the contrary. This concept seems not applicable to adult cardiomyocytes. The mitochondria in adult cardiomyocytes exhibit fragmented morphology (tilted towards fission) and show less networking and movement as compared to other cell types. However, being the most energy-demanding cells, cardiomyocytes in the adult heart possess vast number of mitochondria, high level of energy flow, and abundant mitochondrial dynamics proteins. This apparent discrepancy could be explained by recently identified new functions of the mitochondrial dynamics proteins. These "non-canonical" roles of mitochondrial dynamics proteins range from controlling inter-organelle communication to regulating cell viability and survival under metabolic stresses. Here, we summarize the newly identified non-canonical roles of mitochondrial dynamics proteins. We focus on how these fission and fusion independent roles of dynamics proteins regulate mitochondrial bioenergetics. We also discuss potential molecular mechanisms, unique intracellular location, and the cardiovascular disease relevance of these non-canonical roles of the dynamics proteins. We propose that future studies are warranted to differentiate the canonical and non-canonical roles of dynamics proteins and to identify new approaches for the treatment of heart diseases. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers. Copyright © 2017 Elsevier B.V. All rights reserved.

Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes

DOE PAGES

Travers, Timothy; Wang, Katherine J.; Lopez, Cesar A.; ...

2018-02-09

Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this paper, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes

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

Travers, Timothy; Wang, Katherine J.; Lopez, Cesar A.

Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this paper, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

HIV Genetic Diversity and Drug Resistance.

PubMed

Santos, André F; Soares, Marcelo A

2010-02-01

Most of the current knowledge on antiretroviral (ARV) drug development and resistance is based on the study of subtype B of HIV-1, which only accounts for 10% of the worldwide HIV infections. Cumulative evidence has emerged that different HIV types, groups and subtypes harbor distinct biological properties, including the response and susceptibility to ARV. Recent laboratory and clinical data highlighting such disparities are summarized in this review. Variations in drug susceptibility, in the emergence and selection of specific drug resistance mutations, in viral replicative capacity and in the dynamics of resistance acquisition under ARV selective pressure are discussed. Clinical responses to ARV therapy and associated confounding factors are also analyzed in the context of infections by distinct HIV genetic variants.

Genomes of Salmonella with diverse patterns of antibiotic resistance (AR) revealed the dynamics of AR gene organization and detected resistance gene families found in Salmonella

USDA-ARS?s Scientific Manuscript database

We produced and assembled high quality draft genomes (~100X coverage) for 305 Salmonella from a diverse a group of over 100 serovars and diverse sources. Of these isolates, 119 were selected to capture a wide variety of different AR patterns. In our subsequent analyses we included 285 additional pub...

Dynamics of transpiration, sap flow and use of stored water in tropical forest canopy trees.

Treesearch

Frederick C. Meinzer; Shelley A. James; Guillermo Goldstein

2004-01-01

In large trees the daily onset of transpiration causes water to be withdrawn from internal storage compartments resulting in lags between changes in transpiration and sap flow at the base of the tree. We measured time courses of sap flow, hydraulic resistance, plant water potential and stomatal resistance in co-occuring tropical forest canopy trees with trunk diameters...

Solar concentrator materials development

NASA Technical Reports Server (NTRS)

Morel, D. E.; Ayers, S. R.; Gulino, D. A.; Tennyson, R. C.; Egger, R. A.

1986-01-01

Materials with potential applications in reflective and refractive solar dynamic concentrators are tested for resistance to atomic oxygen degradation. It is found that inorganic coatings such as MgF2, SiO(x), and ITO provide excellent protection for reflective surfaces while organic materials are much more susceptible to erosion and mass loss. Of the organic polymers tested, the silicones have the highest intrinsic resistance to atomic oxygen degradation.

Engagement and Resistance at Last Chance High: A Case Study of Twenty-First-Century Literacies and Identities in One English Classroom

ERIC Educational Resources Information Center

Hines, Mary Beth; Kersulov, Michael

2015-01-01

This article investigates the nature of student resistance to and engagement with digital media and twenty-first-century literacies in the English classroom at Last Chance High, an alternative high school. It traces the dynamic interplay of literacy practices and identity performances with and around digital media, exploring one student's…

Carbon nanotube film interlayer for strain and damage sensing in composites during dynamic compressive loading

NASA Astrophysics Data System (ADS)

Wu, A. S.; Na, W.-J.; Yu, W.-R.; Byun, J.-H.; Chou, T.-W.

2012-11-01

A major challenge in the damage assessment of materials under dynamic, high strain rate loading lies in the inability to apply most health monitoring methodologies to the analysis and evaluation of damage incurred on short timescales. Here, we present a resistance-based sensing method utilizing an electrically conductive carbon nanotube film in a fiberglass/vinyl ester composite. This method reveals that applied strain and damage in the form of matrix cracking and delamination give rise to electrical resistance increases across the composite specimen; these can be measured in real-time during high strain rate loading. Damage within the composite specimens is confirmed through pre- and post-mortem x-ray micro computed tomography imaging.

History-dependent dissipative vortex dynamics in superconducting arrays

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

Durkin, Malcolm; Mondragon-Shem, Ian; Eley, Serena Merteen

In this study, we perform current (I)-voltage (V) measurements on low resistance superconductor-normal-superconductor arrays in finite magnetic fields, focusing on the dilute vortex population regime. We observe significant deviations from predicted behavior, notably the absence of a differential resistance peak near the vortex depinning current, and a broad linear I-V region with an extrapolated I intercept equal to the depinning current. Comparing these results to an overdamped molecular vortex model, we find that this behavior can be explained by the presence of a history-dependent dissipative force. Lastly, this approach has not been considered previously, to our knowledge, yet it ismore » crucial for obtaining a correct description of the vortex dynamics in superconducting arrays.« less

History-dependent dissipative vortex dynamics in superconducting arrays

DOE PAGES

Durkin, Malcolm; Mondragon-Shem, Ian; Eley, Serena Merteen; ...

2016-07-14

In this study, we perform current (I)-voltage (V) measurements on low resistance superconductor-normal-superconductor arrays in finite magnetic fields, focusing on the dilute vortex population regime. We observe significant deviations from predicted behavior, notably the absence of a differential resistance peak near the vortex depinning current, and a broad linear I-V region with an extrapolated I intercept equal to the depinning current. Comparing these results to an overdamped molecular vortex model, we find that this behavior can be explained by the presence of a history-dependent dissipative force. Lastly, this approach has not been considered previously, to our knowledge, yet it ismore » crucial for obtaining a correct description of the vortex dynamics in superconducting arrays.« less

Rate & Microstructure Influence on Fracture of WC-Co/Ni Composites

NASA Astrophysics Data System (ADS)

Lamberson, Leslie

2017-06-01

Tungsten carbide metal matrix composites contain ceramic grains of tungsten carbide within a binder of cobalt (Co) or nickel (Ni), allowing the material to have advantageous properties of both metals and ceramics including higher resistance to fracture than most structural ceramics, and higher resistance to permanent deformation than most engineering metals. Due to these performance advantages, WC composites are of interest in drilling, manufacturing tools, and defense penetrator applications, to name a few. Under quasi-static conditions, these hardmetals have been shown to generally exhibit an increase in fracture toughness with an increase in mean free path in the binder phase, and an increase in hardness and wear resistance with a decrease in WC grain size; yet relatively little is known in regards to their dynamic response. Here we present the fracture behavior of WC metal matrix composites under three extreme loading conditions: (1) a single-strike acceleration loading to characterize classical dynamic crack tip energetics via stress intensity factors (SIFs) (2) the impact fatigue, or sub-catastrophic repetitive strikes to failure, and (3) the dynamic crack interactions with normal impact over 1 km/s using an in-house combustionless two-stage light-gas gun. All investigations are conducted using ultra high-speed imaging with full-field measurements from digital image correlation (DIC), and post-mortem scanning electron microscopy. Preliminary results for (1) show that the dynamic fracture toughness increases by a factor of 1.22 to 1.65 over quasi-static, regardless of the binder or grain size investigated. Supported by the American Chemical Society Petroleum Research Fund No. 55860-ND10.

Critical load: a novel approach to determining a sustainable intensity during resistance exercise.

PubMed

Arakelian, Vivian M; Mendes, Renata G; Trimer, Renata; Rossi Caruso, Flavia C; de Sousa, Nuno M; Borges, Vanessa C; do Valle Gomes Gatto, Camila; Baldissera, Vilmar; Arena, Ross; Borghi-Silva, Audrey

2017-05-01

A hyperbolic function as well as a linear relationship between power output and time to exhaustion (Tlim) has been consistently observed during dynamic non-resistive exercises. However, little is known about its concept to resistance exercises (RE), which could be defined as critical load (CL). This study aimed to verify the existence of CL during dynamic RE and to verify the number of workbouts necessary to determine the optimal modeling to achieve it. Fifteen healthy men (23±2.5 yrs) completed 1 repetition maximum test (1RM) on a leg press and 3 (60%, 75% and 90% of 1RM) or 4 (+ 30% of 1RM) workbouts protocols to obtain the CL by hyperbolic and linear regression models between Tlim and load performed. Blood lactate and leg fatigue were also measured. CL was obtained during RE and 3 workbouts protocol estimate it at 53% while 4 tests at 38% of 1 RM. However, based on coefficients of determination, 3 protocols provided a better fit than the 4-parameter model, respectively (R2>0.95 vs. >0.77). Moreover, all intensities increased blood lactate and leg fatigue, however, when corrected by Tlim, were significantly lower at CL. It was possible to determinate CL during dynamic lower limbs RE and that 3 exhaustive workbouts can be used to better estimate the CL, constituting a new concept of determining this threshold during dynamic RE and reducing the physically demanding nature of the protocol. These findings may have important applications for functional performance evaluation and prescription of RE programs.

Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir

PubMed Central

Yu, Yuqi; Wang, Jinan; Shao, Qiang; Shi, Jiye; Zhu, Weiliang

2015-01-01

Molecular dynamics simulations are performed to investigate the dynamic properties of wild-type HIV-1 protease and its two multi-drug-resistant variants (Flap + (L10I/G48V/I54V/V82A) and Act (V82T/I84V)) as well as their binding with APV and DRV inhibitors. The hydrophobic interactions between flap and 80 s (80’s) loop residues (mainly I50-I84’ and I50’-I84) play an important role in maintaining the closed conformation of HIV-1 protease. The double mutation in Act variant weakens the hydrophobic interactions, leading to the transition from closed to semi-open conformation of apo Act. APV or DRV binds with HIV-1 protease via both hydrophobic and hydrogen bonding interactions. The hydrophobic interactions from the inhibitor is aimed to the residues of I50 (I50’), I84 (I84’), and V82 (V82’) which create hydrophobic core clusters to further stabilize the closed conformation of flaps, and the hydrogen bonding interactions are mainly focused with the active site of HIV-1 protease. The combined change in the two kinds of protease-inhibitor interactions is correlated with the observed resistance mutations. The present study sheds light on the microscopic mechanism underlying the mutation effects on the dynamics of HIV-1 protease and the inhibition by APV and DRV, providing useful information to the design of more potent and effective HIV-1 protease inhibitors. PMID:26012849

The role of healthcare strategies in controlling antibiotic resistance.

PubMed

Aziz, Ann-Marie

In an interview in March 2013, the Chief Medical Officer described antibiotic resistance as a 'ticking time bomb' and ranked it along with terrorism on a list of threats to the nation. Her report Infections and the Rise of Antimicrobial Resistance (Department of Health, 2011) highlighted that, while a new infectious disease has been discovered nearly every year over the past three decades, there have been very few new antibiotics developed, leaving our armoury nearly empty. Antibiotic resistance is a universal problem that needs to be tackled by a wide variety of strategies and players. Our approach to tackling resistance to antibiotic agents must therefore also be dynamic. As well as reducing environmental use, we also need to lower antibiotic use in the healthcare setting. Healthcare workers have a huge role to play in combating antibiotic resistance. This article focuses on several issues related to antibiotic resistance, including antibiotic modes of action and the properties that confer resistance on bacteria. It includes information on antibiotic usage and describes current healthcare strategies we can adopt to help reduce the development of resistance.

Deconstructing Temperature Gradients across Fluid Interfaces: The Structural Origin of the Thermal Resistance of Liquid-Vapor Interfaces

NASA Astrophysics Data System (ADS)

Muscatello, Jordan; Chacón, Enrique; Tarazona, Pedro; Bresme, Fernando

2017-07-01

The interfacial thermal resistance determines condensation-evaporation processes and thermal transport across material-fluid interfaces. Despite its importance in transport processes, the interfacial structure responsible for the thermal resistance is still unknown. By combining nonequilibrium molecular dynamics simulations and interfacial analyses that remove the interfacial thermal fluctuations we show that the thermal resistance of liquid-vapor interfaces is connected to a low density fluid layer that is adsorbed at the liquid surface. This thermal resistance layer (TRL) defines the boundary where the thermal transport mechanism changes from that of gases (ballistic) to that characteristic of dense liquids, dominated by frequent particle collisions involving very short mean free paths. We show that the thermal conductance is proportional to the number of atoms adsorbed in the TRL, and hence we explain the structural origin of the thermal resistance in liquid-vapor interfaces.

Insulin Resistance and Mitochondrial Dysfunction.

PubMed

Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

2017-01-01

Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

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

Ke, Ruian; Loverdo, Claude; Qi, Hangfei

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensatemore » when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.« less

The human gut resistome.

PubMed

van Schaik, Willem

2015-06-05

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota ('the gut resistome'). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.

The human gut resistome

PubMed Central

van Schaik, Willem

2015-01-01

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium. PMID:25918444

Experimental evaluation of cyclic fatigue resistance of four different nickel-titanium instruments after immersion in sodium hypochlorite and/or sterilization

PubMed Central

BULEM, Üreyen Kaya; KECECI, Ayse Diljin; GULDAS, Hilmi Egemen

2013-01-01

NiTi instruments have a high risk of separation due to torsional or flexural fatigue (cyclic fatigue). Chemomechanical preparation, cleaning procedures, chemical disinfection and sterilization cause the corrosion of endodontic instruments that may weaken the fracture resistance of the instruments. Objective To assess the effects of NaOCl immersion and autoclave sterilization on the cyclic fatigue resistance of ProFile, FlexMaster, Mtwo and TwistedFiles NiTi instruments (tip size 25, 0.06 taper, n=160). Material and Methods The instruments (n=10 for each subgroup) were dynamically immersed in NaOCl; immersed in NaOCl and sterilized in one autoclave cycle; 5 cycles immersed in NaOCl and sterilized in autoclave and not immersed in NaOCl and not sterilized (control group). Dynamic cyclic fatigue resistance was tested. The number of cycles to failure (NCF) were statistically analyzed (P<0.05). Results Kruskall-Wallis test indicated significant differences among the tested instruments in terms of NCF (P=0.000). The mean NCF of Mtwo (556.75) was higher than that of the Twisted File, Flexmaster and ProFile, 483.1, 376.12, 365.25, respectively. NaOCl immersion and autoclave sterilization have no effect on the NCF values of the tested instruments (P>.05). Conclusions Cyclic fatigue resistance of the tested NiTi instruments cannot be adversely affected by NaOCl immersion and autoclave sterilization. Production process (TwistedFiles) or design (Twisted Files, FlexMaster, Mtwo and ProFile) of the instruments can influence their cyclic fatigue resistance. PMID:24473715

Assessment of Cottle's areas through the application of a mathematical model deriving from acoustic rhinometry and rhinomanometric data.

PubMed

Zambetti, G; Filiaci, F; Romeo, R; Soldo, P; Filiaci, F

2005-04-01

Each nasal area, as defined by Cottle, has a different influence on the nasal airflow. The longitudinal distribution of resistances in nasal cavities was calculated by the anterior rhinomanometry and acoustic rhinometry data. Dynamic study of Cottle's areas in normal subjects was carried out by rhinomanometry and acoustic rhinometry. Study by the Department of Otolaryngology of the University of Rome-La Sapienza. Twenty-seven Caucasian adults in local and general healthy conditions took part and completed this study, with a total of 54 nasal cavities included because of negativity at ENT-examination and clinical history, with normal respiratory parameters at the rhinomanometry and acoustic rhinometry. We determined nasal and acoustic resistances, nasal volumes and cross-sectional surface areas, as defined by Cottle, using nasal endoscopy. The longitudinal distribution of nasal resistances was obtained by integrating experimental surface areas using a novel mathematical model. The estimation of the longitudinal nasal resistance variations as a result of a theoretical reduction of the surface areas. The reduction of the 2-3-1 areas (in this order of importance) showed the greatest influence on the nasal resistances with coefficients of determinations greater than 0.98, this being quite different from that of the areas 4 and 5 for quite smaller area reduction percentages. The areas 2-3-1 control the overall nasal resistance so the surgical procedures on these areas greatly influence the dynamics of nasal airflow. The mathematical model developed here gives useful information to nasal functional surgery and may be applied to other schemes of nasal cavity.

Estimating HIV-1 Fitness Characteristics from Cross-Sectional Genotype Data

PubMed Central

Gopalakrishnan, Sathej; Montazeri, Hesam; Menz, Stephan; Beerenwinkel, Niko; Huisinga, Wilhelm

2014-01-01

Despite the success of highly active antiretroviral therapy (HAART) in the management of human immunodeficiency virus (HIV)-1 infection, virological failure due to drug resistance development remains a major challenge. Resistant mutants display reduced drug susceptibilities, but in the absence of drug, they generally have a lower fitness than the wild type, owing to a mutation-incurred cost. The interaction between these fitness costs and drug resistance dictates the appearance of mutants and influences viral suppression and therapeutic success. Assessing in vivo viral fitness is a challenging task and yet one that has significant clinical relevance. Here, we present a new computational modelling approach for estimating viral fitness that relies on common sparse cross-sectional clinical data by combining statistical approaches to learn drug-specific mutational pathways and resistance factors with viral dynamics models to represent the host-virus interaction and actions of drug mechanistically. We estimate in vivo fitness characteristics of mutant genotypes for two antiretroviral drugs, the reverse transcriptase inhibitor zidovudine (ZDV) and the protease inhibitor indinavir (IDV). Well-known features of HIV-1 fitness landscapes are recovered, both in the absence and presence of drugs. We quantify the complex interplay between fitness costs and resistance by computing selective advantages for different mutants. Our approach extends naturally to multiple drugs and we illustrate this by simulating a dual therapy with ZDV and IDV to assess therapy failure. The combined statistical and dynamical modelling approach may help in dissecting the effects of fitness costs and resistance with the ultimate aim of assisting the choice of salvage therapies after treatment failure. PMID:25375675

Exploring resistance mechanisms of HCV NS3/4A protease mutations to MK5172: insight from molecular dynamics simulations and free energy calculations.

PubMed

Guan, Yan; Sun, Huiyong; Pan, Peichen; Li, Youyong; Li, Dan; Hou, Tingjun

2015-09-01

Mutations at a number of key positions (Ala156, Asp168 and Arg155) of the HCV NS3/4A protease can induce medium to high resistance to MK5172. The emergence of the resistant mutations seriously compromises the antiviral therapy efficacy to hepatitis C. In this study, molecular dynamics (MD) simulations, free energy calculations and free energy decomposition were used to explore the interaction profiles of MK5172 with the wild-type (WT) and four mutated (R155K, D168A, D168V and A156T) HCV NS3/4A proteases. The binding free energies predicted by Molecular Mechanics/Generalized Born Solvent Area (MM/GBSA) are consistent with the trend of the experimental drug resistance data. The free energy decomposition analysis shows that the resistant mutants may change the protein-MK5172 interaction profiles, resulting in the unbalanced energetic distribution amongst the catalytic triad, the strand 135-139 and the strand 154-160. Moreover, umbrella sampling (US) simulations were employed to elucidate the unbinding processes of MK5172 from the active pockets of the WT HCV NS3/4A protease and the four mutants. The US simulations demonstrate that the dissociation pathways of MK5172 escaping from the binding pockets of the WT and mutants are quite different, and it is quite possible that MK5172 will be harder to get access to the correct binding sites of the mutated proteases, thereafter leading to drug resistance.

On cell resistance and immune response time lag in a model for the HIV infection

NASA Astrophysics Data System (ADS)

Solovey, Guillermo; Peruani, Fernando; Ponce Dawson, Silvina; Maria Zorzenon dos Santos, Rita

2004-11-01

Recently, a cellular automata model has been introduced (Phys. Rev. Lett. 87 (2001) 168102) to describe the spread of the HIV infection among target cells in lymphoid tissues. The model reproduces qualitatively the entire course of the infection displaying, in particular, the two time scales that characterize its dynamics. In this work, we investigate the robustness of the model against changes in three of its parameters. Two of them are related to the resistance of the cells to get infected. The other one describes the time interval necessary to mount specific immune responses. We have observed that an increase of the cell resistance, at any stage of the infection, leads to a reduction of the latency period, i.e., of the time interval between the primary infection and the onset of AIDS. However, during the early stages of the infection, when the cell resistance increase is combined with an increase in the initial concentration of infected cells, the original behavior is recovered. Therefore we find a long and a short latency regime (eight and one year long, respectively) depending on the value of the cell resistance. We have obtained, on the other hand, that changes on the parameter that describes the immune system time lag affects the time interval during which the primary infection occurs. Using different extended versions of the model, we also discuss how the two-time scale dynamics is affected when we include inhomogeneities on the cells properties, as for instance, on the cell resistance or on the time interval to mount specific immune responses.

The dynamics of cereal cyst nematode infection differ between susceptible and resistant barley cultivars and lead to changes in (1,3;1,4)-β-glucan levels and HvCslF gene transcript abundance.

PubMed

Aditya, Jessika; Lewis, John; Shirley, Neil J; Tan, Hwei-Ting; Henderson, Marilyn; Fincher, Geoffrey B; Burton, Rachel A; Mather, Diane E; Tucker, Matthew R

2015-07-01

Heterodera avenae (cereal cyst nematode, CCN) infects the roots of barley (Hordeum vulgare) forming syncytial feeding sites. In resistant host plants, relatively few females develop to maturity. Little is known about the physiological and biochemical changes induced during CCN infection. Responses to CCN infection were investigated in resistant (Rha2) and susceptible barley cultivars through histological, compositional and transcriptional analysis. Two phases were identified that influence CCN viability, including feeding site establishment and subsequent cyst maturation. Syncytial development progressed faster in the resistant cultivar Chebec than in the susceptible cultivar Skiff, and was accompanied by changes in cell wall polysaccharide abundance, particularly (1,3;1,4)-β-glucan. Transcriptional profiling identified several glycosyl transferase genes, including CELLULOSE SYNTHASE-LIKE F10 (HvCslF10), which may contribute to differences in polysaccharide abundance between resistant and susceptible cultivars. In barley, Rha2-mediated CCN resistance drives rapid deterioration of CCN feeding sites, specific changes in cell wall-related transcript abundance and changes in cell wall composition. During H. avenae infection, (1,3;1,4)-β-glucan may influence CCN feeding site development by limiting solute flow, similar to (1,3)-β-glucan during dicot cyst nematode infections. Dynamic transcriptional changes in uncharacterized HvCslF genes, possibly involved in (1,3;1,4)-β-glucan synthesis, suggest a role for these genes in the CCN infection process. © 2015 The University of Adelaide. New Phytologist © 2015 New Phytologist Trust.

Imaging groundwater infiltration dynamics in the karst vadose zone with long-term ERT monitoring

NASA Astrophysics Data System (ADS)

Watlet, Arnaud; Kaufmann, Olivier; Triantafyllou, Antoine; Poulain, Amaël; Chambers, Jonathan E.; Meldrum, Philip I.; Wilkinson, Paul B.; Hallet, Vincent; Quinif, Yves; Van Ruymbeke, Michel; Van Camp, Michel

2018-03-01

Water infiltration and recharge processes in karst systems are complex and difficult to measure with conventional hydrological methods. In particular, temporarily saturated groundwater reservoirs hosted in the vadose zone can play a buffering role in water infiltration. This results from the pronounced porosity and permeability contrasts created by local karstification processes of carbonate rocks. Analyses of time-lapse 2-D geoelectrical imaging over a period of 3 years at the Rochefort Cave Laboratory (RCL) site in south Belgium highlight variable hydrodynamics in a karst vadose zone. This represents the first long-term and permanently installed electrical resistivity tomography (ERT) monitoring in a karst landscape. The collected data were compared to conventional hydrological measurements (drip discharge monitoring, soil moisture and water conductivity data sets) and a detailed structural analysis of the local geological structures providing a thorough understanding of the groundwater infiltration. Seasonal changes affect all the imaged areas leading to increases in resistivity in spring and summer attributed to enhanced evapotranspiration, whereas winter is characterised by a general decrease in resistivity associated with a groundwater recharge of the vadose zone. Three types of hydrological dynamics, corresponding to areas with distinct lithological and structural features, could be identified via changes in resistivity: (D1) upper conductive layers, associated with clay-rich soil and epikarst, showing the highest variability related to weather conditions; (D2) deeper and more resistive limestone areas, characterised by variable degrees of porosity and clay contents, hence showing more diffuse seasonal variations; and (D3) a conductive fractured zone associated with damped seasonal dynamics, while showing a great variability similar to that of the upper layers in response to rainfall events. This study provides detailed images of the sources of drip discharge spots traditionally monitored in caves and aims to support modelling approaches of karst hydrological processes.

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

PubMed

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

Effect of a 4-week elastic resistance band training regimen on back kinematics in horses trotting in-hand and on the lunge.

PubMed

Pfau, T; Simons, V; Rombach, N; Stubbs, N; Weller, R

2017-11-01

Training and rehabilitation techniques aiming at improving core muscle strength may result in increased dynamic stability of the equine vertebral column. A system of elastic resistance bands is suggested to provide proprioceptive feedback during motion to encourage recruitment of core abdominal and hindquarter musculature for improved dynamic stability. To quantify the effects of a specific resistance band system on back kinematics during trot in-hand and lungeing at beginning and end of a 4-week exercise programme. Quantitative analysis of back movement before/after a 4-week exercise programme. Inertial sensor data were collected from seven horses at weeks 1 and 4 of an exercise protocol with elastic resistance bands. Translational (dorsoventral, mediolateral) and rotational (roll, pitch) range of motion of six landmarks from poll to coccygeal region were quantified during trot in-hand (hard surface) and during lungeing (soft surface, both reins) with/without elastic exercise bands. A mixed model (P<0.05) evaluated the effects of exercise bands, time (week) and movement direction (straight, left, right). The bands reduced roll, pitch and mediolateral displacement in the thoracolumbar region (all P≤0.04). At week 4, independent of band usage, rotational movement (withers, thoracic) was reduced while dorsoventral movement (thoracic, coccygeal) increased. Increased back movement was measured in 80% of back movement parameters during lungeing. Comparing each horse without and with bands without a control group does not distinguish whether the differences measured between weeks 1 and 4 are related to use of the bands, or only to the exercise regimen. Results suggest that the elastic resistance bands reduce mediolateral and rotational movement of the thoracolumbar region (increase dynamic stability) in trot. Further studies should investigate the underlying mechanism with reference to core abdominal and hindquarter muscle recruitment and study the long-term effects. The Summary is available in Chinese - see Supporting Information. © 2017 EVJ Ltd.

Modelling the transmission of healthcare associated infections: a systematic review

PubMed Central

2013-01-01

Background Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. Methods MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. Results In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries. The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. Conclusions Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models. PMID:23809195

Effect of the Rate of Hot Compressive Deformation on the Kinetics of Dynamic and Static Recrystallization of Novel Medium-Carbon Medium-Alloy Steel

NASA Astrophysics Data System (ADS)

Khlusova, E. I.; Zisman, A. A.; Knyazyuk, T. V.; Novoskol'tsev, N. N.

2018-03-01

Dynamic and static recrystallization occurring under hot deformation at a rate of 1 and 100 sec - 1 in high-strength medium-carbon wear-resistant steels developed at CRISM "Prometey" for die forming of parts of driven elements of tillage machines is studied. The critical strain of dynamic recrystallization and the threshold temperatures and times of finish of static recrystallization are determined for the studied deformation rates at various temperatures.

Analysis encapsulation of fiber Bragg gratings into polydimethylsiloxane for the needs of dynamic weighing

NASA Astrophysics Data System (ADS)

Fajkus, M.; Nedoma, J.; Martinek, R.; Novak, M.; Jargus, J.; Vasinek, V.

2017-05-01

Authors of the article focused on the possible encapsulation method of fiber Bragg gratings (FBGs) for the needs of dynamic weighing. For monitoring the parameters, we used broad-spectrum light source LED (Light-Emitting Diode) with a central wavelength of 1550 nm and optical spectrum analyzer with sampling rate 300 Hz. For encapsulation of used FBGs was chosen a specific material polymer polydimethylsiloxane (PDMS). A characteristic feature of this material is very high mechanical resistance, chemical resistance and temperature stability in the range of values -60 °C to + 200 °C. The combination of characteristic advantages of optical fibers (electromagnetic immunity) with stated properties of PDMS gives us the innovative type of encapsulated sensor which could be used for example for the needs of dynamic weighing in worsened or potentially hazardous conditions. This type of monitoring weighing is fully dielectric. Experimental measurements were carried out in laboratory conditions in the weight range of 35 up to 180 kg.

Understanding the Basis of Drug Resistance of the Mutants of αβ-Tubulin Dimer via Molecular Dynamics Simulations

PubMed Central

Natarajan, Kathiresan; Senapati, Sanjib

2012-01-01

The vital role of tubulin dimer in cell division makes it an attractive drug target. Drugs that target tubulin showed significant clinical success in treating various cancers. However, the efficacy of these drugs is attenuated by the emergence of tubulin mutants that are unsusceptible to several classes of tubulin binding drugs. The molecular basis of drug resistance of the tubulin mutants is yet to be unraveled. Here, we employ molecular dynamics simulations, protein-ligand docking, and MMPB(GB)SA analyses to examine the binding of anticancer drugs, taxol and epothilone to the reported point mutants of tubulin - T274I, R282Q, and Q292E. Results suggest that the mutations significantly alter the tubulin structure and dynamics, thereby weaken the interactions and binding of the drugs, primarily by modifying the M loop conformation and enlarging the pocket volume. Interestingly, these mutations also affect the tubulin distal sites that are associated with microtubule building processes. PMID:22879949

Memory effects in stock price dynamics: evidences of technical trading

PubMed Central

Garzarelli, Federico; Cristelli, Matthieu; Pompa, Gabriele; Zaccaria, Andrea; Pietronero, Luciano

2014-01-01

Technical trading represents a class of investment strategies for Financial Markets based on the analysis of trends and recurrent patterns in price time series. According standard economical theories these strategies should not be used because they cannot be profitable. On the contrary, it is well-known that technical traders exist and operate on different time scales. In this paper we investigate if technical trading produces detectable signals in price time series and if some kind of memory effects are introduced in the price dynamics. In particular, we focus on a specific figure called supports and resistances. We first develop a criterion to detect the potential values of supports and resistances. Then we show that memory effects in the price dynamics are associated to these selected values. In fact we show that prices more likely re-bounce than cross these values. Such an effect is a quantitative evidence of the so-called self-fulfilling prophecy, that is the self-reinforcement of agents' belief and sentiment about future stock prices' behavior. PMID:24671011

Integrated Joule switches for the control of current dynamics in parallel superconducting strips

NASA Astrophysics Data System (ADS)

Casaburi, A.; Heath, R. M.; Cristiano, R.; Ejrnaes, M.; Zen, N.; Ohkubo, M.; Hadfield, R. H.

2018-06-01

Understanding and harnessing the physics of the dynamic current distribution in parallel superconducting strips holds the key to creating next generation sensors for single molecule and single photon detection. Non-uniformity in the current distribution in parallel superconducting strips leads to low detection efficiency and unstable operation, preventing the scale up to large area sensors. Recent studies indicate that non-uniform current distributions occurring in parallel strips can be understood and modeled in the framework of the generalized London model. Here we build on this important physical insight, investigating an innovative design with integrated superconducting-to-resistive Joule switches to break the superconducting loops between the strips and thus control the current dynamics. Employing precision low temperature nano-optical techniques, we map the uniformity of the current distribution before- and after the resistive strip switching event, confirming the effectiveness of our design. These results provide important insights for the development of next generation large area superconducting strip-based sensors.

System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors

NASA Technical Reports Server (NTRS)

Aljuri, A. N.; Bursac, N.; Marini, R.; Cohen, R. J.

2001-01-01

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals. Grant numbers: NAG5-4989. c 2001. Elsevier Science Ltd. All rights reserved.

Memory effects in stock price dynamics: evidences of technical trading

NASA Astrophysics Data System (ADS)

Garzarelli, Federico; Cristelli, Matthieu; Pompa, Gabriele; Zaccaria, Andrea; Pietronero, Luciano

2014-03-01

Technical trading represents a class of investment strategies for Financial Markets based on the analysis of trends and recurrent patterns in price time series. According standard economical theories these strategies should not be used because they cannot be profitable. On the contrary, it is well-known that technical traders exist and operate on different time scales. In this paper we investigate if technical trading produces detectable signals in price time series and if some kind of memory effects are introduced in the price dynamics. In particular, we focus on a specific figure called supports and resistances. We first develop a criterion to detect the potential values of supports and resistances. Then we show that memory effects in the price dynamics are associated to these selected values. In fact we show that prices more likely re-bounce than cross these values. Such an effect is a quantitative evidence of the so-called self-fulfilling prophecy, that is the self-reinforcement of agents' belief and sentiment about future stock prices' behavior.

Structures and transport dynamics of a Campylobacter jejuni multidrug efflux pump

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

Su, Chih-Chia; Yin, Linxiang; Kumar, Nitin

2017-08-01

Resistance-nodulation-cell division efflux pumps are integral membrane proteins that catalyze the export of substrates across cell membranes. Within the hydrophobe-amphiphile efflux subfamily, these resistance-nodulation-cell division proteins largely form trimeric efflux pumps. The drug efflux process has been proposed to entail a synchronized motion between subunits of the trimer to advance the transport cycle, leading to the extrusion of drug molecules. Here we use X-ray crystallography and single-molecule fluorescence resonance energy transfer imaging to elucidate the structures and functional dynamics of the Campylobacter jejuni CmeB multidrug efflux pump. We find that the CmeB trimer displays a very unique conformation. A directmore » observation of transport dynamics in individual CmeB trimers embedded in membrane vesicles indicates that each CmeB subunit undergoes conformational transitions uncoordinated and independent of each other. On the basis of our findings and analyses, we propose a model for transport mechanism where CmeB protomers function independently within the trimer.« less

Acquired EGFR L718V mutation mediates resistance to osimertinib in non-small cell lung cancer but retains sensitivity to afatinib.

PubMed

Liu, Yutao; Li, Yan; Ou, Qiuxiang; Wu, Xue; Wang, Xiaonan; Shao, Yang W; Ying, Jianming

2018-04-01

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are promising targeted therapies for EGFR-mutated non-small-cell lung cancer (NSCLC) patients. However, acquired resistance inevitably develops. Comprehensive and dynamic companion genomic diagnosis can gain insights into underlying resistance mechanisms, thereby help oncologists and patients to make informed decision on the potential benefit of the treatment. A 67-year-old male who was initially diagnosed of EGFR L858R-mediated NSCLC received multiple lines of chemotherapy and EGFR TKI therapies after surgery. The EGFR mutational status of individual metastatic lesion was determined by genetic testing of the tumor tissue biopsies using next generation sequencing (NGS) throughout the patient's clinical course. An acquired potentially drug-resistant EGFR mutation was functionally validated in vitro and its sensitivity to different EGFR TKIs was assessed simultaneously. We have identified distinct resistance mechanisms to EGFR blockade in different metastatic lung lesions. Acquired EGFR T790M was first detected that leads to the resistance to the gefitinib treatment. Consequently, osimertinib was administrated and the response lasted until disease progressed. We identified a newly acquired EGFR L718V mutation in one lesion in conjunction with L858R, but not T790M, which showed stable disease on the following erlotinib treatment, while EGFR C797S together with L858R/T790M was detected in the other lesion that continuously progressed. In vitro functional studies demonstrated that EGFR-L858R/L718V confers resistance to osimertinib, but retains sensitivity to the second generation TKI afatinib. We reported that distinct resistance mechanisms could arise in different metastases within the same patient in response to EGFR blockade. We also demonstrated in vitro that EGFR L718V mutation mediates resistance to osimertinib, but retains sensitivity to afatinib. We evidenced that dynamic companion genomic diagnosis offers valuable information to help define the mechanisms of drug resistance and to guide the selection of subsequent treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Exercise is good for your blood pressure: effects of endurance training and resistance training.

PubMed

Fagard, R H

2006-09-01

1. Although several epidemiological studies have not observed significant independent relationships between physical activity or fitness and blood pressure, others have concluded that blood pressure is lower in individuals who are more fit or active. However, longitudinal intervention studies are more appropriate for assessing the effects of physical activity on blood pressure. 2. Previously, we have performed meta-analyses of randomized controlled trials involving dynamic aerobic endurance training or resistance training. Inclusion criteria were: random allocation to intervention and control; physical training as the sole intervention; inclusion of healthy sedentary normotensive and/or hypertensive adults; intervention duration of at least 4 weeks; availability of systolic and/or diastolic blood pressure; and publication in a peer-reviewed journal up to December 2003. 3. The meta-analysis on endurance training involved 72 trials and 105 study groups. After weighting for the number of trained participants, training induced significant net reductions of resting and day time ambulatory blood pressure of 3.0/2.4 mmHg (P < 0.001) and 3.3/3.5 mmHg (P < 0.01), respectively. The reduction of resting blood pressure was more pronounced in the 30 hypertensive study groups (-6.9/-4.9) than in the others (-1.9/-1.6; P < 0.001 for all). Systemic vascular resistance decreased by 7.1% (P < 0.05), plasma noradrenaline by 29% (P < 0.001) and plasma renin activity by 20% (P < 0.05). Bodyweight decreased by 1.2 kg (P < 0.001), waist circumference by 2.8 cm (P < 0.001), percentage body fat by 1.4% (P < 0.001) and the Homeostatic Model Assessment (HOMA) index of insulin resistance by 0.31 units (P < 0.01). High-density lipoprotein-cholesterol increased by 0.032 mmol/L (P < 0.05). 4. Resistance training has been less well studied. A meta-analysis of nine randomized controlled trials (12 study groups) on mostly dynamic resistance training revealed a weighted net reduction of diastolic blood pressure of 3.5 mmHg (P < 0.01) associated with exercise and a non-significant reduction of systolic blood pressure of 3.2 mmHg (P = 0.10). 5. In conclusion, dynamic aerobic endurance training decreases blood pressure through a reduction of systemic vascular resistance, in which the sympathetic nervous system and the renin-angiotensin system appear to be involved, and favourably affects concomitant cardiovascular risk factors. In addition, the few available data suggest that resistance training is able to reduce blood pressure.

BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia.

PubMed

Zabriskie, Matthew S; Eide, Christopher A; Tantravahi, Srinivas K; Vellore, Nadeem A; Estrada, Johanna; Nicolini, Franck E; Khoury, Hanna J; Larson, Richard A; Konopleva, Marina; Cortes, Jorge E; Kantarjian, Hagop; Jabbour, Elias J; Kornblau, Steven M; Lipton, Jeffrey H; Rea, Delphine; Stenke, Leif; Barbany, Gisela; Lange, Thoralf; Hernández-Boluda, Juan-Carlos; Ossenkoppele, Gert J; Press, Richard D; Chuah, Charles; Goldberg, Stuart L; Wetzler, Meir; Mahon, Francois-Xavier; Etienne, Gabriel; Baccarani, Michele; Soverini, Simona; Rosti, Gianantonio; Rousselot, Philippe; Friedman, Ran; Deininger, Marie; Reynolds, Kimberly R; Heaton, William L; Eiring, Anna M; Pomicter, Anthony D; Khorashad, Jamshid S; Kelley, Todd W; Baron, Riccardo; Druker, Brian J; Deininger, Michael W; O'Hare, Thomas

2014-09-08

Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph(+)) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph(+) leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of pyrethroid resistance on the efficacy and effectiveness of bednets for malaria control in Africa

PubMed Central

Churcher, Thomas S; Lissenden, Natalie; Griffin, Jamie T; Worrall, Eve; Ranson, Hilary

2016-01-01

Long lasting pyrethroid treated bednets are the most important tool for preventing malaria. Pyrethroid resistant Anopheline mosquitoes are now ubiquitous in Africa, though the public health impact remains unclear, impeding the deployment of more expensive nets. Meta-analyses of bioassay studies and experimental hut trials are used to characterise how pyrethroid resistance changes the efficacy of standard bednets, and those containing the synergist piperonyl butoxide (PBO), and assess its impact on malaria control. New bednets provide substantial personal protection until high levels of resistance, though protection may wane faster against more resistant mosquito populations as nets age. Transmission dynamics models indicate that even low levels of resistance would increase the incidence of malaria due to reduced mosquito mortality and lower overall community protection over the life-time of the net. Switching to PBO bednets could avert up to 0.5 clinical cases per person per year in some resistance scenarios. DOI: http://dx.doi.org/10.7554/eLife.16090.001 PMID:27547988

System Dynamics Modeling for Public Health: Background and Opportunities

PubMed Central

Homer, Jack B.; Hirsch, Gary B.

2006-01-01

The systems modeling methodology of system dynamics is well suited to address the dynamic complexity that characterizes many public health issues. The system dynamics approach involves the development of computer simulation models that portray processes of accumulation and feedback and that may be tested systematically to find effective policies for overcoming policy resistance. System dynamics modeling of chronic disease prevention should seek to incorporate all the basic elements of a modern ecological approach, including disease outcomes, health and risk behaviors, environmental factors, and health-related resources and delivery systems. System dynamics shows promise as a means of modeling multiple interacting diseases and risks, the interaction of delivery systems and diseased populations, and matters of national and state policy. PMID:16449591

Impact of pre-application treatment on municipal sludge composition, soil dynamics of antibiotic resistance genes, and abundance of antibiotic-resistance genes on vegetables at harvest.

PubMed

Lau, Calvin Ho-Fung; Li, Bing; Zhang, Tong; Tien, Yuan-Ching; Scott, Andrew; Murray, Roger; Sabourin, Lyne; Lapen, David R; Duenk, Peter; Topp, Edward

2017-06-01

In many jurisdictions sludge recovered from the sewage treatment process is a valued fertilizer for crop production. Pre-treatment of sewage sludge prior to land application offers the potential to abate enteric microorganisms that carry genes conferring resistance to antibiotics. Pre-treatment practices that accomplish this should have the desirable effect of reducing the risk of contamination of crops or adjacent water with antibiotic resistance genes carried in these materials. In the present study, we obtained municipal sludge that had been subjected to one of five treatments. There were, anaerobic-digestion or aerobic-digestion, in both instances with and without dewatering; and heat-treatment and pelletization. Each of the five types of biosolids was applied to an agricultural field at commercial rates, following which lettuce, carrots and radishes were planted. Based on qPCR, the estimated antibiotic gene loading rates were comparable with each of the five biosolids. However, the gene abundance in soil following application of the pelletized biosolids was anomalously lower than expected. Following application, the abundance of antibiotic resistance genes decreased in a generally coherent fashion, except sul1 which increased in abundance during the growing season in the soil fertilized with pelletized biosolids. Based on qPCR and high throughput sequencing evidence for transfer of antibiotic resistance genes from the biosolids to the vegetables at harvest was weak. Clostridia were more abundant in soils receiving any of the biosolids except the pelletized. Overall, the behavior of antibiotic resistance genes in soils receiving aerobically or anaerobically-digested biosolids was consistent and coherent with previous studies. However, dynamics of antibiotic resistance genes in soils receiving the heat treated pelletized biosolids were very different, and the underlying mechanisms merit investigation. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Molecular Preadaptation to Antimony Resistance in Leishmania donovani on the Indian Subcontinent

PubMed Central

Imamura, H.; Zander, D.; D’Haenens, E.; Maes, I.; Domagalska, M. A.; Clos, J.

2018-01-01

ABSTRACT Antimonials (Sb) were used for decades for chemotherapy of visceral leishmaniasis (VL). Now abandoned in the Indian subcontinent (ISC) because of Leishmania donovani resistance, this drug offers a unique model for understanding drug resistance dynamics. In a previous phylogenomic study, we found two distinct populations of L. donovani: the core group (CG) in the Gangetic plains and ISC1 in the Nepalese highlands. Sb resistance was only encountered within the CG, and a series of potential markers were identified. Here, we analyzed the development of resistance to trivalent antimonials (SbIII) upon experimental selection in ISC1 and CG strains. We observed that (i) baseline SbIII susceptibility of parasites was higher in ISC1 than in the CG, (ii) time to SbIII resistance was higher for ISC1 parasites than for CG strains, and (iii) untargeted genomic and metabolomic analyses revealed molecular changes along the selection process: these were more numerous in ISC1 than in the CG. Altogether these observations led to the hypothesis that CG parasites are preadapted to SbIII resistance. This hypothesis was experimentally confirmed by showing that only wild-type CG strains could survive a direct exposure to the maximal concentration of SbIII. The main driver of this preadaptation was shown to be MRPA, a gene involved in SbIII sequestration and amplified in an intrachromosomal amplicon in all CG strains characterized so far. This amplicon emerged around 1850 in the CG, well before the implementation of antimonials for VL chemotherapy, and we discuss here several hypotheses of selective pressure that could have accompanied its emergence. IMPORTANCE The “antibiotic resistance crisis” is a major challenge for scientists and medical professionals. This steady rise in drug-resistant pathogens also extends to parasitic diseases, with antimony being the first anti-Leishmania drug that fell in the Indian subcontinent (ISC). Leishmaniasis is a major but neglected infectious disease with limited therapeutic options. Therefore, understanding how parasites became resistant to antimonials is of commanding importance. In this study, we experimentally characterized the dynamics of this resistance acquisition and show for the first time that some Leishmania populations of the ISC were preadapted to antimony resistance, likely driven by environmental factors or by drugs used in the 19th century. PMID:29669889

Modelling the evolution of drug resistance in the presence of antiviral drugs

PubMed Central

Wu, Jianhong; Yan, Ping; Archibald, Chris

2007-01-01

Background The emergence of drug resistance in treated populations and the transmission of drug resistant strains to newly infected individuals are important public health concerns in the prevention and control of infectious diseases such as HIV and influenza. Mathematical modelling may help guide the design of treatment programs and also may help us better understand the potential benefits and limitations of prevention strategies. Methods To explore further the potential synergies between modelling of drug resistance in HIV and in pandemic influenza, the Public Health Agency of Canada and the Mathematics for Information Technology and Complex Systems brought together selected scientists and public health experts for a workshop in Ottawa in January 2007, to discuss the emergence and transmission of HIV antiviral drug resistance, to report on progress in the use of mathematical models to study the emergence and spread of drug resistant influenza viral strains, and to recommend future research priorities. Results General lectures and round-table discussions were organized around the issues on HIV drug resistance at the population level, HIV drug resistance in Western Canada, HIV drug resistance at the host level (with focus on optimal treatment strategies), and drug resistance for pandemic influenza planning. Conclusion Some of the issues related to drug resistance in HIV and pandemic influenza can possibly be addressed using existing mathematical models, with a special focus on linking the existing models to the data obtained through the Canadian HIV Strain and DR Surveillance Program. Preliminary statistical analysis of these data carried out at PHAC, together with the general model framework developed by Dr. Blower and her collaborators, should provide further insights into the mechanisms behind the observed trends and thus could help with the prediction and analysis of future trends in the aforementioned items. Remarkable similarity between dynamic, compartmental models for the evolution of wild and drug resistance strains of both HIV and pandemic influenza may provide sufficient common ground to create synergies between modellers working in these two areas. One of the key contributions of mathematical modeling to the control of infectious diseases is the quantification and design of optimal strategies, combining techniques of operations research with dynamic modeling would enhance the contribution of mathematical modeling to the prevention and control of infectious diseases. PMID:17953775

Modelling the evolution of drug resistance in the presence of antiviral drugs.

PubMed

Wu, Jianhong; Yan, Ping; Archibald, Chris

2007-10-23

The emergence of drug resistance in treated populations and the transmission of drug resistant strains to newly infected individuals are important public health concerns in the prevention and control of infectious diseases such as HIV and influenza. Mathematical modelling may help guide the design of treatment programs and also may help us better understand the potential benefits and limitations of prevention strategies. To explore further the potential synergies between modelling of drug resistance in HIV and in pandemic influenza, the Public Health Agency of Canada and the Mathematics for Information Technology and Complex Systems brought together selected scientists and public health experts for a workshop in Ottawa in January 2007, to discuss the emergence and transmission of HIV antiviral drug resistance, to report on progress in the use of mathematical models to study the emergence and spread of drug resistant influenza viral strains, and to recommend future research priorities. General lectures and round-table discussions were organized around the issues on HIV drug resistance at the population level, HIV drug resistance in Western Canada, HIV drug resistance at the host level (with focus on optimal treatment strategies), and drug resistance for pandemic influenza planning. Some of the issues related to drug resistance in HIV and pandemic influenza can possibly be addressed using existing mathematical models, with a special focus on linking the existing models to the data obtained through the Canadian HIV Strain and DR Surveillance Program. Preliminary statistical analysis of these data carried out at PHAC, together with the general model framework developed by Dr. Blower and her collaborators, should provide further insights into the mechanisms behind the observed trends and thus could help with the prediction and analysis of future trends in the aforementioned items. Remarkable similarity between dynamic, compartmental models for the evolution of wild and drug resistance strains of both HIV and pandemic influenza may provide sufficient common ground to create synergies between modellers working in these two areas. One of the key contributions of mathematical modeling to the control of infectious diseases is the quantification and design of optimal strategies, combining techniques of operations research with dynamic modeling would enhance the contribution of mathematical modeling to the prevention and control of infectious diseases.

Type of fitness cost influences the rate of evolution of resistance to transgenic Bt crops.

PubMed

Hackett, Sean C; Bonsall, Michael B

2016-10-01

The evolution of resistance to pesticides by insect pests is a significant challenge for sustainable agriculture. For transgenic crops expressing Bacillus thuringiensis (Bt), crystalline (Cry) toxins resistance evolution may be delayed by the high-dose/refuge strategy in which a non-toxic refuge is planted to promote the survival of susceptible insects. The high-dose/refuge strategy may interact with fitness costs associated with resistance alleles to further delay resistance. However, while a diverse range of fitness costs are reported in the field, they are typically represented as a fixed reduction in survival or viability which is insensitive to ecological conditions such as competition. Furthermore, the potential dynamic consequences of restricting susceptible insects to a refuge which represents only a fraction of the available space have rarely been considered.We present a generalized discrete time model which utilizes dynamic programming methods to derive the optimal management decisions for the control of a theoretical insect pest population exposed to Bt crops. We consider three genotypes (susceptible homozygotes, resistant homozygotes and heterozygotes) and implement fitness costs of resistance to Bt toxins as either a decrease in the relative competitive ability of resistant insects or as a penalty on fecundity. Model analysis is repeated and contrasted for two types of density dependence: uniform density dependence which operates equally across the landscape and heterogeneous density dependence where the intensity of competition scales inversely with patch size and is determined separately for the refuge and Bt crop.When the planting of Bt is decided optimally, fitness costs to fecundity allow for the planting of larger areas of Bt crops than equivalent fitness costs that reduce the competitive ability of resistant insects.Heterogeneous competition only influenced model predictions when the proportional area of Bt planted in each season was decided optimally and resistance was not recessive. Synthesis and applications . The high-dose/refuge strategy alone is insufficient to preserve susceptibility to transgenic Bacillus thuringiensis (Bt) crops in the long term when constraints upon the evolution of resistance are not insurmountable. Fitness costs may enhance the delaying effect of the refuge, but the extent to which they do so depends upon how the cost is realized biologically. Fitness costs which apply independently of other variables may be more beneficial to resistance management than costs which are only visible to selection under a limited range of ecological conditions.

Alternate attractors in the population dynamics of a tree-killing bark beetle

Treesearch

Sharon J. Martinson; Tiina Ylioja; Brian T. Sullivan; Ronald F. Billings; Matthew P. Ayres

2013-01-01

Among the most striking changes in ecosystems are those that happen abruptly and resist return to the original condition (i.e., regime shifts). This frequently involves conspicuous changes in the abundance of one species (e.g., an outbreaking pest or keystone species). Alternate attractors in population dynamics could explain switches between low and high levels of...

Invariants of the Axisymmetric Plasma Flows

NASA Astrophysics Data System (ADS)

Bogoyavlenskij, Oleg

2018-06-01

Infinite families of new functionally independent invariants are derived for the axisymmetric dynamics of viscous plasmas with zero electrical resistance. As a consequence, we find that, if two axisymmetric plasma states are dynamically connected, then their total number of magnetic rings must be equal (the same as for the total numbers of magnetic blobs) and the corresponding infinitely many new invariants must coincide.

Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

NASA Astrophysics Data System (ADS)

Pizzolato, Nicola; Valenti, Davide; Adorno, Dominique Persano; Spagnolo, Bernardo

2009-09-01

The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.

Comparison of Multiple Molecular Dynamics Trajectories Calculated for the Drug-Resistant HIV-1 Integrase T66I/M154I Catalytic Domain

PubMed Central

Brigo, Alessandro; Lee, Keun Woo; Iurcu Mustata, Gabriela; Briggs, James M.

2005-01-01

HIV-1 integrase (IN) is an essential enzyme for the viral replication and an interesting target for the design of new pharmaceuticals for multidrug therapy of AIDS. Single and multiple mutations of IN at residues T66, S153, or M154 confer degrees of resistance to several inhibitors that prevent the enzyme from performing its normal strand transfer activity. Four different conformations of IN were chosen from a prior molecular dynamics (MD) simulation on the modeled IN T66I/M154I catalytic core domain as starting points for additional MD studies. The aim of this article is to understand the dynamic features that may play roles in the catalytic activity of the double mutant enzyme in the absence of any inhibitor. Moreover, we want to verify the influence of using different starting points on the MD trajectories and associated dynamical properties. By comparison of the trajectories obtained from these MD simulations we have demonstrated that the starting point does not affect the conformational space explored by this protein and that the time of the simulation is long enough to achieve convergence for this system. PMID:15764656

The Realization and Analysis of Capacitance Self Tracing (CST) Method for Wide Band Response Measurement of Carrier Type Dynamic Strain Amplifier

NASA Astrophysics Data System (ADS)

Kubodera, Shinji; Tanzawa, Tsutomu; Morisawa, Masayuki; Kiyohiro, Noriaki

Carrier type dynamic strain amplifiers are frequently used for stress measurement with strain gages. That is because the carrier type dynamic strain amplifier can conduct high precision measurement since it is highly resistant against hum noise from the power supply frequency in principle and is free from the thermoelectomotive force even if a metal contact is used in wiring to a Wheatstone bridge for measuring. A problem of the carrier type dynamic strain amplifier is generation of Capacitive component (hereinafter referred to as the C component) in an input cable connecting from the amplifier to the input sensor (Wheatstone bridge for measuring). The C component varies with cable length, cable materials, or ambient temperature change. The aforementioned changing adversely affects the stability of the amplifier. In this paper, we realize and analyze the method that increases the stability of amplifier by detecting, eliminating and self tracking the above C component constantly. Used carrier frequency at 12kHz and 28kHz. We made amplifiers with noise resistant and wide band frequency of measurement range and verified the theory of the Capacitance Self Tracing with the above amplifiers.

In situ determination of the static inductance and resistance of a plasma focus capacitor bank.

PubMed

Saw, S H; Lee, S; Roy, F; Chong, P L; Vengadeswaran, V; Sidik, A S M; Leong, Y W; Singh, A

2010-05-01

The static (unloaded) electrical parameters of a capacitor bank are of utmost importance for the purpose of modeling the system as a whole when the capacitor bank is discharged into its dynamic electromagnetic load. Using a physical short circuit across the electromagnetic load is usually technically difficult and is unnecessary. The discharge can be operated at the highest pressure permissible in order to minimize current sheet motion, thus simulating zero dynamic load, to enable bank parameters, static inductance L(0), and resistance r(0) to be obtained using lightly damped sinusoid equations given the bank capacitance C(0). However, for a plasma focus, even at the highest permissible pressure it is found that there is significant residual motion, so that the assumption of a zero dynamic load introduces unacceptable errors into the determination of the circuit parameters. To overcome this problem, the Lee model code is used to fit the computed current trace to the measured current waveform. Hence the dynamics is incorporated into the solution and the capacitor bank parameters are computed using the Lee model code, and more accurate static bank parameters are obtained.

In situ determination of the static inductance and resistance of a plasma focus capacitor bank

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

Saw, S. H.; Institute for Plasma Focus Studies, 32 Oakpark Drive, Chadstone, Victoria 3148; Lee, S.

2010-05-15

The static (unloaded) electrical parameters of a capacitor bank are of utmost importance for the purpose of modeling the system as a whole when the capacitor bank is discharged into its dynamic electromagnetic load. Using a physical short circuit across the electromagnetic load is usually technically difficult and is unnecessary. The discharge can be operated at the highest pressure permissible in order to minimize current sheet motion, thus simulating zero dynamic load, to enable bank parameters, static inductance L{sub 0}, and resistance r{sub 0} to be obtained using lightly damped sinusoid equations given the bank capacitance C{sub 0}. However, formore » a plasma focus, even at the highest permissible pressure it is found that there is significant residual motion, so that the assumption of a zero dynamic load introduces unacceptable errors into the determination of the circuit parameters. To overcome this problem, the Lee model code is used to fit the computed current trace to the measured current waveform. Hence the dynamics is incorporated into the solution and the capacitor bank parameters are computed using the Lee model code, and more accurate static bank parameters are obtained.« less

Bacterial charity work leads to population-wide resistance.

PubMed

Lee, Henry H; Molla, Michael N; Cantor, Charles R; Collins, James J

2010-09-02

Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population's less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.

Expanding the eco-evolutionary context of herbicide resistance research.

PubMed

Neve, Paul; Busi, Roberto; Renton, Michael; Vila-Aiub, Martin M

2014-09-01

The potential for human-driven evolution in economically and environmentally important organisms in medicine, agriculture and conservation management is now widely recognised. The evolution of herbicide resistance in weeds is a classic example of rapid adaptation in the face of human-mediated selection. Management strategies that aim to slow or prevent the evolution of herbicide resistance must be informed by an understanding of the ecological and evolutionary factors that drive selection in weed populations. Here, we argue for a greater focus on the ultimate causes of selection for resistance in herbicide resistance studies. The emerging fields of eco-evolutionary dynamics and applied evolutionary biology offer a means to achieve this goal and to consider herbicide resistance in a broader and sometimes novel context. Four relevant research questions are presented, which examine (i) the impact of herbicide dose on selection for resistance, (ii) plant fitness in herbicide resistance studies, (iii) the efficacy of herbicide rotations and mixtures and (iv) the impacts of gene flow on resistance evolution and spread. In all cases, fundamental ecology and evolution have the potential to offer new insights into herbicide resistance evolution and management. © 2014 Society of Chemical Industry.

Antiviral Drug-Resistance Typing Reveals Compartmentalization and Dynamics of Acyclovir-Resistant Herpes Simplex Virus Type-2 (HSV-2) in a Case of Neonatal Herpes.

PubMed

Bache, Manon; Andrei, Graciela; Bindl, Lutz; Bofferding, Léon; Bottu, Jean; Géron, Christine; Neuhäuser, Christoph; Gillemot, Sarah; Fiten, Pierre; Opdenakker, Ghislain; Snoeck, Robert

2014-06-01

A neonate suffering from herpes simplex virus type 2 disease with central nervous system involvement developed an early recurrence under acyclovir therapy. Isolates from the cerebrospinal fluid and skin lesions were acyclovir resistant, while viruses from blood and trachea were not. Acyclovir combined with foscavir followed by long-term suppressive acyclovir therapy supported normal neurological development. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Real time simulation using position sensing

NASA Technical Reports Server (NTRS)

Isbell, William B. (Inventor); Taylor, Jason A. (Inventor); Studor, George F. (Inventor); Womack, Robert W. (Inventor); Hilferty, Michael F. (Inventor); Bacon, Bruce R. (Inventor)

2000-01-01

An interactive exercise system including exercise equipment having a resistance system, a speed sensor, a controller that varies the resistance setting of the exercise equipment, and a playback device for playing pre-recorded video and audio. The controller, operating in conjunction with speed information from the speed sensor and terrain information from media table files, dynamically varies the resistance setting of the exercise equipment in order to simulate varying degrees of difficulty while the playback device concurrently plays back the video and audio to create the simulation that the user is exercising in a natural setting such as a real-world exercise course.

Multidrug-resistant tuberculosis (MDR-TB) in India: an attempt to link biosocial determinants.

PubMed

Atre, Sachin R; Mistry, Nerges F

2005-04-01

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a possible threat to global tuberculosis control efforts in recent years. It is a challenge not only from a public health point of view but also in the context of global economy, especially in the absence of treatment for MDR-TB at national-level programs in developing countries. Biological accounts are insufficient to understand the emergence and dynamics of drug resistance. This article focuses essentially on the need for a holistic perspective, linking biosocial determinants that would probably lead to better insights into MDR-TB control strategies.

Dynamics of change in rat arterial pressure under conditions of immobilization

NASA Technical Reports Server (NTRS)

Yumatov, Y. A.; Skotselyas, Y. G.; Ivanona, L. I.

1980-01-01

Emotional stress developed in immobilized rats was shown to be accompanied by changes in the regulation of arterial pressure and the frequency of cardiac contractions. A group of adapting rats displayed definite resistance to emotional stress, while a group of rats incapable of adapting to acute emotional stress died with characteristics of cardiovascular insufficiency. The mechanisms providing resistance to emotional stress in numerous conflict situations were analyzed.

About the influence of phase mixing process and current neutralization on the resistive sausage instability dynamics of a relativistic electron beam

NASA Astrophysics Data System (ADS)

Kolesnikov, E. K.; Manuilov, A. S.; Petrov, V. S.; Zelensky, A. G.

2018-05-01

The resistive sausage instability of the relativistic electron beam in dense gas-plasma medium in the case of the generation of equilibrium return plasma current is investigated. In this situation the eigenvalue equation of this instability is obtained. The stabilizing and destabilizing effects of the phase mixing and generation of the return plasma current respectively have been shown.

A fully covariant mean-field dynamo closure for numerical 3 + 1 resistive GRMHD

NASA Astrophysics Data System (ADS)

Bucciantini, N.; Del Zanna, L.

2013-01-01

The powerful high-energy phenomena typically encountered in astrophysics invariably involve physical engines, like neutron stars and black hole accretion discs, characterized by a combination of highly magnetized plasmas, strong gravitational fields and relativistic motions. In recent years, numerical schemes for general relativistic magnetohydrodynamics (GRMHD) have been developed to model the multidimensional dynamics of such systems, including the possibility of evolving space-time. Such schemes have been also extended beyond the ideal limit including the effects of resistivity, in an attempt to model dissipative physical processes acting on small scales (subgrid effects) over the global dynamics. Along the same lines, the magnetic field could be amplified by the presence of turbulent dynamo processes, as often invoked to explain the high values of magnetization required in accretion discs and neutron stars. Here we present, for the first time, a further extension to include the possibility of a mean-field dynamo action within the framework of numerical 3 + 1 (resistive) GRMHD. A fully covariant dynamo closure is proposed, in analogy with the classical theory, assuming a simple α-effect in the comoving frame. Its implementation into a finite-difference scheme for GRMHD in dynamical space-times (the x-echo code by Bucciantini & Del Zanna) is described, and a set of numerical test is presented and compared with analytical solutions wherever possible.

The model of fungal population dynamics affected by nystatin

NASA Astrophysics Data System (ADS)

Voychuk, Sergei I.; Gromozova, Elena N.; Sadovskiy, Mikhail G.

Fungal diseases are acute problems of the up-to-day medicine. Significant increase of resistance of microorganisms to the medically used antibiotics and a lack of new effective drugs follows in a growth of dosage of existing chemicals to solve the problem. Quite often such approach results in side effects on humans. Detailed study of fungi-antibiotic dynamics can identify new mechanisms and bring new ideas to overcome the microbial resistance with a lower dosage of antibiotics. In this study, the dynamics of the microbial population under antibiotic treatment was investigated. The effects of nystatin on the population of Saccharomyces cerevisiae yeasts were used as a model system. Nystatin effects were investigated both in liquid and solid media by viability tests. Dependence of nystatin action on osmotic gradient was evaluated in NaCl solutions. Influences of glucose and yeast extract were additionally analyzed. A "stepwise" pattern of the cell death caused by nystatin was the most intriguing. This pattern manifested in periodical changes of the stages of cell death against stages of resistance to the antibiotic. The mathematical model was proposed to describe cell-antibiotic interactions and nystatin viability effects in the liquid medium. The model implies that antibiotic ability to cause a cells death is significantly affected by the intracellular compounds, which came out of cells after their osmotic barriers were damaged

Dynamic Modeling and Interactive Performance of PARM: A Parallel Upper-Limb Rehabilitation Robot Using Impedance Control for Patients after Stroke.

PubMed

Guang, Hui; Ji, Linhong; Shi, Yingying; Misgeld, Berno J E

2018-01-01

The robot-assisted therapy has been demonstrated to be effective in the improvements of limb function and even activities of daily living for patients after stroke. This paper presents an interactive upper-limb rehabilitation robot with a parallel mechanism and an isometric screen embedded in the platform to display trajectories. In the dynamic modeling for impedance control, the effects of friction and inertia are reduced by introducing the principle of virtual work and derivative of Jacobian matrix. To achieve the assist-as-needed impedance control for arbitrary trajectories, the strategy based on orthogonal deviations is proposed. Simulations and experiments were performed to validate the dynamic modeling and impedance control. Besides, to investigate the influence of the impedance in practice, a subject participated in experiments and performed two types of movements with the robot, that is, rectilinear and circular movements, under four conditions, that is, with/without resistance or impedance, respectively. The results showed that the impedance and resistance affected both mean absolute error and standard deviation of movements and also demonstrated the significant differences between movements with/without impedance and resistance ( p < 0.001). Furthermore, the error patterns were discussed, which suggested that the impedance environment was capable of alleviating movement deviations by compensating the synergetic inadequacy between the shoulder and elbow joints.

Dynamic Modeling and Interactive Performance of PARM: A Parallel Upper-Limb Rehabilitation Robot Using Impedance Control for Patients after Stroke

PubMed Central

Shi, Yingying; Misgeld, Berno J. E.

2018-01-01

The robot-assisted therapy has been demonstrated to be effective in the improvements of limb function and even activities of daily living for patients after stroke. This paper presents an interactive upper-limb rehabilitation robot with a parallel mechanism and an isometric screen embedded in the platform to display trajectories. In the dynamic modeling for impedance control, the effects of friction and inertia are reduced by introducing the principle of virtual work and derivative of Jacobian matrix. To achieve the assist-as-needed impedance control for arbitrary trajectories, the strategy based on orthogonal deviations is proposed. Simulations and experiments were performed to validate the dynamic modeling and impedance control. Besides, to investigate the influence of the impedance in practice, a subject participated in experiments and performed two types of movements with the robot, that is, rectilinear and circular movements, under four conditions, that is, with/without resistance or impedance, respectively. The results showed that the impedance and resistance affected both mean absolute error and standard deviation of movements and also demonstrated the significant differences between movements with/without impedance and resistance (p < 0.001). Furthermore, the error patterns were discussed, which suggested that the impedance environment was capable of alleviating movement deviations by compensating the synergetic inadequacy between the shoulder and elbow joints. PMID:29850004

Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise.

PubMed

Camera, Donny M; Burniston, Jatin G; Pogson, Mark A; Smiles, William J; Hawley, John A

2017-12-01

It is generally accepted that muscle adaptation to resistance exercise (REX) training is underpinned by contraction-induced, increased rates of protein synthesis and dietary protein availability. By using dynamic proteome profiling (DPP), we investigated the contribution of both synthesis and breakdown to changes in abundance on a protein-by-protein basis in human skeletal muscle. Age-matched, overweight males consumed 9 d of a high-fat, low-carbohydrate diet during which time they either undertook 3 sessions of REX or performed no exercise. Precursor enrichment and the rate of incorporation of deuterium oxide into newly synthesized muscle proteins were determined by mass spectrometry. Ninety proteins were included in the DPP, with 28 proteins exhibiting significant responses to REX. The most common pattern of response was an increase in turnover, followed by an increase in abundance with no detectable increase in protein synthesis. Here, we provide novel evidence that demonstrates that the contribution of synthesis and breakdown to changes in protein abundance induced by REX differ on a protein-by-protein basis. We also highlight the importance of the degradation of individual muscle proteins after exercise in human skeletal muscle.-Camera, D. M., Burniston, J. G., Pogson, M. A., Smiles, W. J., Hawley, J. A. Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise. © FASEB.

Does freezing and dynamic flexing of frozen branches impact the cavitation resistance of Malus domestica and the Populus clone Walker?

PubMed

Christensen-Dalsgaard, Karen K; Tyree, Melvin T

2013-11-01

Frost damage to the xylem conduits of trees is a phenomenon of eco-physiological importance. It is often documented in terms of the percentage loss of conductivity (PLC), an indicator of air filling of the conduits. However, trees that refill their conduits in spring could be impacted more by damage to the conduits that reduce cavitation resistance, making them more susceptible to future drought events. We investigated whether ice formation, dynamic flexing of frozen branches or freeze-thaw events could reduce the cavitation resistance (cause "frost fatigue") in first-year shoots of apple (Malus domestica) and clonal hybrid cottonwood (Walker). Frost fatigue was measured in terms of P50 (the negative xylem pressure required to cause a 50 % loss of conductivity). All treatment groups showed significant frost fatigue, with the exception of the pre-flushed, constantly frozen poplar branches. The P50 following freeze treatments was approximately 50 % of the pre-freeze values. The effect tended to be greater in freeze-thawed branches. Dynamic bending of the branches had no effect on either PLC or P50. In three out of four cases, there was a significant correlation between P50 and PLC. Frost fatigue occurred in both apple and poplar, two unrelated species with different drought and frost tolerances, suggesting that it may be a widespread phenomenon that could impact the ecophysiology of temperate forests.

Novel Digital Features Discriminate Between Drought Resistant and Drought Sensitive Rice Under Controlled and Field Conditions.

PubMed

Duan, Lingfeng; Han, Jiwan; Guo, Zilong; Tu, Haifu; Yang, Peng; Zhang, Dong; Fan, Yuan; Chen, Guoxing; Xiong, Lizhong; Dai, Mingqiu; Williams, Kevin; Corke, Fiona; Doonan, John H; Yang, Wanneng

2018-01-01

Dynamic quantification of drought response is a key issue both for variety selection and for functional genetic study of rice drought resistance. Traditional assessment of drought resistance traits, such as stay-green and leaf-rolling, has utilized manual measurements, that are often subjective, error-prone, poorly quantified and time consuming. To relieve this phenotyping bottleneck, we demonstrate a feasible, robust and non-destructive method that dynamically quantifies response to drought, under both controlled and field conditions. Firstly, RGB images of individual rice plants at different growth points were analyzed to derive 4 features that were influenced by imposition of drought. These include a feature related to the ability to stay green, which we termed greenness plant area ratio (GPAR) and 3 shape descriptors [total plant area/bounding rectangle area ratio (TBR), perimeter area ratio (PAR) and total plant area/convex hull area ratio (TCR)]. Experiments showed that these 4 features were capable of discriminating reliably between drought resistant and drought sensitive accessions, and dynamically quantifying the drought response under controlled conditions across time (at either daily or half hourly time intervals). We compared the 3 shape descriptors and concluded that PAR was more robust and sensitive to leaf-rolling than the other shape descriptors. In addition, PAR and GPAR proved to be effective in quantification of drought response in the field. Moreover, the values obtained in field experiments using the collection of rice varieties were correlated with those derived from pot-based experiments. The general applicability of the algorithms is demonstrated by their ability to probe archival Miscanthus data previously collected on an independent platform. In conclusion, this image-based technology is robust providing a platform-independent tool for quantifying drought response that should be of general utility for breeding and functional genomics in future.

Identification of anaerobic threshold by analysis of heart rate variability during discontinuous dynamic and resistance exercise protocols in healthy older men.

PubMed

Simões, Rodrigo Polaquini; Castello-Simões, Viviane; Mendes, Renata Gonçalves; Archiza, Bruno; Dos Santos, Daniel Augusto; Bonjorno, José Carlos; de Oliveira, Claudio Ricardo; Catai, Aparecida Maria; Arena, Ross; Borghi-Silva, Audrey

2014-03-01

The purposes of this study were to determine anaerobic threshold (AT) during discontinuous dynamic and resistive exercise protocols by analysing of heart rate variability (HRV) and blood lactate (BL) in healthy elderly subjects and compare the cardiovascular, metabolic and autonomic variables obtained from these two forms of exercise. Fourteen elderly (70 ± 4 years) apparently healthy males underwent the following tests: (i) incremental ramp test on cycle ergometer, (ii) one repetition maximum (1RM) leg press at 45°, (iii) a discontinuous exercise test on a cycle ergometer (DET-C) protocol and (iv) a resistance exercise leg press (DET-L) protocol. Heart rate, blood pressure and BL were obtained during each increment of exercise intensity. No significant differences (P>0·05) were found between methods of AT determination (BL and HRV) nor the relative intensity corresponding to AT (30% of maximum intensity) between the types of exercise (DET-C and DET-L). Furthermore, no significant differences (P>0·05) were found between the DET-C and DET-L in relation to HRV, however, the DET-L provided higher values of systolic blood pressure and BL (P<0·05) from the intensity corresponding to AT. We conclude that HRV was effective in determination of AT, and the parasympathetic modulation responses obtained during dynamic and resistive exercise protocols were similar when compared at the same relative intensity. However, DET-L resulted in higher values of blood pressure and BL at workloads beyond AT. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Acute resistance exercise reduces blood pressure and vascular reactivity, and increases endothelium-dependent relaxation in spontaneously hypertensive rats.

PubMed

Faria, Thaís de Oliveira; Targueta, Gabriel Pelegrineti; Angeli, Jhuli Keli; Almeida, Edna Aparecida Silveira; Stefanon, Ivanita; Vassallo, Dalton Valentim; Lizardo, Juliana Hott de Fúcio

2010-09-01

The aim of the present study was to assess the effects of acute dynamic resistance exercise on resting blood pressure (BP) and on endothelial function of vascular bed of spontaneously hypertensive rats. Hemodynamic measurements were performed before and after acute dynamic resistance exercise in conscious animals. After exercise, the tail artery was cannulated for mean perfusion pressure with constant flow measurement and for performing concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) and dose-response curves to phenylephrine (PHE). PHE protocol was also repeated with damaged endothelium and after L-NAME and indomethacin perfusion on the tail. The maximal response (E(max)) and sensitivity (pD(2)) were evaluated to these drugs. Exercise reduced resting systolic and diastolic BP (Delta -79 +/- 1.8; -23 +/- 2.3 mmHg, respectively; P < 0.05). ACh-induced relaxation increased in the exercise group (pD(2) = 9.8 +/- 0.06, P < 0.05) when compared with control rats (pD(2) = 8.7 +/- 0.1). The E(max) to PHE with intact endothelium decreased following exercise condition (439 +/- 18 mmHg, P < 0.05) when compared with control rats (276 +/- 22 mmHg). This response was abolished after L-NAME and indomethacin administration. After damage of the endothelium, PHE responses were not significantly different between the groups; however, E(max) and pD(2) increased when compared with responses obtained with intact endothelium. The results demonstrated that acute dynamic resistance exercise decreased resting BP and reactivity to PHE and increased endothelium-dependent relaxation. Nitric oxide and vasodilators prostanoids appear to be involved in post-exercise endothelial and pressor responses.

Mitochondrial motility and vascular smooth muscle proliferation.

PubMed

Chalmers, Susan; Saunter, Christopher; Wilson, Calum; Coats, Paul; Girkin, John M; McCarron, John G

2012-12-01

Mitochondria are widely described as being highly dynamic and adaptable organelles, and their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behavior to the physiological function of cells is unclear and was studied in single myocytes and intact resistance-sized cerebral arteries. We hypothesized that mitochondrial dynamics is controlled by the proliferative status of the cells. High-speed fluorescence imaging of mitochondria in live vascular smooth muscle cells shows that the organelle undergoes significant reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are largely immobile structures, except in a small number of cells in which motility occurred. When proliferation of smooth muscle was encouraged in the intact resistance artery, in organ culture, the majority of mitochondria became motile and the majority of smooth muscle cells contained moving mitochondria. Significantly, restriction of mitochondrial motility using the fission blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and the intact resistance artery. These results show that mitochondria are adaptable and exist in intact tissue as both stationary and highly dynamic entities. This mitochondrial plasticity is an essential mechanism for the development of smooth muscle proliferation and therefore presents a novel therapeutic target against vascular disease.

Long-term 4D Geoelectrical Imaging of Moisture Dynamics in an Active Landslide

NASA Astrophysics Data System (ADS)

Uhlemann, S.; Chambers, J. E.; Wilkinson, P. B.; Maurer, H.; Meldrum, P.; Gunn, D.; Smith, A.; Dijkstra, T.

2016-12-01

Landslides are a major natural hazard, endangering communities and infrastructure worldwide. Mitigating landslide risk relies on understanding causes and triggering processes, which are often linked to moisture dynamics in slopes causing material softening and elevated pore water pressures. Geoelectrical monitoring is frequently applied to study landslide hydrology. However, its sensitivity to sensor movements has been a challenge for long-term studies on actively failing slopes. Although 2D data acquisition has previously been favoured, it provides limited resolution and relatively poor representation of important 3D landslide structures. We present a novel methodology to incorporate electrode movements into a time-lapse 3D inversion workflow, resulting in a virtually artefact-free time-series of resistivity models. Using temperature correction and laboratory hydro-geophysical relationships, resistivity models are translated into models of moisture content. The data span more than three years, enabling imaging of processes pre- and post landslide reactivation. In the two years before reactivation, the models showed surficial wetting and drying, drainage pathways, and deeper groundwater dynamics. During reactivation, exceptionally high moisture contents were imaged throughout the slope, which was confirmed by independent measurements. Preferential flow was imaged that stabilized parts of the landslide by diverting moisture, and thus dissipating pore pressures, from the slip surface. The results highlight that moisture levels obtained from resistivity monitoring may provide a better activity threshold than rainfall intensity. Based on this work, pro-active remediation measures could be designed and effective early-warning systems implemented. Eventually, resistivity monitoring that can account for moving electrodes may provide a new means for pro-active mitigation of landslide risk, especially for communities and critical infrastructure.

Silver Nanowire Transparent Conductive Films with High Uniformity Fabricated via a Dynamic Heating Method.

PubMed

Jia, Yonggao; Chen, Chao; Jia, Dan; Li, Shuxin; Ji, Shulin; Ye, Changhui

2016-04-20

The uniformity of the sheet resistance of transparent conductive films is one of the most important quality factors for touch panel applications. However, the uniformity of silver nanowire transparent conductive films is far inferior to that of indium-doped tin oxide (ITO). Herein, we report a dynamic heating method using infrared light to achieve silver nanowire transparent conductive films with high uniformity. This method can overcome the coffee ring effect during the drying process and suppress the aggregation of silver nanowires in the film. A nonuniformity factor of the sheet resistance of the as-prepared silver nanowire transparent conductive films could be as low as 6.7% at an average sheet resistance of 35 Ω/sq and a light transmittance of 95% (at 550 nm), comparable to that of high-quality ITO film in the market. In addition, a mechanical study shows that the sheet resistance of the films has little change after 5000 bending cycles, and the film could be used in touch panels for human-machine interactive input. The highly uniform and mechanically stable silver nanowire transparent conductive films meet the requirement for many significant applications and could play a key role in the display market in a near future.

A physics-based fractional order model and state of energy estimation for lithium ion batteries. Part I: Model development and observability analysis

NASA Astrophysics Data System (ADS)

Li, Xiaoyu; Fan, Guodong; Pan, Ke; Wei, Guo; Zhu, Chunbo; Rizzoni, Giorgio; Canova, Marcello

2017-11-01

The design of a lumped parameter battery model preserving physical meaning is especially desired by the automotive researchers and engineers due to the strong demand for battery system control, estimation, diagnosis and prognostics. In light of this, a novel simplified fractional order electrochemical model is developed for electric vehicle (EV) applications in this paper. In the model, a general fractional order transfer function is designed for the solid phase lithium ion diffusion approximation. The dynamic characteristics of the electrolyte concentration overpotential are approximated by a first-order resistance-capacitor transfer function in the electrolyte phase. The Ohmic resistances and electrochemical reaction kinetics resistance are simplified to a lumped Ohmic resistance parameter. Overall, the number of model parameters is reduced from 30 to 9, yet the accuracy of the model is still guaranteed. In order to address the dynamics of phase-change phenomenon in the active particle during charging and discharging, variable solid-state diffusivity is taken into consideration in the model. Also, the observability of the model is analyzed on two types of lithium ion batteries subsequently. Results show the fractional order model with variable solid-state diffusivity agrees very well with experimental data at various current input conditions and is suitable for electric vehicle applications.

Resistivity profile effects in numerical magnetohydrodynamic simulations of the reversed-field pinch

NASA Astrophysics Data System (ADS)

Sätherblom, H.-E.; Mazur, S.; Nordlund, P.

1996-12-01

The influence of the resistivity profile on reversed-field pinch (RFP) dynamics is investigated numerically using a three-dimensional resistive magnetohydrodynamic code. This investigation is motivated by experimental observations on the EXTRAP-T1 RFP (Nordlund P et al 1994 Int. Conf. Plasma Physics and Controlled Nuclear Fusion Research IAEA-CN-60/A6/C-P-6). Two cases with profiles mainly differing in the edge region, i.e. in the region outside the reversal surface, are simulated. It is found that increasing the resistivity in this region results in a factor of two increase in magnetic fluctuation energy and an equal amount in the fluctuation-induced electric field. In spite of this, the parallel current decreases in the edge region, resulting in a factor two reduction of the field reversal ratio. The dynamics become more irregular and the characteristic timescale is reduced. The final state is characterized by a higher loop voltage, slightly lower values of the total (fluctuating plus mean part) magnetic energy and the magnetic helicity, but almost unchanged Taylor relaxation ratio. The results indicate that the edge region can be important for RFP confinement since cooling of the plasma in this region can lead to an increased fluctuation level and degraded performance.

Smart wearable Kevlar-based safeguarding electronic textile with excellent sensing performance.

PubMed

Wang, Sheng; Xuan, Shouhu; Liu, Mei; Bai, Linfeng; Zhang, Shuaishuai; Sang, Min; Jiang, Wanquan; Gong, Xinglong

2017-03-29

A novel S-ST/MWCNT/Kevlar-based wearable electronic textile (WET) with enhanced safeguarding performance and force sensing ability was fabricated. Stab resistance performance tests under quasi-static and dynamic conditions show that the maximum resistance force and penetration impact energy for the WET are 18 N and 11.76 J, which represent a 90% and 50% increment with respect to the neat Kevlar, respectively. Dynamic impact resistance tests show that the WET absorbs all the impact energy. The maximum resistance force of the WET is 1052 N, which represents an improvement of about 190% with respect to neat Kevlar. With the incorporation of multi-walled carbon nanotubes (MWCNTs), the WET can achieve a stable electrical conductivity of ∼10 -2 S m -1 , and the conductivity is highly sensitive to external mechanic forces. Notably, the sensing fabric also exhibits an outstanding ability to detect and analyze external forces. In addition, it can be fixed at any position of the human body and exhibits an ideal monitoring performance. Because of its flexibility, high sensitivity to various types of deformations and excellent safeguarding performance, the WET has a strong potential for wearable monitoring devices that simultaneously provide body protection and monitor the movements of the human body under various conditions.

Effects of eletron heating on the current driven electrostatic ion cyclotron instability and plasma transport processes along auroral field lines

NASA Technical Reports Server (NTRS)

Ganguli, Supriya B.; Mitchell, Horace G.; Palmadesso, Peter J.

1988-01-01

Fluid simulations of the plasma along auroral field lines in the return current region have been performed. It is shown that the onset of electrostatic ion cyclotron (EIC) related anomalous resistivity and the consequent heating of electrons leads to a transverse ion temperature that is much higher than that produced by the current driven EIC instability (CDICI) alone. Two processes are presented for the enhancement of ion heating by anomalous resistivity. The anomalous resistivity associated with the turbulence is limited by electron heating, so that CDICI saturates at transverse temperature that is substantially higher than in the absence of resistivity. It is suggested that this process demonstrates a positive feedback loop in the interaction between CDICI, anomalous resistivity, and parallel large-scale dynamics in the topside ionosphere.

Relation Between Open Circuit Potential and Polarization Resistance with Rust and Corrosion Monitoring of Mild Steel

NASA Astrophysics Data System (ADS)

Choudhary, S.; Garg, A.; Mondal, K.

2016-07-01

The present work discusses continuous corrosion assessment from a unique correlation of open circuit potential (OCP) and linear polarization resistance with rust formation on mild steel after prolong exposure in 3.5% NaCl salt fog environment. The OCP measurement and linear polarization tests were carried out of the rusted samples only without the removal of rust. It also discusses the strong influence of the composition, fraction, and morphology of the rust layers with OCP and linear polarization resistance. The rust characterization was done after the measurement of OCP and linear polarization resistance of the rusted steel samples. Therefore, monitoring of both the OCP and linear polarization resistance of the rusted mild steels coupled with rust characterization could be used for easy and dynamic assessment of the nature of corrosion.

Dynamics of Nanoparticles in Entangled Polymer Solutions

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

Nath, Pooja; Mangal, Rahul; Kohle, Ferdinand

The mean square displacement < r 2 > of nanoparticle probes dispersed in simple isotropic liquids and in polymer solutions is interrogated using fluorescence correlation spectroscopy and single-particle tracking (SPT) experiments. Probe dynamics in different regimes of particle diameter (d), relative to characteristic polymer length scales, including the correlation length (ξ), the entanglement mesh size (a), and the radius of gyration (R g), are investigated. In simple fluids and for polymer solutions in which d >> R g, long-time particle dynamics obey random-walk statistics < r 2 >:t, with the bulk zero-shear viscosity of the polymer solution determining the frictionalmore » resistance to particle motion. In contrast, in polymer solutions with d < R g, polymer molecules in solution exert noncontinuum resistances to particle motion and nanoparticle probes appear to interact hydrodynamically only with a local fluid medium with effective drag comparable to that of a solution of polymer chain segments with sizes similar to those of the nanoparticle probes. Under these conditions, the nanoparticles exhibit orders of magnitude faster dynamics than those expected from continuum predictions based on the Stokes–Einstein relation. SPT measurements further show that when d > a, nanoparticle dynamics transition from diffusive to subdiffusive on long timescales, reminiscent of particle transport in a field with obstructions. This last finding is in stark contrast to the nanoparticle dynamics observed in entangled polymer melts, where X-ray photon correlation spectroscopy measurements reveal faster but hyperdiffusive dynamics. As a result, we analyze these results with the help of the hopping model for particle dynamics in polymers proposed by Cai et al. and, on that basis, discuss the physical origins of the local drag experienced by the nanoparticles in entangled polymer solutions.« less

Dynamics of Nanoparticles in Entangled Polymer Solutions

DOE PAGES

Nath, Pooja; Mangal, Rahul; Kohle, Ferdinand; ...

2017-12-01

The mean square displacement < r 2 > of nanoparticle probes dispersed in simple isotropic liquids and in polymer solutions is interrogated using fluorescence correlation spectroscopy and single-particle tracking (SPT) experiments. Probe dynamics in different regimes of particle diameter (d), relative to characteristic polymer length scales, including the correlation length (ξ), the entanglement mesh size (a), and the radius of gyration (R g), are investigated. In simple fluids and for polymer solutions in which d >> R g, long-time particle dynamics obey random-walk statistics < r 2 >:t, with the bulk zero-shear viscosity of the polymer solution determining the frictionalmore » resistance to particle motion. In contrast, in polymer solutions with d < R g, polymer molecules in solution exert noncontinuum resistances to particle motion and nanoparticle probes appear to interact hydrodynamically only with a local fluid medium with effective drag comparable to that of a solution of polymer chain segments with sizes similar to those of the nanoparticle probes. Under these conditions, the nanoparticles exhibit orders of magnitude faster dynamics than those expected from continuum predictions based on the Stokes–Einstein relation. SPT measurements further show that when d > a, nanoparticle dynamics transition from diffusive to subdiffusive on long timescales, reminiscent of particle transport in a field with obstructions. This last finding is in stark contrast to the nanoparticle dynamics observed in entangled polymer melts, where X-ray photon correlation spectroscopy measurements reveal faster but hyperdiffusive dynamics. As a result, we analyze these results with the help of the hopping model for particle dynamics in polymers proposed by Cai et al. and, on that basis, discuss the physical origins of the local drag experienced by the nanoparticles in entangled polymer solutions.« less

Conceptual Design and Dynamics Testing and Modeling of a Mars Tumbleweed Rover

NASA Technical Reports Server (NTRS)

Calhoun Philip C.; Harris, Steven B.; Raiszadeh, Behzad; Zaleski, Kristina D.

2005-01-01

The NASA Langley Research Center has been developing a novel concept for a Mars planetary rover called the Mars Tumbleweed. This concept utilizes the wind to propel the rover along the Mars surface, bringing it the potential to cover vast distances not possible with current Mars rover technology. This vehicle, in its deployed configuration, must be large and lightweight to provide the ratio of drag force to rolling resistance necessary to initiate motion from rest on the Mars surface. One Tumbleweed design concept that satisfies these considerations is called the Eggbeater-Dandelion. This paper describes the basic design considerations and a proposed dynamics model of the concept for use in simulation studies. It includes a summary of rolling/bouncing dynamics tests that used videogrammetry to better understand, characterize, and validate the dynamics model assumptions, especially the effective rolling resistance in bouncing/rolling dynamic conditions. The dynamics test used cameras to capture the motion of 32 targets affixed to a test article s outer structure. Proper placement of the cameras and alignment of their respective fields of view provided adequate image resolution of multiple targets along the trajectory as the test article proceeded down the ramp. Image processing of the frames from multiple cameras was used to determine the target positions. Position data from a set of these test runs was compared with results of a three dimensional, flexible dynamics model. Model input parameters were adjusted to match the test data for runs conducted. This process presented herein provided the means to characterize the dynamics and validate the simulation of the Eggbeater-Dandelion concept. The simulation model was used to demonstrate full scale Tumbleweed motion from a stationary condition on a flat-sloped terrain using representative Mars environment parameters.

HIV-1 resistance dynamics in patients failing dolutegravir maintenance monotherapy.

PubMed

Wijting, Ingeborg E A; Lungu, Cynthia; Rijnders, Bart J A; van der Ende, Marchina E; Pham, Hanh T; Mesplede, Thibault; Pas, Suzan D; Voermans, Jolanda J C; Schuurman, Rob; van de Vijver, David A M C; Boers, Patrick H M; Gruters, Rob A; Boucher, Charles A B; van Kampen, Jeroen J A

2018-03-29

A high genetic resistance barrier to the integrase-strand-transfer-inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI-resistance-associated-mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virological failure (VF) observed in the randomized dolutegravir maintenance monotherapy study (DOMONO, NCT02401828). From ten patients with VF plasma samples prior to start cART and during VF were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3'- LTR, and the 3'-PPT. Median HIV-RNA (IQR) at VF was 3,490 (1,440-4,990) c/mL. INSTI-RAMs were detected in 4/10 patients (S230R, R263K, N155H, E92Q+N155H) and in 4/10 patients no INSTI-RAMs were detected (2/10 patients integrase sequencing was unsuccessful). The time-to-VF ranged from 4 weeks to 72 weeks. In one patient, mutations developed in the highly conserved 3'-PPT. No changes in the terminal bases of the 3'-LTR were observed. The genetic barrier to resistance is too low to justify dolutegravir maintenance monotherapy as single INSTI-RAMs are sufficient to cause VF. The large variation in time-to-VF suggests that stochastic reactivation of a pre-existing provirus containing a single INSTI-RAM is the mechanism for failure. Changes in the 3'-PPT point to a new dolutegravir resistance mechanism in vivo.

Insulin Signaling in Type 2 Diabetes

PubMed Central

Brännmark, Cecilia; Nyman, Elin; Fagerholm, Siri; Bergenholm, Linnéa; Ekstrand, Eva-Maria; Cedersund, Gunnar; Strålfors, Peter

2013-01-01

Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems level mechanistic understanding of insulin resistance, using systems wide and internally consistent data from human adipocytes. Based on quantitative steady-state and dynamic time course data on signaling intermediaries, normally and in diabetes, we developed a dynamic mathematical model of insulin signaling. The model structure and parameters are identical in the normal and diabetic states of the model, except for three parameters that change in diabetes: (i) reduced concentration of insulin receptor, (ii) reduced concentration of insulin-regulated glucose transporter GLUT4, and (iii) changed feedback from mammalian target of rapamycin in complex with raptor (mTORC1). Modeling reveals that at the core of insulin resistance in human adipocytes is attenuation of a positive feedback from mTORC1 to the insulin receptor substrate-1, which explains reduced sensitivity and signal strength throughout the signaling network. Model simulations with inhibition of mTORC1 are comparable with experimental data on inhibition of mTORC1 using rapamycin in human adipocytes. We demonstrate the potential of the model for identification of drug targets, e.g. increasing the feedback restores insulin signaling, both at the cellular level and, using a multilevel model, at the whole body level. Our findings suggest that insulin resistance in an expanded adipose tissue results from cell growth restriction to prevent cell necrosis. PMID:23400783

Determination of charge transfer resistance and capacitance of microbial fuel cell through a transient response analysis of cell voltage.

PubMed

Ha, Phuc Thi; Moon, Hyunsoo; Kim, Byung Hong; Ng, How Yong; Chang, In Seop

2010-03-15

An alternative method for determining the charge transfer resistance and double-layer capacitance of microbial fuel cells (MFCs), easily implemented without a potentiostat, was developed. A dynamic model with two parameters, the charge transfer resistance and double-layer capacitance of electrodes, was derived from a linear differential equation to depict the current generation with respect to activation overvoltage. This model was then used to fit the transient cell voltage response to the current step change during the continuous operation of a flat-plate type MFC fed with acetate. Variations of the charge transfer resistance and the capacitance value with respect to the MFC design conditions (biocatalyst existence and electrode area) and operating parameters (acetate concentration and buffer strength in the catholyte) were then determined to elucidate the validity of the proposed method. This model was able to describe the dynamic behavior of the MFC during current change in the activation loss region; having an R(2) value of over 0.99 in most tests. Variations of the charge transfer resistance value (thousands of Omega) according to the change of the design factors and operational factors were well-correlated with the corresponding MFC performances. However, though the capacitance values (approximately 0.02 F) reflected the expected trend according to the electrode area change and catalyst property, they did not show significant variation with changes in either the acetate concentration or buffer strength. (c) 2009 Elsevier B.V. All rights reserved.

Objectives, Outlines, and Preparation for the Resist Tubule Space Experiment to Understand the Mechanism of Gravity Resistance in Plants

NASA Astrophysics Data System (ADS)

Hoson, Takayuki; Akamatsu, Haruhiko; Soga, Kouichi; Wakabayashi, Kazuyuki; Hashimoto, Hirofumi; Yamashita, Masamichi; Hasegawa, Katsuya; Yano, Sachiko; Omori, Katsunori; Ishioka, Noriaki; Matsumoto, Shohei; Kasahara, Haruo; Shimazu, Toru; A. Baba, Shoji; Hashimoto, Takashi

Gravity resistance is a principal graviresponse in plants. In resistance to hypergravity, the gravity signal may be perceived by the mechanoreceptors located on the plasma membrane, and then transformed and transduced via the structural continuum or physiological continuity of cortical microtubules-plasma membrane-cell wall, leading to an increase in the cell wall rigidity as the final response. The Resist Tubule experiment, which will be conducted in the Kibo Module on the International Space Station, aims to confirm that this hypothesis is applicable to resistance to 1 G gravity. There are two major objectives in the Resist Tubule experiment. One is to quantify the contributions of cortical microtubules to gravity resistance using Arabidopsis tubulin mutants with different degrees of defects. Another objective is to analyze the modifications to dynamics of cortical microtubules and membrane rafts under microgravity conditions on-site by observing green fluorescent protein (GFP)-expressing Arabidopsis lines with the fluorescence microscope in the Kibo. We have selected suitable mutants, developed necessary hardware, and fixed operation procedure for the experiment.

Estimation of composite hydraulic resistance in ice-covered alluvial streams

NASA Astrophysics Data System (ADS)

Ghareh Aghaji Zare, Soheil; Moore, Stephanie A.; Rennie, Colin D.; Seidou, Ousmane; Ahmari, Habib; Malenchak, Jarrod

2016-02-01

Formation, propagation, and recession of ice cover introduce a dynamic boundary layer to the top of rivers during northern winters. Ice cover affects water velocity magnitude and distribution, water level and consequently conveyance capacity of the river. In this research, total resistance, i.e., "composite resistance," is studied for a 4 month period including stable ice cover, breakup, and open water stages in Lower Nelson River (LNR), northern Manitoba, Canada. Flow and ice characteristics such as water velocity and depth and ice thickness and condition were measured continuously using acoustic techniques. An Acoustic Doppler Current Profiler (ADCP) and Shallow Water Ice Profiling Sonar (SWIPS) were installed simultaneously on a bottom mount and deployed for this purpose. Total resistance to the flow and boundary roughness are estimated using measured bulk hydraulic parameters. A novel method is developed to calculate composite resistance directly from measured under ice velocity profiles. The results of this method are compared to the measured total resistance and to the calculated composite resistance using formulae available in literature. The new technique is demonstrated to compare favorably to measured total resistance and to outperform previously available methods.

Thickened boundary layer theory for air film drag reduction on a van body surface

NASA Astrophysics Data System (ADS)

Xie, Xiaopeng; Cao, Lifeng; Huang, Heng

2018-05-01

To elucidate drag reduction mechanism on a van body surface under air film condition, a thickened boundary layer theory was proposed and a frictional resistance calculation model of the van body surface was established. The frictional resistance on the van body surface was calculated with different parameters of air film thickness. In addition, the frictional resistance of the van body surface under the air film condition was analyzed by computational fluid dynamics (CFD) simulation and different air film states that influenced the friction resistance on the van body surface were discussed. As supported by the CFD simulation results, the thickened boundary layer theory may provide reference for practical application of air film drag reduction on a van body surface.

Modal analysis and dynamic stresses for acoustically excited shuttle insulation tiles

NASA Technical Reports Server (NTRS)

Ojalvo, I. U.; Ogilvie, P. L.

1975-01-01

Improvements and extensions to the RESIST computer program developed for determining the normalized modal stress response of shuttle insulation tiles are described. The new version of RESIST can accommodate primary structure panels with closed-cell stringers, in addition to the capability for treating open-cell stringers. In addition, the present version of RESIST numerically solves vibration problems several times faster than its predecessor. A new digital computer program, titled ARREST (Acoustic Response of Reusable Shuttle Tiles) is also described. Starting with modal information contained on output tapes from RESIST computer runs, ARREST determines RMS stresses, deflections and accelerations of shuttle panels with reusable surface insulation tiles. Both programs are applicable to stringer stiffened structural panels with or without reusable surface insulation titles.

Effects of the resistivity profile on the formation of a reversed configuration and single helicity states in compressible simulations of the reversed-field pinch

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

Onofri, M.; Malara, F.

2013-10-15

Compressible magnetohydrodynamics simulations of the reversed-field pinch (RFP) are presented. Previous simulations of the RFP, including density and pressure evolution, showed that a stationary state with a reversed toroidal magnetic field could not be obtained, contrary to the results produced with numerical codes neglecting density and pressure dynamics. The simulations described in the present paper show that including density and pressure evolution, a stationary RFP configuration can be obtained if the resistivity has a radial profile steeply increasing close to the wall. Such resistivity profile is more realistic than a uniform resistivity, since the temperature at the wall is lowermore » than in the plasma core.« less

PATHOPHYSIOLOGICAN AND CLINICAL ASSESSMENT OF CHANGES OF ERYTHROCYTE RESISTANCE TO SAPONIN IN THE PROCESS OF ROENTGEN THERAPY (in Russian)

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

Krylov, A.A.

1961-04-01

In 40 patients undergoing roentgen therapy dynamic studies were made concerning the resistance of erythrocytes to saponin. A method of kinelysis was employed with a Soviet photoelectric colorimeter FEK-M. In the majority of patients subject to deep roentgen therapy there was noted a considerable rise of erythrocyte resistance to saponin, which is considered as a manifestation of compensatory mechanisms. A rapid decline of the resistance ("saponin disruption'') was preceded, as a ruls, by radiation toxemia and served as a signal of the necessity of repeated blood transfusions. The technique referred to is recommended as an objective index of the statemore » of regulatory mechanisms in the process of irradiation. (auth)« less

HIV Genetic Diversity and Drug Resistance

PubMed Central

Santos, André F.; Soares, Marcelo A.

2010-01-01

Most of the current knowledge on antiretroviral (ARV) drug development and resistance is based on the study of subtype B of HIV-1, which only accounts for 10% of the worldwide HIV infections. Cumulative evidence has emerged that different HIV types, groups and subtypes harbor distinct biological properties, including the response and susceptibility to ARV. Recent laboratory and clinical data highlighting such disparities are summarized in this review. Variations in drug susceptibility, in the emergence and selection of specific drug resistance mutations, in viral replicative capacity and in the dynamics of resistance acquisition under ARV selective pressure are discussed. Clinical responses to ARV therapy and associated confounding factors are also analyzed in the context of infections by distinct HIV genetic variants. PMID:21994646

Four-probe electrical-transport measurements on single indium tin oxide nanowires between 1.5 and 300 K

NASA Astrophysics Data System (ADS)

Chiu, Shao-Pin; Chung, Hui-Fang; Lin, Yong-Han; Kai, Ji-Jung; Chen, Fu-Rong; Lin, Juhn-Jong

2009-03-01

Single-crystalline indium tin oxide (ITO) nanowires (NWs) were grown by the standard thermal evaporation method. The as-grown NWs were typically 100-300 nm in diameter and a few µm long. Four-probe submicron Ti/Au electrodes on individual NWs were fabricated by the electron-beam lithography technique. The resistivities of several single NWs have been measured from 300 down to 1.5 K. The results indicate that the as-grown ITO NWs are metallic, but disordered. The overall temperature behavior of resistivity can be described by the Bloch-Grüneisen law plus a low-temperature correction due to the scattering of electrons off dynamic point defects. This observation suggests the existence of numerous dynamic point defects in as-grown ITO NWs.

Adaptive backstepping control of train systems with traction/braking dynamics and uncertain resistive forces

NASA Astrophysics Data System (ADS)

Song, Qi; Song, Y. D.; Cai, Wenchuan

2011-09-01

Although backstepping control design approach has been widely utilised in many practical systems, little effort has been made in applying this useful method to train systems. The main purpose of this paper is to apply this popular control design technique to speed and position tracking control of high-speed trains. By integrating adaptive control with backstepping control, we develop a control scheme that is able to address not only the traction and braking dynamics ignored in most existing methods, but also the uncertain friction and aerodynamic drag forces arisen from uncertain resistance coefficients. As such, the resultant control algorithms are able to achieve high precision train position and speed tracking under varying operation railway conditions, as validated by theoretical analysis and numerical simulations.

SRM Internal Flow Tests and Computational Fluid Dynamic Analysis. Volume 3; Titan, ASRM, and Subscale Motor Analyses

NASA Technical Reports Server (NTRS)

1995-01-01

A computational fluid dynamics (CFD) analysis has been performed on the aft slot region of the Titan 4 Solid Rocket Motor Upgrade (SRMU). This analysis was performed in conjunction with MSFC structural modeling of the propellant grain to determine if the flow field induced stresses would adversely alter the propellant geometry to the extent of causing motor failure. The results of the coupled CFD/stress analysis have shown that there is a continual increase of flow field resistance at the aft slot due to the aft segment propellant grain being progressively moved radially toward the centerline of the motor port. This 'bootstrapping' effect between grain radial movement and internal flow resistance is conducive to causing a rapid motor failure.

Anisotropic Josephson-vortex dynamics in layered organic superconductors

NASA Astrophysics Data System (ADS)

Yasuzuka, S.; Uji, S.; Satsukawa, H.; Kimata, M.; Terashima, T.; Koga, H.; Yamamura, Y.; Saito, K.; Akutsu, H.; Yamada, J.

2010-06-01

To study the anisotropic Josephson-vortex dynamics in the d-wave superconductors, the interplane resistance has been measured on layered organic superconductors κ-(ET)2Cu(NCS)2 and β-(BDA-TTP)2SbF6 under magnetic fields precisely parallel to the conducting planes. For κ-(ET)2Cu(NCS)2, in-plane angular dependence of the Josephson-vortex flow resistance is mainly described by the fourfold symmetry and dip structures appear when the magnetic field is applied parallel to the b- and c-axes. The obtained results have a relation to the d-wave superconducting gap symmetry. However, the absence of in-plane fourfold anisotropy was found for β-(BDA-TTP)2SbF6. The different anisotropic behavior is discussed in terms of the interlayer coupling strength.

Typical use of inverse dynamics in perceiving motion in autistic adults: Exploring computational principles of perception and action.

PubMed

Takamuku, Shinya; Forbes, Paul A G; Hamilton, Antonia F de C; Gomi, Hiroaki

2018-05-07

There is increasing evidence for motor difficulties in many people with autism spectrum condition (ASC). These difficulties could be linked to differences in the use of internal models which represent relations between motions and forces/efforts. The use of these internal models may be dependent on the cerebellum which has been shown to be abnormal in autism. Several studies have examined internal computations of forward dynamics (motion from force information) in autism, but few have tested the inverse dynamics computation, that is, the determination of force-related information from motion information. Here, we examined this ability in autistic adults by measuring two perceptual biases which depend on the inverse computation. First, we asked participants whether they experienced a feeling of resistance when moving a delayed cursor, which corresponds to the inertial force of the cursor implied by its motion-both typical and ASC participants reported similar feelings of resistance. Second, participants completed a psychophysical task in which they judged the velocity of a moving hand with or without a visual cue implying inertial force. Both typical and ASC participants perceived the hand moving with the inertial cue to be slower than the hand without it. In both cases, the magnitude of the effects did not differ between the two groups. Our results suggest that the neural systems engaged in the inverse dynamics computation are preserved in ASC, at least in the observed conditions. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. We tested the ability to estimate force information from motion information, which arises from a specific "inverse dynamics" computation. Autistic adults and a matched control group reported feeling a resistive sensation when moving a delayed cursor and also judged a moving hand to be slower when it was pulling a load. These findings both suggest that the ability to estimate force information from motion information is intact in autism. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

What you feel is what you see: inverse dynamics estimation underlies the resistive sensation of a delayed cursor.

PubMed

Takamuku, Shinya; Gomi, Hiroaki

2015-07-22

How our central nervous system (CNS) learns and exploits relationships between force and motion is a fundamental issue in computational neuroscience. While several lines of evidence have suggested that the CNS predicts motion states and signals from motor commands for control and perception (forward dynamics), it remains controversial whether it also performs the 'inverse' computation, i.e. the estimation of force from motion (inverse dynamics). Here, we show that the resistive sensation we experience while moving a delayed cursor, perceived purely from the change in visual motion, provides evidence of the inverse computation. To clearly specify the computational process underlying the sensation, we systematically varied the visual feedback and examined its effect on the strength of the sensation. In contrast to the prevailing theory that sensory prediction errors modulate our perception, the sensation did not correlate with errors in cursor motion due to the delay. Instead, it correlated with the amount of exposure to the forward acceleration of the cursor. This indicates that the delayed cursor is interpreted as a mechanical load, and the sensation represents its visually implied reaction force. Namely, the CNS automatically computes inverse dynamics, using visually detected motions, to monitor the dynamic forces involved in our actions. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

In-vitro development of a temporal abutment screw to protect osseointegration in immediate loaded implants

PubMed Central

2015-01-01

PURPOSE In this study, a temporal abutment fixation screw, designed to fracture in a controlled way upon application of an occlusal force sufficient to produce critical micromotion was developed. The purpose of the screw was to protect the osseointegration of immediate loaded single implants. MATERIALS AND METHODS Seven different screw prototypes were examined by fixing titanium abutments to 112 Mozo-Grau external hexagon implants (MG Osseous®; Mozo-Grau, S.A., Valladolid, Spain). Fracture strength was tested at 30° in two subgroups per screw: one under dynamic loading and the other without prior dynamic loading. Dynamic loading was performed in a single-axis chewing simulator using 150,000 load cycles at 50 N. After normal distribution of obtained data was verified by Kolmogorov-Smirnov test, fracture resistance between samples submitted and not submitted to dynamic loading was compared by the use of Student's t-test. Comparison of fracture resistance among different screw designs was performed by the use of one-way analysis of variance. Confidence interval was set at 95%. RESULTS Fractures occurred in all screws, allowing easy retrieval. Screw Prototypes 2, 5 and 6 failed during dynamic loading and exhibited statistically significant differences from the other prototypes. CONCLUSION Prototypes 2, 5 and 6 may offer a useful protective mechanism during occlusal overload in immediate loaded implants. PMID:25932315

Threshold virus dynamics with impulsive antiretroviral drug effects

PubMed Central

Lou, Jie; Lou, Yijun; Wu, Jianhong

2013-01-01

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible. PMID:21987085

Origin of the glass-like dynamics in molecular metals κ-(BEDT-TTF)2X: implications from fluctuation spectroscopy and ab initio calculations

NASA Astrophysics Data System (ADS)

Müller, Jens; Hartmann, Benedikt; Rommel, Robert; Brandenburg, Jens; Winter, Stephen M.; Schlueter, John A.

2015-08-01

We have studied the low-frequency dynamics of the charge carriers in different organic charge-transfer salts κ-(BEDT-TTF)2X with polymeric anions X by using resistance noise spectroscopy. Our aim is to investigate the structural, glass-like transition caused by the conformational degrees of freedom of the BEDT-TTF molecules’ terminal ethylene groups. Although of fundamental importance for studies of the electronic ground-state properties, the phenomenology of the glassy dynamics has been minimally investigated and its origin is not understood. Our systematic studies of fluctuation spectroscopy of various different compounds reveal a universal, pronounced maximum in the resistance noise power spectral density related to the glass transition. The energy scale of this process can be identified with the activation energy of the glass-like ethylene endgroup structural dynamics as determined from thermodynamic and NMR measurements. For the first time for this class of ‘plastic crystals’, we report a typical glassy property of the relaxation time, namely a Vogel-Fulcher-Tammann law, and are able to determine the degree of fragility of the glassy system. Supporting ab initio calculations provide an explanation for the origin and phenomenology of the glassy dynamics in different systems in terms of a simple two-level model, where the relevant energy scales are determined by the coupling of the ethylene endgroups to the anions.

Haptic control of a pneumatic muscle actuator to provide resistance for simulated isokinetic exercise; part II: control development and testing.

PubMed

Hall, Kara L; Phillips, Chandler A; Reynolds, David B; Mohler, Stanley R; Rogers, Dana B; Neidhard-Doll, Amy T

2015-01-01

Pneumatic muscle actuators (PMAs) have a high power to weight ratio and possess unique characteristics which make them ideal actuators for applications involving human interaction. PMAs are difficult to control due to nonlinear dynamics, presenting challenges in system implementation. Despite these challenges, PMAs have great potential as a source of resistance for strength training and rehabilitation. The objective of this work was to control a PMA for use in isokinetic exercise, potentially benefiting anyone in need of optimal strength training through a joint's range of motion. The controller, based on an inverse three-element phenomenological model and adaptive nonlinear control, allows the system to operate as a type of haptic device. A human quadriceps dynamic simulator was developed (as described in Part I of this work) so that control effectiveness and accommodation could be tested prior to human implementation. Tracking error results indicate that the control system is effective at producing PMA displacement and resistance necessary for a scaled, simulated neuromuscular actuator to maintain low-velocity isokinetic movement during simulated concentric and eccentric knee extension.

Corrosion Resistant FBG-Based Quasi-Distributed Sensor for Crude Oil Tank Dynamic Temperature Profile Monitoring

PubMed Central

da Silva Marques, Rogério; Prado, Adilson Ribeiro; da Costa Antunes, Paulo Fernando; de Brito André, Paulo Sérgio; Ribeiro, Moisés R. N.; Frizera-Neto, Anselmo; Pontes, Maria José

2015-01-01

This article presents a corrosion resistant, maneuverable, and intrinsically safe fiber Bragg grating (FBG)-based temperature optical sensor. Temperature monitoring is a critical activity for the oil and gas industry. It typically involves acquiring the desired parameters in a hazardous and corrosive environment. The use of polytetrafluoroethylene (PTFE) was proposed as a means of simultaneously isolating the optical fiber from the corrosive environment and avoiding undesirable mechanical tensions on the FBGs. The presented sensor head is based on multiple FBGs inscribed in a lengthy single mode fiber. The sensor presents an average thermal sensitivity of 8.82 ± 0.09 pm/°C, resulting in a typical temperature resolution of ~0.1 °C and an average time constant value of 6.25 ± 0.08 s. Corrosion and degradation resistance were verified by infrared spectroscopy and scanning electron microscopy during 90 days exposure to high salinity crude oil samples. The developed sensor was tested in a field pilot test, mimicking the operation of an inland crude tank, demonstrating its abilities to dynamically monitor temperature profile. PMID:26690166

Corrosion Resistant FBG-Based Quasi-Distributed Sensor for Crude Oil Tank Dynamic Temperature Profile Monitoring.

PubMed

Marques, Rogério da Silva; Prado, Adilson Ribeiro; Antunes, Paulo Fernando da Costa; André, Paulo Sérgio de Brito; Ribeiro, Moisés R N; Frizera-Neto, Anselmo; Pontes, Maria José

2015-12-05

This article presents a corrosion resistant, maneuverable, and intrinsically safe fiber Bragg grating (FBG)-based temperature optical sensor. Temperature monitoring is a critical activity for the oil and gas industry. It typically involves acquiring the desired parameters in a hazardous and corrosive environment. The use of polytetrafluoroethylene (PTFE) was proposed as a means of simultaneously isolating the optical fiber from the corrosive environment and avoiding undesirable mechanical tensions on the FBGs. The presented sensor head is based on multiple FBGs inscribed in a lengthy single mode fiber. The sensor presents an average thermal sensitivity of 8.82 ± 0.09 pm/°C, resulting in a typical temperature resolution of ~0.1 °C and an average time constant value of 6.25 ± 0.08 s. Corrosion and degradation resistance were verified by infrared spectroscopy and scanning electron microscopy during 90 days exposure to high salinity crude oil samples. The developed sensor was tested in a field pilot test, mimicking the operation of an inland crude tank, demonstrating its abilities to dynamically monitor temperature profile.

Discovery of thalicthuberine as a novel antimitotic agent from nature that disrupts microtubule dynamics and induces apoptosis in prostate cancer cells

PubMed Central

2018-01-01

ABSTRACT We report for the first time the mechanism of action of the natural product thalicthuberine (TH) in prostate and cervical cancer cells. TH induced a strong accumulation of LNCaP cells in mitosis, severe mitotic spindle defects, and asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied by cell death through apoptosis. However, unlike microtubule-binding drugs (vinblastine and paclitaxel), TH did not directly inhibit tubulin polymerization when tested in a cell-free system, whereas it reduced cellular microtubule polymer mass in LNCaP cells. This suggests that TH indirectly targets microtubule dynamics through inhibition of a critical regulator or tubulin-associated protein. Furthermore, TH is not a major substrate for P-glycoprotein (Pgp), which is responsible for multidrug resistance in numerous cancers, providing a rationale to further study TH in cancers with Pgp-mediated treatment resistance. The identification of TH's molecular target in future studies will be of great value to the development of TH as potential treatment of multidrug-resistant tumors. PMID:28749250

Self-Healable and Cold-Resistant Supercapacitor Based on a Multifunctional Hydrogel Electrolyte.

PubMed

Tao, Feng; Qin, Liming; Wang, Zhikui; Pan, Qinmin

2017-05-10

Excellent self-healability and cold resistance are attractive properties for a portable/wearable energy-storage device. However, achieving the features is fundamentally dependent on an intrinsically self-healable electrolyte with high ionic conduction at low temperature. Here we report such a hydrogel electrolyte comprising sodium alginate cross-linked by dynamic catechol-borate ester bonding. Since its dynamically cross-linked alginate network can tolerate high-content inorganic salts, the electrolyte possesses excellent healing efficiency/cyclability but also high ionic conduction at both room temperature and low temperature. A supercapacitor with the multifunctional hydrogel electrolyte completely restores its capacitive properties even after breaking/healing for 10 cycles without external stimulus. At a low temperature of -10 °C, the capacitor is even able to maintain at least 80% of its room-temperature capacitance. Our investigations offer a strategy to assemble self-healable and cold-resistant energy storage devices by using a multifunctional hydrogel electrolyte with rationally designed polymeric networks, which has potential application in portable/wearable electronics, intelligent apparel or flexible robot, and so on.

Resistance Elasticity of Antibiotic Demand in Intensive Care.

PubMed

Heister, Thomas; Hagist, Christian; Kaier, Klaus

2017-07-01

The emergence and spread of antimicrobial resistance (AMR) is still an unresolved problem worldwide. In intensive care units (ICUs), first-line antibiotic therapy is highly standardized and widely empiric while treatment failure because of AMR often has severe consequences. Simultaneously, there is a limited number of reserve antibiotics, whose prices and/or side effects are substantially higher than first-line therapy. This paper explores the implications of resistance-induced substitution effects in ICUs. The extent of such substitution effects is shown in a dynamic fixed effect regression analysis using a panel of 66 German ICUs with monthly antibiotic use and resistance data between 2001 and 2012. Our findings support the hypothesis that demand for reserve antibiotics substantially increases when resistance towards first-line agents rises. For some analyses the lagged effect of resistance is also significant, supporting the conjecture that part of the substitution effect is caused by physicians changing antibiotic choices in empiric treatment by adapting their resistance expectation to new information on resistance prevalence. The available information about resistance rates allows physicians to efficiently balance the trade-off between exacerbating resistance and ensuring treatment success. However, resistance-induced substitution effects are not free of charge. These effects should be considered an indirect burden of AMR. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

FEM Simulation of Small Wind Power Generating System Using PMSG

NASA Astrophysics Data System (ADS)

Kesamaru, Katsumi; Ohno, Yoshihiro; Sonoda, Daisuke

The paper describes a new approach to simulate the small wind power generating systems using PMSG, in which the output is connected to constant resistive load, such as heaters, through the rectifier and the dc chopper. The dynamics of the wind power generating system is presented, and it is shown by simulation results that this approach is useful for system dynamics, such as starting phenomena.

Modification of Rat Lung Decellularization Protocol Based on Dynamic Conductometry of Working Solution.

PubMed

Kuevda, E V; Gubareva, E A; Gumenyuk, I S; Sotnichenko, A S; Gilevich, I V; Nakokhov, R Z; Rusinova, T V; Yudina, T G; Red'ko, A N; Alekseenko, S N

2017-03-01

We modified the protocol of obtaining of biological scaffolds of rat lungs based on dynamic recording of specific resistivity of working detergent solution (conductometry) during perfusion decellularization. Termination of sodium deoxycholate exposure after attaining ionic equilibrium plateau did not impair the quality of decellularization and preserved structural matrix components, which was confirmed by morphological analysis and quantitative assay of residual DNA.

The escalatory Red Queen: Population extinction and replacement following arms race dynamics in poplar rust.

PubMed

Persoons, Antoine; Hayden, Katherine J; Fabre, Bénédicte; Frey, Pascal; De Mita, Stéphane; Tellier, Aurélien; Halkett, Fabien

2017-04-01

Host-parasite systems provide convincing examples of Red Queen co-evolutionary dynamics. Yet, a key process underscored in Van Valen's theory - that arms race dynamics can result in extinction - has never been documented. One reason for this may be that most sampling designs lack the breadth needed to illuminate the rapid pace of adaptation by pathogen populations. In this study, we used a 25-year temporal sampling to decipher the demographic history of a plant pathogen: the poplar rust fungus, Melampsora larici-populina. A major adaptive event occurred in 1994 with the breakdown of R7 resistance carried by several poplar cultivars widely planted in Western Europe since 1982. The corresponding virulence rapidly spread in M. larici-populina populations and nearly reached fixation in northern France, even on susceptible hosts. Using both temporal records of virulence profiles and temporal population genetic data, our analyses revealed that (i) R7 resistance breakdown resulted in the emergence of a unique and homogeneous genetic group, the so-called cultivated population, which predominated in northern France for about 20 years, (ii) selection for Vir7 individuals brought with it multiple other virulence types via hitchhiking, resulting in an overall increase in the population-wide number of virulence types and (iii) - above all - the emergence of the cultivated population superseded the initial population which predominated at the same place before R7 resistance breakdown. Our temporal analysis illustrates how antagonistic co-evolution can lead to population extinction and replacement, hence providing direct evidence for the escalation process which is at the core of Red Queen dynamics. © 2016 John Wiley & Sons Ltd.

Modeling the infection dynamics of bacteriophages in enteric Escherichia coli: estimating the contribution of transduction to antimicrobial gene spread.

PubMed

Volkova, Victoriya V; Lu, Zhao; Besser, Thomas; Gröhn, Yrjö T

2014-07-01

Animal-associated bacterial communities are infected by bacteriophages, although the dynamics of these infections are poorly understood. Transduction by bacteriophages may contribute to transfer of antimicrobial resistance genes, but the relative importance of transduction among other gene transfer mechanisms is unknown. We therefore developed a candidate deterministic mathematical model of the infection dynamics of enteric coliphages in commensal Escherichia coli in the large intestine of cattle. We assumed the phages were associated with the intestine and were predominantly temperate. Model simulations demonstrated how, given the bacterial ecology and infection dynamics, most (>90%) commensal enteric E. coli bacteria may become lysogens of enteric coliphages during intestinal transit. Using the model and the most liberal assumptions about transduction efficiency and resistance gene frequency, we approximated the upper numerical limits ("worst-case scenario") of gene transfer through specialized and generalized transduction in E. coli by enteric coliphages when the transduced genetic segment is picked at random. The estimates were consistent with a relatively small contribution of transduction to lateral gene spread; for example, generalized transduction delivered the chromosomal resistance gene to up to 8 E. coli bacteria/hour within the population of 1.47 × 10(8) E. coli bacteria/liter luminal contents. In comparison, the plasmidic blaCMY-2 gene carried by ~2% of enteric E. coli was transferred by conjugation at a rate at least 1.4 × 10(3) times greater than our generalized transduction estimate. The estimated numbers of transductants varied nonlinearly depending on the ecology of bacteria available for phages to infect, that is, on the assumed rates of turnover and replication of enteric E. coli. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Modeling the Infection Dynamics of Bacteriophages in Enteric Escherichia coli: Estimating the Contribution of Transduction to Antimicrobial Gene Spread

PubMed Central

Lu, Zhao; Besser, Thomas; Gröhn, Yrjö T.

2014-01-01

Animal-associated bacterial communities are infected by bacteriophages, although the dynamics of these infections are poorly understood. Transduction by bacteriophages may contribute to transfer of antimicrobial resistance genes, but the relative importance of transduction among other gene transfer mechanisms is unknown. We therefore developed a candidate deterministic mathematical model of the infection dynamics of enteric coliphages in commensal Escherichia coli in the large intestine of cattle. We assumed the phages were associated with the intestine and were predominantly temperate. Model simulations demonstrated how, given the bacterial ecology and infection dynamics, most (>90%) commensal enteric E. coli bacteria may become lysogens of enteric coliphages during intestinal transit. Using the model and the most liberal assumptions about transduction efficiency and resistance gene frequency, we approximated the upper numerical limits (“worst-case scenario”) of gene transfer through specialized and generalized transduction in E. coli by enteric coliphages when the transduced genetic segment is picked at random. The estimates were consistent with a relatively small contribution of transduction to lateral gene spread; for example, generalized transduction delivered the chromosomal resistance gene to up to 8 E. coli bacteria/hour within the population of 1.47 × 108 E. coli bacteria/liter luminal contents. In comparison, the plasmidic blaCMY-2 gene carried by ∼2% of enteric E. coli was transferred by conjugation at a rate at least 1.4 × 103 times greater than our generalized transduction estimate. The estimated numbers of transductants varied nonlinearly depending on the ecology of bacteria available for phages to infect, that is, on the assumed rates of turnover and replication of enteric E. coli. PMID:24814786

What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae?

PubMed Central

Colijn, Caroline; Cohen, Ted; Fraser, Christophe; Hanage, William; Goldstein, Edward; Givon-Lavi, Noga; Dagan, Ron; Lipsitch, Marc

2010-01-01

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance. PMID:19940002

Bacterial communities adapted to higher external resistance can reduce the onset potential of anode in microbial fuel cells.

PubMed

Suzuki, Kei; Kato, Yutaka; Yui, Arashi; Yamamoto, Shuji; Ando, Syota; Rubaba, Owen; Tashiro, Yosuke; Futamata, Hiroyuki

2018-05-01

We investigated how bacterial communities adapted to external resistances and exhibited the performance of electricity production in microbial fuel cells (MFCs) with external resistance of 10 Ω (LR-MFC) and 1000 Ω (HR-MFC). The HR-MFC exhibited better performance than the LR-MFC. The power densities of the LR-MFC and the HR-MFC were 5.2 ± 1.6 mW m -2 and 28 ± 9.6 mW m -2 after day 197, respectively. Low-scan cyclic voltammetry analyses indicated that the onset potential of the HR-MFC was more negative than that of the LR-MFC, suggesting that the higher external resistance led to enrichment of the highly current producing bacteria on the anode surface. All clones of Geobacter retrieved from the LR-MFC and the HR-MFC were members of the Geobacter metallireducens clade. Although the population density of Geobacter decreased from days 366-427 in the HR-MFC, the current density was almost maintained. Multidimensional scaling analyses based on denaturing gradient gel electrophoresis profiles indicated that the dynamics of the biofilm and anolytic communities changed synchronously in the two MFCs, but the dynamics of the bacterial communities in the LR-MFC and the HR-MFC were different from each other, reflecting different processes in adaptation to the different external resistances. The results suggest that the microbial community structure was formed by adapting to higher external resistance, exhibiting more negative onset potential and higher performance of the HR-MFC through collaborating with anode-respiring bacteria and fermenters. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Molecular Dynamics Simulation of the Complex PBP-2x with Drug Cefuroxime to Explore the Drug Resistance Mechanism of Streptococcus suis R61

PubMed Central

Xia, Yingjie; Yang, Ming; Xiao, Jingfa; Yu, Jun

2012-01-01

Drug resistance of Streptococcus suis strains is a worldwide problem for both humans and pigs. Previous studies have noted that penicillin-binding protein (PBPs) mutation is one important cause of β-lactam antibiotic resistance. In this study, we used the molecular dynamics (MD) method to study the interaction differences between cefuroxime (CES) and PBP2x within two newly sequenced Streptococcus suis: drug-sensitive strain A7, and drug-resistant strain R61. The MM-PBSA results proved that the drug bound much more tightly to PBP2x in A7 (PBP2x-A7) than to PBP2x in R61 (PBP2x-R61). This is consistent with the evidently different resistances of the two strains to cefuroxime. Hydrogen bond analysis indicated that PBP2x-A7 preferred to bind to cefuroxime rather than to PBP2x-R61. Three stable hydrogen bonds were formed by the drug and PBP2x-A7, while only one unstable bond existed between the drug and PBP2x-R61. Further, we found that the Gln569, Tyr594, and Gly596 residues were the key mutant residues contributing directly to the different binding by pair wise energy decomposition comparison. By investigating the binding mode of the drug, we found that mutant residues Ala320, Gln553, and Thr595 indirectly affected the final phenomenon by topological conformation alteration. Above all, our results revealed some details about the specific interaction between the two PBP2x proteins and the drug cefuroxime. To some degree, this explained the drug resistance mechanism of Streptococcus suis and as a result could be helpful for further drug design or improvement. PMID:22563422

Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.

PubMed

Ge, Yan; Wu, Jiayan; Xia, Yingjie; Yang, Ming; Xiao, Jingfa; Yu, Jun

2012-01-01

Drug resistance of Streptococcus suis strains is a worldwide problem for both humans and pigs. Previous studies have noted that penicillin-binding protein (PBPs) mutation is one important cause of β-lactam antibiotic resistance. In this study, we used the molecular dynamics (MD) method to study the interaction differences between cefuroxime (CES) and PBP2x within two newly sequenced Streptococcus suis: drug-sensitive strain A7, and drug-resistant strain R61. The MM-PBSA results proved that the drug bound much more tightly to PBP2x in A7 (PBP2x-A7) than to PBP2x in R61 (PBP2x-R61). This is consistent with the evidently different resistances of the two strains to cefuroxime. Hydrogen bond analysis indicated that PBP2x-A7 preferred to bind to cefuroxime rather than to PBP2x-R61. Three stable hydrogen bonds were formed by the drug and PBP2x-A7, while only one unstable bond existed between the drug and PBP2x-R61. Further, we found that the Gln569, Tyr594, and Gly596 residues were the key mutant residues contributing directly to the different binding by pair wise energy decomposition comparison. By investigating the binding mode of the drug, we found that mutant residues Ala320, Gln553, and Thr595 indirectly affected the final phenomenon by topological conformation alteration. Above all, our results revealed some details about the specific interaction between the two PBP2x proteins and the drug cefuroxime. To some degree, this explained the drug resistance mechanism of Streptococcus suis and as a result could be helpful for further drug design or improvement.

Enrichment allows identification of diverse, rare elements in metagenomic resistome-virulome sequencing.

PubMed

Noyes, Noelle R; Weinroth, Maggie E; Parker, Jennifer K; Dean, Chris J; Lakin, Steven M; Raymond, Robert A; Rovira, Pablo; Doster, Enrique; Abdo, Zaid; Martin, Jennifer N; Jones, Kenneth L; Ruiz, Jaime; Boucher, Christina A; Belk, Keith E; Morley, Paul S

2017-10-17

Shotgun metagenomic sequencing is increasingly utilized as a tool to evaluate ecological-level dynamics of antimicrobial resistance and virulence, in conjunction with microbiome analysis. Interest in use of this method for environmental surveillance of antimicrobial resistance and pathogenic microorganisms is also increasing. In published metagenomic datasets, the total of all resistance- and virulence-related sequences accounts for < 1% of all sequenced DNA, leading to limitations in detection of low-abundance resistome-virulome elements. This study describes the extent and composition of the low-abundance portion of the resistome-virulome, using a bait-capture and enrichment system that incorporates unique molecular indices to count DNA molecules and correct for enrichment bias. The use of the bait-capture and enrichment system significantly increased on-target sequencing of the resistome-virulome, enabling detection of an additional 1441 gene accessions and revealing a low-abundance portion of the resistome-virulome that was more diverse and compositionally different than that detected by more traditional metagenomic assays. The low-abundance portion of the resistome-virulome also contained resistance genes with public health importance, such as extended-spectrum betalactamases, that were not detected using traditional shotgun metagenomic sequencing. In addition, the use of the bait-capture and enrichment system enabled identification of rare resistance gene haplotypes that were used to discriminate between sample origins. These results demonstrate that the rare resistome-virulome contains valuable and unique information that can be utilized for both surveillance and population genetic investigations of resistance. Access to the rare resistome-virulome using the bait-capture and enrichment system validated in this study can greatly advance our understanding of microbiome-resistome dynamics.

HIV pretreatment drug resistance trends in three geographic areas of Mexico.

PubMed

García-Morales, Claudia; Tapia-Trejo, Daniela; Quiroz-Morales, Verónica S; Navarro-Álvarez, Samuel; Barrera-Arellano, Carlos A; Casillas-Rodríguez, Jesús; Romero-Mora, Karla A; Gómez-Palacio-Schjetnan, María; Murakami-Ogasawara, Akio; Ávila-Ríos, Santiago; Reyes-Terán, Gustavo

2017-11-01

Pretreatment drug resistance (PDR) levels to NNRTI approaching 10% have recently been reported in Mexico. However, subnational differences may exist in PDR prevalence and transmission dynamics. We longitudinally assessed HIV PDR in three geographic areas of Mexico. HIV-infected, antiretroviral-naive individuals were recruited from 2008 to 2016, from the Central Metropolitan Zone (CMZ), Cancun and Tijuana (1194, 773 and 668 respectively). PDR was estimated using the Stanford HIVdb tool from plasma HIV pol sequences. A higher proportion of females, lower education and lower employment rate were observed in Tijuana, while a higher proportion of MSM was observed in the CMZ (P < 0.0001, all cases). For 2012-16, PDR was 13.4%, 8.9% and 11.2% in the CMZ, Tijuana and Cancun respectively. NNRTI PDR was highest in the three regions (8.7%, 4.8% and 8.1% respectively, P < 0.05); nevertheless, NNRTI PDR in Tijuana was lower than in the CMZ (P = 0.01). For 2008-16, we observed increasing efavirenz resistance trends in all regions (P < 0.05, all cases), reaching 11.8%, 6.1% and 8.3% respectively in 2016. Increasing efavirenz resistance was mostly associated with increasing K103N frequency (P = 0.007 CMZ, P = 0.03 Tijuana, not significant for Cancun). Our study suggests different NNRTI PDR prevalence and transmission dynamics in three geographical areas of Mexico. Even when increasing trends in efavirenz resistance were observed in the three areas, our observations support that, in a large country such as Mexico, subnational surveillance and locally tailored interventions to address drug resistance may be a reasonable option. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Plate falling in a fluid: Regular and chaotic dynamics of finite-dimensional models

NASA Astrophysics Data System (ADS)

Kuznetsov, Sergey P.

2015-05-01

Results are reviewed concerning the planar problem of a plate falling in a resisting medium studied with models based on ordinary differential equations for a small number of dynamical variables. A unified model is introduced to conduct a comparative analysis of the dynamical behaviors of models of Kozlov, Tanabe-Kaneko, Belmonte-Eisenberg-Moses and Andersen-Pesavento-Wang using common dimensionless variables and parameters. It is shown that the overall structure of the parameter spaces for the different models manifests certain similarities caused by the same inherent symmetry and by the universal nature of the phenomena involved in nonlinear dynamics (fixed points, limit cycles, attractors, and bifurcations).

The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa

PubMed Central

Toll-Riera, Macarena; Heilbron, Karl

2016-01-01

Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings. PMID:26763710

Study of steel crack resistance under dynamic loading and temperature range 20-300 °C

NASA Astrophysics Data System (ADS)

Novikov, S. A.; Pushkov, V. A.

1996-05-01

The paper describes an experimental technique to measure crack resistance (plane stress-intensity factor) K1C of structural materials at loading rates up to 2ṡ106MPaṡm1/2ṡs-1 and temperatures 20-300 °C. This technique is based on the known Kolsky method using split Hopkinson bars. The tests were performed using compact WOL-specimens of steel St.3.

Electrical pulse generator

DOEpatents

Norris, Neil J.

1979-01-01

A technique for generating high-voltage, wide dynamic range, shaped electrical pulses in the nanosecond range. Two transmission lines are coupled together by resistive elements distributed along the length of the lines. The conductance of each coupling resistive element as a function of its position along the line is selected to produce the desired pulse shape in the output line when an easily produced pulse, such as a step function pulse, is applied to the input line.

Bias voltage dependence of the electron spin depolarization in quantum wires in the quantum Hall regime detected by the resistively detected NMR

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

Chida, K.; Yamauchi, Y.; Arakawa, T.

2013-12-04

We performed the resistively-detected nuclear magnetic resonance (RDNMR) to study the electron spin polarization in the non-equilibrium quantum Hall regime. By measuring the Knight shift, we derive source-drain bias voltage dependence of the electron spin polarization in quantum wires. The electron spin polarization shows minimum value around the threshold voltage of the dynamic nuclear polarization.

Special issue dedicated to the 70th birthday of Glenn F. Webb. Preface.

PubMed

Hinow, Peter; Magal, Pierre; Ruan, Shigui

2015-08-01

This special issue is dedicated to the 70th birthday of Glenn F. Webb. The topics of the 12 articles appearing in this special issue include evolutionary dynamics of population growth, spatio-temporal dynamics in reaction-diffusion biological models, transmission dynamics of infectious diseases, modeling of antibiotic-resistant bacteria in hospitals, analysis of Prion models, age-structured models in ecology and epidemiology, modeling of immune response to infections, modeling of cancer growth, etc. These topics partially represent the broad areas of Glenn's research interest.

Relations between structural and dynamic thermal characteristics of building walls

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

Kossecka, E.; Kosny, J.

1996-10-01

The effect of internal thermal structure on dynamic characteristics of walls is analyzed. The concept of structure factors is introduced and the conditions they impose on response factors are given. Simple examples of multilayer walls, representing different types of thermal resistance and capacity distribution, are analyzed to illustrate general relations between structure factors and response factors. The idea of the ``thermally equivalent wall``, a plane multilayer structure, with dynamic characteristics similar to those of a complex structure, in which three-dimensional heat flow occurs, is presented.

First principles investigation of the unipolar resistive switching mechanism in an interfacial phase change memory based on a GeTe/Sb2Te3 superlattice

NASA Astrophysics Data System (ADS)

Shirakawa, Hiroki; Araidai, Masaaki; Shiraishi, Kenji

2018-04-01

The interfacial phase change memory (iPCM) based on a GeTe/Sb2Te3 superlattice is one of the candidates for future storage class memories. However, the atomic structures of the high and low resistance states (HRS/LRS) remain unclear and the resistive switching mechanism is still under debate. Clarifying the switching mechanism is essential for developing further high-reliability and low-power-consumption iPCM. We propose, on the basis of the results of first-principles molecular dynamics simulations, a mechanism for resistive switching, and describe the atomic structures of the high and low resistance states of iPCM for unipolar switching. Our simulations indicated that switching from HRS to LRS occurs with Joule heating only, while that from LRS to HRS occurs with both hole injection and Joule heating.

Origin of high Coulombic loss during sodiation in Na-Sn battery

NASA Astrophysics Data System (ADS)

Byeon, Young-Woon; Choi, Yong-Seok; Ahn, Jae-Pyoung; Lee, Jae-Chul

2017-03-01

Electrochemical sodiation is performed in crystalline Sn foil using in situ scanning electron microscopy (SEM) to simultaneously measure the changes in the electrical resistivity and volume of the Sn anode in a Na-Sn battery. We observe that sodiation causes an increase in the Sn anode resistivity by six orders of magnitude. Ab initio molecular dynamics simulations of the Na-Sn alloy system demonstrate that the increased resistivity of the anode is caused by the formation of an electrically resistive amorphous NaSn phase (a-NaSn) with a pseudogap. It is also observed that the formation of a-NaSn is always accompanied by a large volume expansion of ∼200%, causing the development of residual tensile stress. The residual stress in turn alters the electronic structure of the a-NaSn phase, further increasing the resistivity of a-NaSn and thus decreasing the energy efficiency of the Na-Sn battery.

Exogenous Salicylic Acid Enhances the Resistance of Wheat Seedlings to Hessian Fly (Diptera: Cecidomyiidae) Infestation Under Heat Stress.

PubMed

Underwood, Joshua; Moch, John; Chen, Ming-Shun; Zhu, Lieceng

2014-10-01

Heat stress exerts significant impact on plant-parasite interactions. Phytohormones, such as salicylic acid (SA), play important roles in plant defense against parasite attacks. Here, we studied the impact of a combination of heat stress and exogenous SA on the resistance of wheat (Triticum aestivum L.) plants to the Hessian fly [Mayetiola destructor (Say)]. We found that the wheat cultivar 'Molly', which contains the resistance gene H13, lost resistance to Hessian fly under heat stress (40°C for 3 and 6 h), and that exogenous application of SA on Molly seedlings right before heat stress can partially prevent the loss of resistance of Molly plants under heat conditions. Our findings have significant implications for understanding the dynamics of plant-insect interactions in the context of heat stress. © 2014 Entomological Society of America.

Treatment resistance in urothelial carcinoma: an evolutionary perspective.

PubMed

Vlachostergios, Panagiotis J; Faltas, Bishoy M

2018-05-02

The emergence of treatment-resistant clones is a critical barrier to cure in patients with urothelial carcinoma. Setting the stage for the evolution of resistance, urothelial carcinoma is characterized by extensive mutational heterogeneity, which is detectable even in patients with early stage disease. Chemotherapy and immunotherapy both act as selective pressures that shape the evolutionary trajectory of urothelial carcinoma throughout the course of the disease. A detailed understanding of the dynamics of evolutionary drivers is required for the rational development of curative therapies. Herein, we describe the molecular basis of the clonal evolution of urothelial carcinomas and the use of genomic approaches to predict treatment responses. We discuss various mechanisms of resistance to chemotherapy with a focus on the mutagenic effects of the DNA dC->dU-editing enzymes APOBEC3 family of proteins. We also review the evolutionary mechanisms underlying resistance to immunotherapy, such as the loss of clonal tumour neoantigens. By dissecting treatment resistance through an evolutionary lens, the field will advance towards true precision medicine for urothelial carcinoma.

Rational design and adaptive management of combination therapies for Hepatitis C virus infection

DOE PAGES

Ke, Ruian; Loverdo, Claude; Qi, Hangfei; ...

2015-06-30

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensatemore » when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.« less

Effect of irradiation-induced plastic flow localization on ductile crack resistance behavior of a 9%Cr tempered martensitic steel

NASA Astrophysics Data System (ADS)

Chaouadi, R.

2008-01-01

This paper examines the effect of irradiation-induced plastic flow localization on the crack resistance behavior. Tensile and crack resistance measurements were performed on Eurofer-97 that was irradiated at 300 °C to neutron doses ranging between 0.3 and 2.1 dpa. A severe degradation of crack resistance behavior is experimentally established at quasi-static loading, in contradiction with the Charpy impact data and the dynamic crack resistance measurements. This degradation is attributed to the dislocation channel deformation phenomenon. At quasi-static loading rate, scanning electron microscopy observations of the fracture surfaces revealed a significant change of fracture topography, mainly from equiaxed dimples (mode I) to shear dimples (mode I + II). With increasing loading rate, the high peak stresses that develop inside the process zone activate much more dislocation sources resulting in a higher density of cross cutting dislocation channels and therefore an almost unaffected crack resistance. These explanations provide a rational to all experimental observations.

Origin of negative resistivity slope in U-based ferromagnets

NASA Astrophysics Data System (ADS)

Havela, L.; Paukov, M.; Buturlim, V.; Tkach, I.; Mašková, S.; Dopita, M.

2018-05-01

Ultra-nanocrystalline UH3-based ferromagnets with TC ≈ 200 K exhibit a flat temperature dependence of electrical resistivity with a negative slope both in the ferromagnetic and paramagnetic range. The ordered state with randomness on atomic scale, equivalent to a non-collinear ferromagnetism, can be affected by magnetic field, supressing the static magnetic disorder, which reduces the resistivity and removes the negative slope. It is deduced that the dynamic magnetic disorder in the paramagnetic state can be conceived as continuation of the static disorder in the ordered state. The experiments, performed for (UH3)0.78Mo0.12Ti0.10, demonstrate that the negative resistivity slope, observed for numerous U-based intermetallics in the paramagnetic state, can be due to the strong disorder effect on resistivity. The resulting weak localization, as a quantum interference effect which increases resistivity, is gradually suppressed by enhanced temperature, contributing by electron-phonon scattering, inelastic in nature and removing the quantum coherence.

Molecular principles behind pyrazinamide resistance due to mutations in panD gene in Mycobacterium tuberculosis.

PubMed

Pandey, Bharati; Grover, Sonam; Tyagi, Chetna; Goyal, Sukriti; Jamal, Salma; Singh, Aditi; Kaur, Jagdeep; Grover, Abhinav

2016-04-25

The latest resurrection of drug resistance poses serious threat to the treatment and control of the disease. Mutations have been detected in panD gene in the Mycobacterium tuberculosis (Mtb) strains. Mutation of histidine to arginine at residue 21 (H21R) and isoleucine to valine at residue 29 (I49V) in the non-active site of panD gene has led to PZA resistance. This study will help in reconnoitering the mechanism of pyrazinamide (PZA) resistance caused due to double mutation identified in the panD gene of M. tuberculosis clinical isolates. It is known that panD gene encodes aspartate decarboxylase essential for β-alanine synthesis that makes it a potential therapeutic drug target for tuberculosis treatment. The knowledge about the molecular mechanism conferring drug resistance in M. tuberculosis is scarce, which is a significant challenge in designing successful therapeutic drug. In this study, structural and dynamic repercussions of H21R-I49V double mutation in panD complexed with PZA have been corroborated through docking and molecular dynamics based simulation. The double mutant (DM) shows low docking score and thus, low binding affinity for PZA as compared to the native protein. It was observed that the mutant protein exhibits more structural fluctuation at the ligand binding site in comparison to the native type. Furthermore, the flexibility and compactness analyses indicate that the double mutation influence interaction of PZA with the protein. The hydrogen-bond interaction patterns further supported our results. The covariance and PCA analysis elucidated that the double mutation affects the collective motion of residues in phase space. The results have been presented with an explanation for the induced drug resistance conferred by the H21R-I49V double mutation in panD gene and gain valuable insight to facilitate the advent of efficient therapeutics for combating resistance against PZA. Copyright © 2016 Elsevier B.V. All rights reserved.

Physical and computational fluid dynamics models for the hemodynamics of the artiodactyl carotid rete.

PubMed

O'Brien, Haley D; Bourke, Jason

2015-12-07

In the mammalian order Artiodactyla, the majority of arterial blood entering the intracranial cavity is supplied by a large arterial meshwork called the carotid rete. This vascular structure functionally replaces the internal carotid artery. Extensive experimentation has demonstrated that the artiodactyl carotid rete drives one of the most effective selective brain cooling mechanisms among terrestrial vertebrates. Less well understood is the impact that the unique morphology of the carotid rete may have on the hemodynamics of blood flow to the cerebrum. It has been hypothesized that, relative to the tubular internal carotid arteries of most other vertebrates, the highly convoluted morphology of the carotid rete may increase resistance to flow during extreme changes in cerebral blood pressure, essentially protecting the brain by acting as a resistor. We test this hypothesis by employing simple and complex physical models to a 3D surface rendering of the carotid rete of the domestic goat, Capra hircus. First, we modeled the potential for increased resistance across the carotid rete using an electrical circuit analog. The extensive branching of the rete equates to a parallel circuit that is bound in series by single tubular arteries, both upstream and downstream. This method calculated a near-zero increase in resistance across the rete. Because basic equations do not incorporate drag, shear-stress, and turbulence, we used computational fluid dynamics to simulate the impact of these computationally intensive factors on resistance. Ultimately, both simple and complex models demonstrated negligible changes in resistance and blood pressure across the arterial meshwork. We further tested the resistive potential of the carotid rete by simulating blood pressures known to occur in giraffes. Based on these models, we found resistance (and blood pressure mitigation as a whole) to be an unlikely function for the artiodactyl carotid rete. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of selective digestive decontamination (SDD) on the gut resistome.

PubMed

Buelow, Elena; Gonzalez, Teresita Bello; Versluis, Dennis; Oostdijk, Evelien A N; Ogilvie, Lesley A; van Mourik, Maaike S M; Oosterink, Els; van Passel, Mark W J; Smidt, Hauke; D'Andrea, Marco Maria; de Been, Mark; Jones, Brian V; Willems, Rob J L; Bonten, Marc J M; van Schaik, Willem

2014-08-01

Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibiotic-resistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches. We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD. The patient microbiota was highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2″)-Ib and an aadE-like gene. We show that aph(2″)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ∼10(4) fold increase to a ∼10(-10) fold decrease in relative abundance during SDD. ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Insights into susceptibility of antiviral drugs against the E119G mutant of 2009 influenza A (H1N1) neuraminidase by molecular dynamics simulations and free energy calculations.

PubMed

Pan, Peichen; Li, Lin; Li, Youyong; Li, Dan; Hou, Tingjun

2013-11-01

Neuraminidase inhibitors (NAIs) play vital roles in controlling human influenza epidemics and pandemics. However, the emergence of new human influenza virus mutant strains resistant to existing antiviral drugs has been becoming a major challenge. Therefore, it is critical to uncover the mechanisms of drug resistance and seek alternative treatments to combat drug resistance. In this study, molecular dynamics (MD) simulations and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) were applied to investigate the different sensitivities of oseltamivir (OTV), zanamivir (ZNV), and peramivir (PRV) against the E119G mutant of 2009 A/H1N1 neuraminidase. The predicted binding free energies indicate that the E119G mutation in NA confers resistance to all of the three studied inhibitors. The ordering of the level of drug resistance predicted by the binding free energies for the three inhibitors is ZNV>PRV>OTV, which agrees well with the experimental data. Drug resistance arises primarily from the unfavorable shifts of the polar interactions between NA and the inhibitors. It comes as a surprise that the mutation of Glu119 that can form strong H-bonds with the inhibitors in the wild-type protein does not have direct impact on the binding affinities of both OTV and PRV due to the regulation of the strong unfavorable polar desolvation energies. The indirectly conformational variations of the inhibitors, which caused by the E119G mutation, are responsible for the loss of the binding free energies. However, for ZNV, the E119G mutation has both direct and indirect influences on the drug binding. The structural and quantitative viewpoint obtained from this study provides valuable information for the rational design of novel and effective drugs to combat drug resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of joint kinetics during free weight and flywheel resistance exercise.

PubMed

Chiu, Loren Z F; Salem, George J

2006-08-01

The most common modality for resistance exercise is free weight resistance. Alternative methods of providing external resistance have been investigated, in particular for use in microgravity environments such as space flight. One alternative modality is flywheel inertial resistance, which generates resistance as a function of the mass, distribution of mass, and angular acceleration of the flywheel. The purpose of this investigation was to characterize net joint kinetics of multijoint exercises performed with a flywheel inertial resistance device in comparison to free weights. Eleven trained men and women performed the front squat, lunge, and push press on separate days with free weight or flywheel resistance, while instrumented for biomechanical analysis. Front squats performed with flywheel resistance required greater contribution of the hip and ankle, and less contribution of the knee, compared to free weight. Push presses performed with flywheel resistance had similar impulse requirements at the knee compared to free weight, but greater impulse requirement at the hip and ankle. As used in this investigation, flywheel inertial resistance increases the demand on the hip extensors and ankle plantarflexors and decreases the mechanical demand on the knee extensors for lower extremity exercises such as the front squat and lunge. Exercises involving dynamic lower and upper extremity actions, such as the push press, may benefit from flywheel inertial resistance, due to the increased mechanical demand on the knee extensors.

Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia.

PubMed

Herling, Carmen D; Abedpour, Nima; Weiss, Jonathan; Schmitt, Anna; Jachimowicz, Ron Daniel; Merkel, Olaf; Cartolano, Maria; Oberbeck, Sebastian; Mayer, Petra; Berg, Valeska; Thomalla, Daniel; Kutsch, Nadine; Stiefelhagen, Marius; Cramer, Paula; Wendtner, Clemens-Martin; Persigehl, Thorsten; Saleh, Andreas; Altmüller, Janine; Nürnberg, Peter; Pallasch, Christian; Achter, Viktor; Lang, Ulrich; Eichhorst, Barbara; Castiglione, Roberta; Schäfer, Stephan C; Büttner, Reinhard; Kreuzer, Karl-Anton; Reinhardt, Hans Christian; Hallek, Michael; Frenzel, Lukas P; Peifer, Martin

2018-02-20

Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.

Verification, Validation and Credibility Assessment of a Computational Model of the Advanced Resistive Exercise Device (ARED)

NASA Technical Reports Server (NTRS)

Werner, C. R.; Humphreys, B. T.; Mulugeta, L.

2014-01-01

The Advanced Resistive Exercise Device (ARED) is the resistive exercise device used by astronauts on the International Space Station (ISS) to mitigate bone loss and muscle atrophy due to extended exposure to microgravity (micro g). The Digital Astronaut Project (DAP) has developed a multi-body dynamics model of biomechanics models for use in spaceflight exercise physiology research and operations. In an effort to advance model maturity and credibility of the ARED model, the DAP performed verification, validation and credibility (VV and C) assessment of the analyses of the model in accordance to NASA-STD-7009 'Standards for Models and Simulations'.

Using resistive readout to probe ultrafast dynamics of a plasmonic sensor

NASA Astrophysics Data System (ADS)

Cheney, Alec; Chen, Borui; Cartwright, Alexander; Thomay, Tim

2018-02-01

Surface plasmons in a DC current lead to an increase in scattering processes, resulting in a measurable increase in electrical resistance of a plasmonic nano-grating. This enables a purely electronic readout of plasmonically mediated optical absorption. We show that there is a time-dependence in these resistance changes on the order of 100ps that we attribute to electron-phonon and phonon-phonon scattering processes in the metal of the nano-gratings. Since plasmonic responses are strongly structurally dependent, an appropriately designed plasmoelectronic detector could potentially offer an extremely fast response at communication wavelengths in a fully CMOS compatible system.

Recent evolution of antibiotic resistance in the anaerobes as compared to previous decades.

PubMed

Boyanova, Lyudmila; Kolarov, Rossen; Mitov, Ivan

2015-02-01

Evolution of antibiotic resistance in the anaerobes was reviewed using recent data covering 2000-2013 as compared to previous years. All studies reported growing moxifloxacin resistance in Bacteroides/Parabacteroides spp. in Europe and USA and in Clostridium difficile in Europe. In half or more studies, the resistance rates in Bacteroides/Parabacteroides spp. to amoxicillin-clavulanate or ampicillin-sulbactam and clindamycin rose. In some studies, an increase in resistance was found in Bacteroides/Parabacteroides spp. to cefoxitin/cefotetan and carbapenems, in Prevotella spp. to penicillins, in anaerobic cocci to clindamycin and in Bacteroides/Parabacteroides spp. and C. difficile to metronidazole. Decreasing resistance was also observed, e.g. in Bacteroides/Parabacteroides spp. to cephalosporins, in Prevotella spp. and C. difficile to tetracyclines and in C. difficile to rifampin. No resistance changes were found to tigecycline, in Bacteroides/Parabacteroides spp. to chloramphenicol and in C. difficile to vancomycin. Factors influencing the resistance were the species, ribotype, country, hospital centre, antibiotic consumption and specimen type. In conclusion, the antibiotic resistance changes in the anaerobes are diverse and dynamic. Regular national surveys of resistance and both anaerobic microbiology and susceptibility testing of the isolates become more and more valuable. Copyright © 2014 Elsevier Ltd. All rights reserved.

On the early and developed stages of surface condensation: competition mechanism between interfacial and condensate bulk thermal resistances.

PubMed

Sun, Jie; Wang, Hua Sheng

2016-10-10

We use molecular dynamics simulation to investigate the early and developed stages of surface condensation. We find that the liquid-vapor and solid-liquid interfacial thermal resistances depend on the properties of solid and fluid, which are time-independent, while the condensate bulk thermal resistance depends on the condensate thickness, which is time-dependent. There exists intrinsic competition between the interfacial and condensate bulk thermal resistances in timeline and the resultant total thermal resistance determines the condensation intensity for a given vapor-solid temperature difference. We reveal the competition mechanism that the interfacial thermal resistance dominates at the onset of condensation and holds afterwards while the condensate bulk thermal resistance gradually takes over with condensate thickness growing. The weaker the solid-liquid bonding, the later the takeover occurs. This competition mechanism suggests that only when the condensate bulk thermal resistance is reduced after it takes over the domination can the condensation be effectively intensified. We propose a unified theoretical model for the thermal resistance analysis by making dropwise condensation equivalent to filmwise condensation. We further find that near a critical point (contact angle being ca. 153°) the bulk thermal resistance has the least opportunity to take over the domination while away from it the probability increases.

On the early and developed stages of surface condensation: competition mechanism between interfacial and condensate bulk thermal resistances

PubMed Central

Sun, Jie; Wang, Hua Sheng

2016-01-01

We use molecular dynamics simulation to investigate the early and developed stages of surface condensation. We find that the liquid-vapor and solid-liquid interfacial thermal resistances depend on the properties of solid and fluid, which are time-independent, while the condensate bulk thermal resistance depends on the condensate thickness, which is time-dependent. There exists intrinsic competition between the interfacial and condensate bulk thermal resistances in timeline and the resultant total thermal resistance determines the condensation intensity for a given vapor-solid temperature difference. We reveal the competition mechanism that the interfacial thermal resistance dominates at the onset of condensation and holds afterwards while the condensate bulk thermal resistance gradually takes over with condensate thickness growing. The weaker the solid-liquid bonding, the later the takeover occurs. This competition mechanism suggests that only when the condensate bulk thermal resistance is reduced after it takes over the domination can the condensation be effectively intensified. We propose a unified theoretical model for the thermal resistance analysis by making dropwise condensation equivalent to filmwise condensation. We further find that near a critical point (contact angle being ca. 153°) the bulk thermal resistance has the least opportunity to take over the domination while away from it the probability increases. PMID:27721397

Mechanical properties of the gastro-esophageal junction in health, achalasia, and scleroderma.

PubMed

Mearin, F; Fonollosa, V; Vilardell, M; Malagelada, J R

2000-07-01

Manometric assessment of the gastro-esophageal junction (GEJ) is deceptive in that ignores key dynamic properties of the junction, such as resistance to flow and compliance. Our aim was to investigate the mechanical properties of the GEJ comprising intraluminal pressure (measured by manometry), resistance to flow and compliance (measured by resistometry). We studied 8 healthy subjects, 11 patients with achalasia and 11 patients with scleroderma. We used a pneumatic resistometer, previously developed and validated in our laboratory. The resistometer consists of a flaccid polyurethane 5-cm cylinder connected to an electronically regulated nitrogen-injection system; the instrument records nitrogen flow through the cylinder while maintaining a constant pressure gradient between its proximal and distal ends. By placing the cylinder successively in the proximal stomach and along the GEJ we measured the GEJ-gastric resistance gradient (GEJ resistance minus gastric resistance) and were able to calculate the cumulative resistance (sum of resistance exerted at each pressure level), peak resistance (at any injection pressure), nil resistance point (injection pressure in mmHg at which GEJ resistance equals gastric resistance), and compliance slope (flow/pressure relationship). We found that GEJ resistance to flow (cumulative resistance, peak resistance, and nil resistance point) is significantly increased in achalasia and decreased in scleroderma (P < 0.05 versus health) while GEJ compliance is diminished in achalasia (P < 0.05 versus health) and normal in scleroderma. Achalasia is a disease characterized by increased GEJ resistance and rigidity. By contrast, although scleroderma is characterized by decreased GEJ resistance, GEJ compliance may be normal.

Flow resistance dynamics in step‐pool channels: 2. Partitioning between grain, spill, and woody debris resistance

USGS Publications Warehouse

Wilcox, Andrew C.; Nelson, Jonathan M.; Wohl, Ellen E.

2006-01-01

In step‐pool stream channels, flow resistance is created primarily by bed sediments, spill over step‐pool bed forms, and large woody debris (LWD). In order to measure resistance partitioning between grains, steps, and LWD in step‐pool channels we completed laboratory flume runs in which total resistance was measured with and without grains and steps, with various LWD configurations, and at multiple slopes and discharges. Tests of additive approaches to resistance partitioning found that partitioning estimates are highly sensitive to the order in which components are calculated and that such approaches inflate the values of difficult‐to‐measure components that are calculated by subtraction from measured components. This effect is especially significant where interactions between roughness features create synergistic increases in resistance such that total resistance measured for combinations of resistance components greatly exceeds the sum of those components measured separately. LWD contributes large proportions of total resistance by creating form drag on individual pieces and by increasing the spill resistance effect of steps. The combined effect of LWD and spill over steps was found to dominate total resistance, whereas grain roughness on step treads was a small component of total resistance. The relative contributions of grain, spill, and woody debris resistance were strongly influenced by discharge and to a lesser extent by LWD density. Grain resistance values based on published formulas and debris resistance values calculated using a cylinder drag approach typically underestimated analogous flume‐derived values, further illustrating sources of error in partitioning methods and the importance of accounting for interaction effects between resistance components.

Flow resistance dynamics in step-pool channels: 2. Partitioning between grain, spill, and woody debris resistance

NASA Astrophysics Data System (ADS)

Wilcox, Andrew C.; Nelson, Jonathan M.; Wohl, Ellen E.

2006-05-01

In step-pool stream channels, flow resistance is created primarily by bed sediments, spill over step-pool bed forms, and large woody debris (LWD). In order to measure resistance partitioning between grains, steps, and LWD in step-pool channels we completed laboratory flume runs in which total resistance was measured with and without grains and steps, with various LWD configurations, and at multiple slopes and discharges. Tests of additive approaches to resistance partitioning found that partitioning estimates are highly sensitive to the order in which components are calculated and that such approaches inflate the values of difficult-to-measure components that are calculated by subtraction from measured components. This effect is especially significant where interactions between roughness features create synergistic increases in resistance such that total resistance measured for combinations of resistance components greatly exceeds the sum of those components measured separately. LWD contributes large proportions of total resistance by creating form drag on individual pieces and by increasing the spill resistance effect of steps. The combined effect of LWD and spill over steps was found to dominate total resistance, whereas grain roughness on step treads was a small component of total resistance. The relative contributions of grain, spill, and woody debris resistance were strongly influenced by discharge and to a lesser extent by LWD density. Grain resistance values based on published formulas and debris resistance values calculated using a cylinder drag approach typically underestimated analogous flume-derived values, further illustrating sources of error in partitioning methods and the importance of accounting for interaction effects between resistance components.

Resistance training for activity limitations in older adults with skeletal muscle function deficits: a systematic review.

PubMed

Papa, Evan V; Dong, Xiaoyang; Hassan, Mahdi

2017-01-01

Human aging results in a variety of changes to skeletal muscle. Sarcopenia is the age-associated loss of muscle mass and is one of the main contributors to musculoskeletal impairments in the elderly. Previous research has demonstrated that resistance training can attenuate skeletal muscle function deficits in older adults, however few articles have focused on the effects of resistance training on functional mobility. The purpose of this systematic review was to 1) present the current state of literature regarding the effects of resistance training on functional mobility outcomes for older adults with skeletal muscle function deficits and 2) provide clinicians with practical guidelines that can be used with seniors during resistance training, or to encourage exercise. We set forth evidence that resistance training can attenuate age-related changes in functional mobility, including improvements in gait speed, static and dynamic balance, and fall risk reduction. Older adults should be encouraged to participate in progressive resistance training activities, and should be admonished to move along a continuum of exercise from immobility, toward the recommended daily amounts of activity.

Is a larger refuge always better? Dispersal and dose in pesticide resistance evolution

PubMed Central

Takahashi, Daisuke; Yamanaka, Takehiko; Sudo, Masaaki; Andow, David A.

2017-01-01

The evolution of resistance against pesticides is an important problem of modern agriculture. The high‐dose/refuge strategy, which divides the landscape into treated and nontreated (refuge) patches, has proven effective at delaying resistance evolution. However, theoretical understanding is still incomplete, especially for combinations of limited dispersal and partially recessive resistance. We reformulate a two‐patch model based on the Comins model and derive a simple quadratic approximation to analyze the effects of limited dispersal, refuge size, and dominance for high efficacy treatments on the rate of evolution. When a small but substantial number of heterozygotes can survive in the treated patch, a larger refuge always reduces the rate of resistance evolution. However, when dominance is small enough, the evolutionary dynamics in the refuge population, which is indirectly driven by migrants from the treated patch, mainly describes the resistance evolution in the landscape. In this case, for small refuges, increasing the refuge size will increase the rate of resistance evolution. Our analysis distils major driving forces from the model, and can provide a framework for understanding directional selection in source‐sink environments. PMID:28422284

Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics

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

Agniswamy, Johnson; Louis, John M.; Roche, Julien

We report structural analysis of HIV protease variant PRS17 which was rationally selected by machine learning to represent wide classes of highly drug-resistant variants. Crystal structures were solved of PRS17 in the inhibitor-free form and in complex with antiviral inhibitor, darunavir. Despite its 17 mutations, PRS17 has only one mutation (V82S) in the inhibitor/substrate binding cavity, yet exhibits high resistance to all clinical inhibitors. PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type PR. Comparable binding affinity of 8000-fold weaker thanmore » PR is seen for drug resistant mutant PR20, which bears 3 mutations associated with major resistance to darunavir (I47V, I54L and I84V). Inhibitor-free PRS17 shows an open flap conformation with a curled tip correlating with G48V flap mutation. NMR studies on inactive PRS17 D25N unambiguously confirm that the flaps adopt mainly an open conformation in solution very similar to that in the inhibitor-free crystal structure. In PRS17, the hinge loop cluster of mutations, E35D, M36I and S37D, contributes to the altered flap dynamics by a mechanism similar to that of PR20. An additional K20R mutation anchors an altered conformation of the hinge loop. Flap mutations M46L and G48V in PRS17/DRV complex alter the Phe53 conformation by steric hindrance between the side chains. Unlike the L10F mutation in PR20, L10I in PRS17 does not break the inter-subunit ion pair or diminish the dimer stability, consistent with a very low dimer dissociation constant comparable to that of wild type PR. Distal mutations A71V, L90M and I93L propagate alterations to the catalytic site of PRS17. PRS17 exhibits a molecular mechanism whereby mutations act synergistically to alter the flap dynamics resulting in significantly weaker binding yet maintaining active site contacts with darunavir.« less

Mobility dynamics of migrant workers and their socio-behavioral parameters related to malaria in Tier II, Artemisinin Resistance Containment Zone, Myanmar.

PubMed

Hlaing, Thaung; Wai, Khin Thet; Oo, Tin; Sint, Nyan; Min, Tun; Myar, Shwe; Lon, Khin Nan; Naing, Myo Myint; Tun, Tet Toe; Maung, Nay Lin Yin; Galappaththy, Gawrie N L; Thimarsan, Krongthong; Wai, Tin Tin; Thaung, Lwin Ni Ni

2015-09-14

Areas with dynamic population movements are likely to be associated with higher levels of drug-resistant malaria. Myanmar Artemisinin Resistance Containment (MARC) Project has been launching since 2012. One of its components includes enhancing strategic approaches for mobile/migrant populations. We aimed to ascertain the estimated population of mobile migrant workers and their families in terms of stability in work setting in townships classified as tier II (areas with significant inflows of people from areas with credible evidence of artemisinin resistance) for Artemisinin resistance; to identify knowledge, attitudes and practices related to prevention and control of malaria and to recommend cost-effective strategies in planning for prevention and control of malaria. A prospective cross-sectional study conducted between June to December 2013 that covered 1,899 migrant groups from 16 tier II townships of Bago Region, and Kayin and Kayah States. Trained data collectors used a pre-tested and subsequently modified questionnaire and interviewed 2,381 respondents. Data of migrant groups were analyzed and compared by category depending upon the stability of their work setting. The estimated population of the 1,899 migrant groups categorized into three on the nature of their work setting was 56,030. Bago region was the commonest reported source of origin of migrant groups as well as their transit. Malaria volunteers were mostly within the reach of category 1 migrant groups (43/66, 65.2 %). Less stable migrant groups in category 3 had limited access to malaria information (14.7 %) and malaria care providers (22.1 %), low level of awareness and use of long-lasting insecticide-treated nets (46.6 and 38.8 %). Also, they had poor knowledge on malaria prevention on confirming suspected malaria and on using artemisinin combined therapy (ACT). Within two weeks prior to the survey, only 16.5 % of respondents in all categories combined reported acute undifferentiated fever. Mobility dynamics of migrant groups was complex and increased their vulnerability to malaria. This phenomenon was accentuated in less stable areas. Even though migrant workers were familiar with rapid diagnostic tests for malaria, ACT still needed wide recognition to improve practices supportive of MARC including the use of appropriate personal protection. High mobility calls for re-designation of tier II townships to optimize ACT resistance containment.

Studies of new perfluoroether elastomeric sealants. [for aircraft fuel tanks

NASA Technical Reports Server (NTRS)

Basiulis, D. I.; Salisbury, D. P.

1981-01-01

Channel and filleting sealants were developed successfully from cyano and diamidoxime terminated perfluoro alkylene ether prepolymers. The prepolymers were polymerized, formulated and tested. The polymers and/or formulations therefrom were evaluated as to their physical, mechanical and chemical properties (i.e., specific gravity, hardness, nonvolatile content, corrosion resistance, stress corrosion, pressure rupture resistance, low temperature flexibility, gap sealing efficiency, tensile strength and elongation, dynamic mechanical behavior, compression set, fuel resistance, thermal properties and processability). Other applications of the formulated polymrs and incorporation of the basic prepolymers into other polymeric systems were investigated. A cyano terminated perfluoro alkylene oxide triazine was formulated and partially evaluated. The channel sealant in its present formulation has excellent pressure rupture resistance and surpasses present MIL specifications before and after fuel and heat aging.

Evaluation of fatigue life of CRM-reinforced SMA and its relationship to dynamic stiffness.

PubMed

Mashaan, Nuha Salim; Karim, Mohamed Rehan; Abdel Aziz, Mahrez; Ibrahim, Mohd Rasdan; Katman, Herda Yati; Koting, Suhana

2014-01-01

Fatigue cracking is an essential problem of asphalt concrete that contributes to pavement damage. Although stone matrix asphalt (SMA) has significantly provided resistance to rutting failure, its resistance to fatigue failure is yet to be fully addressed. The aim of this study is to evaluate the effect of crumb rubber modifier (CRM) on stiffness and fatigue properties of SMA mixtures at optimum binder content, using four different modification levels, namely, 6%, 8%, 10%, and 12% CRM by weight of the bitumen. The testing undertaken on the asphalt mix comprises the dynamic stiffness (indirect tensile test), dynamic creep (repeated load creep), and fatigue test (indirect tensile fatigue test) at temperature of 25°C. The indirect tensile fatigue test was conducted at three different stress levels (200, 300, and 400 kPa). Experimental results indicate that CRM-reinforced SMA mixtures exhibit significantly higher fatigue life compared to the mixtures without CRM. Further, higher correlation coefficient was obtained between the fatigue life and resilient modulus as compared to permanent strain; thus resilient modulus might be a more reliable indicator in evaluating the fatigue life of asphalt mixture.

Dynamic Fluid in a Porous Transducer-Based Angular Accelerometer

PubMed Central

Cheng, Siyuan; Fu, Mengyin; Wang, Meiling; Ming, Li; Fu, Huijin; Wang, Tonglei

2017-01-01

This paper presents a theoretical model of the dynamics of liquid flow in an angular accelerometer comprising a porous transducer in a circular tube of liquid. Wave speed and dynamic permeability of the transducer are considered to describe the relation between angular acceleration and the differential pressure on the transducer. The permeability and streaming potential coupling coefficient of the transducer are determined in the experiments, and special prototypes are utilized to validate the theoretical model in both the frequency and time domains. The model is applied to analyze the influence of structural parameters on the frequency response and the transient response of the fluidic system. It is shown that the radius of the circular tube and the wave speed affect the low frequency gain, as well as the bandwidth of the sensor. The hydrodynamic resistance of the transducer and the cross-section radius of the circular tube can be used to control the transient performance. The proposed model provides the basic techniques to achieve the optimization of the angular accelerometer together with the methodology to control the wave speed and the hydrodynamic resistance of the transducer. PMID:28230793

Dynamic calibration of a wheelchair dynamometer.

PubMed

DiGiovine, C P; Cooper, R A; Boninger, M L

2001-01-01

The inertia and resistance of a wheelchair dynamometer must be determined in order to compare the results of one study to another, independent of the type of device used. The purpose of this study was to describe and implement a dynamic calibration test for characterizing the electro-mechanical properties of a dynamometer. The inertia, the viscous friction, the kinetic friction, the motor back-electromotive force constant, and the motor constant were calculated using three different methods. The methodology based on a dynamic calibration test along with a nonlinear regression analysis produced the best results. The coefficient of determination comparing the dynamometer model output to the measured angular velocity and torque was 0.999 for a ramp input and 0.989 for a sinusoidal input. The inertia and resistance were determined for the rollers and the wheelchair wheels. The calculation of the electro-mechanical parameters allows for the complete description of the propulsive torque produced by an individual, given only the angular velocity and acceleration. The measurement of the electro-mechanical properties of the dynamometer as well as the wheelchair/human system provides the information necessary to simulate real-world conditions.

Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface

DOE PAGES

Lopez, Cesar A.; Travers, Timothy; Pos, Klaas M.; ...

2017-11-28

Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm thatmore » the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.« less

Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface

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

Lopez, Cesar A.; Travers, Timothy; Pos, Klaas M.

Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm thatmore » the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.« less

A Discrete Events Delay Differential System Model for Transmission of Vancomycin-Resistant Enterococcus (VRE) in Hospitals

DTIC Science & Technology

2010-09-19

estimated directly form the surveillance data Infection control measures were implemented in the form of health care worker hand - hygiene before and after...hospital infections , is used to motivate possibilities of modeling nosocomial infec- tion dynamics. This is done in the context of hospital monitoring and...model development. Key Words: Delay equations, discrete events, nosocomial infection dynamics, surveil- lance data, inverse problems, parameter

Bi-metal foil gas dynamic bearings with bimorph piezoelectric foils

NASA Astrophysics Data System (ADS)

Sytin, A.; Rodichev, A.; Kulkov, A.

2017-08-01

The present paper considers application of bi-metal materials and coatings to provide necessary strength and wear resistance of the surfaces of rigid and elastic gas dynamic bearings. Authors suggest using multi-layer foils with bimorph piezoelectric elements that operate in the generator regime to determine the deformation of elastic elements, and in the actuator regime to form an optimal shape of the surface of the bearing.

Physics of cancer propagation: A game theory perspective

NASA Astrophysics Data System (ADS)

Cleveland, Chris; Liao, David; Austin, Robert

2012-03-01

This is a theoretical paper which examines at a game theoretical perspective the dynamics of cooperators and cheater cells under metabolic stress conditions and high spatial heterogeneity. Although the ultimate aim of this work is to understand the dynamics of cancer tumor evolution under stress, we use a simple bacterial model to gain fundamental insights into the progression of resistance to drugs under high competition and stress conditions.

The fabrication of flip-covered plasmonic nanostructure surfaces with enhanced wear resistance

NASA Astrophysics Data System (ADS)

Jung, Joo-Yun; Sung, Sang-Keun; Kim, Kwang-Seop; Cheon, So-Hui; Lee, Jihye; Choi, Jun-Hyuk; Lee, Eungsug

2017-01-01

Exposed nanostructure surfaces often suffer from external dynamic wear, particularly when used in human interaction, resulting in surface defects and the degradation of plasmonic resonance properties particularly in terms of transmittance extinction rate and peak-to-valley slope. In this work, a method for the fabrication of flip-covered silver nanostructure-arrayed surfaces is shown to enhance wear resistance. Selectively transferred silver dot and silver webbed-trench exposed reference samples were fabricated by metal nanoimprint, and flip-covered samples were created by flipping and bonding reference samples onto a PET film coated with an adhesive layer. The samples' spectral transmittance was measured before and after a dynamic wear test. Some spectral shift was observed due to the change in refractive index of the surrounding media, but this was not as significant as the effects of the other chosen geometry factors. It was found that dynamic wear had a greater effect on the plasmonic resonance behavior of the exposed samples than in those that had been flip-covered. This suggests that flip-covering may be an effective strategy for the protection of plasmonic resonators against dynamic wear. It is expected that the slight variations in spectral transmittance could be compensated through proper tuning of the sample geometry.

Vibration properties of and power harvested by a system of electromagnetic vibration energy harvesters that have electrical dynamics

NASA Astrophysics Data System (ADS)

Cooley, Christopher G.

2017-09-01

This study investigates the vibration and dynamic response of a system of coupled electromagnetic vibration energy harvesting devices that each consist of a proof mass, elastic structure, electromagnetic generator, and energy harvesting circuit with inductance, resistance, and capacitance. The governing equations for the coupled electromechanical system are derived using Newtonian mechanics and Kirchhoff circuit laws for an arbitrary number of these subsystems. The equations are cast in matrix operator form to expose the device's vibration properties. The device's complex-valued eigenvalues and eigenvectors are related to physical characteristics of its vibration. Because the electrical circuit has dynamics, these devices have more natural frequencies than typical electromagnetic vibration energy harvesters that have purely resistive circuits. Closed-form expressions for the steady state dynamic response and average power harvested are derived for devices with a single subsystem. Example numerical results for single and double subsystem devices show that the natural frequencies and vibration modes obtained from the eigenvalue problem agree with the resonance locations and response amplitudes obtained independently from forced response calculations. This agreement demonstrates the usefulness of solving eigenvalue problems for these devices. The average power harvested by the device differs substantially at each resonance. Devices with multiple subsystems have multiple modes where large amounts of power are harvested.

Dynamic thermal characteristics of heat pipe via segmented thermal resistance model for electric vehicle battery cooling

NASA Astrophysics Data System (ADS)

Liu, Feifei; Lan, Fengchong; Chen, Jiqing

2016-07-01

Heat pipe cooling for battery thermal management systems (BTMSs) in electric vehicles (EVs) is growing due to its advantages of high cooling efficiency, compact structure and flexible geometry. Considering the transient conduction, phase change and uncertain thermal conditions in a heat pipe, it is challenging to obtain the dynamic thermal characteristics accurately in such complex heat and mass transfer process. In this paper, a ;segmented; thermal resistance model of a heat pipe is proposed based on thermal circuit method. The equivalent conductivities of different segments, viz. the evaporator and condenser of pipe, are used to determine their own thermal parameters and conditions integrated into the thermal model of battery for a complete three-dimensional (3D) computational fluid dynamics (CFD) simulation. The proposed ;segmented; model shows more precise than the ;non-segmented; model by the comparison of simulated and experimental temperature distribution and variation of an ultra-thin micro heat pipe (UMHP) battery pack, and has less calculation error to obtain dynamic thermal behavior for exact thermal design, management and control of heat pipe BTMSs. Using the ;segmented; model, the cooling effect of the UMHP pack with different natural/forced convection and arrangements is predicted, and the results correspond well to the tests.

Investigating the dynamic nature of the ABC transporters: ABCB1 and MsbA as examples for the potential synergies of MD theory and EPR applications.

PubMed

Stockner, Thomas; Mullen, Anna; MacMillan, Fraser

2015-10-01

ABC transporters are primary active transporters found in all kingdoms of life. Human multidrug resistance transporter ABCB1, or P-glycoprotein, has an extremely broad substrate spectrum and confers resistance against chemotherapy drug treatment in cancer cells. The bacterial ABC transporter MsbA is a lipid A flippase and a homolog to the human ABCB1 transporter, with which it partially shares its substrate spectrum. Crystal structures of MsbA and ABCB1 have been solved in multiple conformations, providing a glimpse into the possible conformational changes the transporter could be going through during the transport cycle. Crystal structures are inherently static, while a dynamic picture of the transporter in motion is needed for a complete understanding of transporter function. Molecular dynamics (MD) simulations and electron paramagnetic resonance (EPR) spectroscopy can provide structural information on ABC transporters, but the strength of these two methods lies in the potential to characterise the dynamic regime of these transporters. Information from the two methods is quite complementary. MD simulations provide an all atom dynamic picture of the time evolution of the molecular system, though with a narrow time window. EPR spectroscopy can probe structural, environmental and dynamic properties of the transporter in several time regimes, but only through the attachment sites of an exogenous spin label. In this review the synergistic effects that can be achieved by combining the two methods are highlighted, and a brief methodological background is also presented. © 2015 Authors; published by Portland Press Limited.

Topological Properties and the Dynamical Crossover from Mixed-Valence to Kondo-Lattice Behavior in the Golden Phase of SmS.

PubMed

Kang, Chang-Jong; Choi, Hong Chul; Kim, Kyoo; Min, B I

2015-04-24

We have investigated temperature-dependent behaviors of electronic structure and resistivity in a mixed-valent golden phase of SmS, based on the dynamical mean-field-theory band-structure calculations. Upon cooling, the coherent Sm 4f bands are formed to produce the hybridization-induced pseudogap near the Fermi level, and accordingly the topology of the Fermi surface is changed to exhibit a Lifshitz-like transition. The surface states emerging in the bulk gap region are found to be not topologically protected states but just typical Rashba spin-polarized states, indicating that SmS is not a topological Kondo semimetal. From the analysis of anomalous resistivity behavior in SmS, we have identified universal energy scales, which characterize the Kondo-mixed-valent semimetallic systems.

Dynamics of epidemic spreading model with drug-resistant variation on scale-free networks

NASA Astrophysics Data System (ADS)

Wan, Chen; Li, Tao; Zhang, Wu; Dong, Jing

2018-03-01

Considering the influence of the virus' drug-resistant variation, a novel SIVRS (susceptible-infected-variant-recovered-susceptible) epidemic spreading model with variation characteristic on scale-free networks is proposed in this paper. By using the mean-field theory, the spreading dynamics of the model is analyzed in detail. Then, the basic reproductive number R0 and equilibriums are derived. Studies show that the existence of disease-free equilibrium is determined by the basic reproductive number R0. The relationships between the basic reproductive number R0, the variation characteristic and the topology of the underlying networks are studied in detail. Furthermore, our studies prove the global stability of the disease-free equilibrium, the permanence of epidemic and the global attractivity of endemic equilibrium. Numerical simulations are performed to confirm the analytical results.

Simplifications in modelling of dynamical response of coupled electro-mechanical system

NASA Astrophysics Data System (ADS)

Darula, Radoslav; Sorokin, Sergey

2016-12-01

The choice of a most suitable model of an electro-mechanical system depends on many variables, such as a scale of the system, type and frequency range of its operation, or power requirements. The article focuses on the model of the electromagnetic element used in passive regime (no feedback loops are assumed) and a general lumped parameter model (a conventional mass-spring-damper system coupled to an electric circuit consisting of a resistance, an inductance and a capacitance) is compared with its simplified version, where the full RLC circuit is replaced with its RL simplification, i.e. the capacitance of the electric system is neglected and just its inductance and the resistance are considered. From the comparison of dynamical responses of these systems, the range of applicability of a simplified model is assessed for free as well as forced vibration.

Microscopic dynamics research on the "mature" process of dye-sensitized solar cells after injection of highly concentrated electrolyte.

PubMed

Liang, Zhongguan; Liu, Weiqing; Chen, Jun; Hu, Linhua; Dai, Songyuan

2015-01-21

After injection of electrolyte, the internal three-dimensional solid-liquid penetration system of dye-sensitized solar cells (DSCs) can take a period of time to reach "mature" state. This paper studies the changes of microscopic processes of DSCs including TiO2 energy-level movement, localized state distribution, charge accumulation, electron transport, and recombination dynamics, from the beginning of electrolyte injection to the time of reached mature state. The results show that the microscopic dynamics process of DSCs exhibited a time-dependent behavior and achieved maturity ∼12 h after injecting the electrolyte into DSCs. Within 0-12 h, several results were observed: (1) the conduction band edge of TiO2 moved slightly toward negative potential direction; (2) the localized states in the band gap of TiO2 was reduced according to the same distribution law; (3) the transport resistance in TiO2 film increased, and electron transport time was prolonged as the time of maturity went on, which indicated that the electron transport process is impeded gradually; (4) the recombination resistance at the TiO2/electrolyte (EL) interface increases, and electron lifetime gradually extends, therefore, the recombination process is continuously suppressed. Furthermore, results suggest that the parameters of EL/Pt-transparent conductive oxide (TCO) interface including the interfacial capacitance, electron-transfer resistance, and transfer time constant would change with time of maturity, indicating that the EL/Pt-TCO interface is a potential factor affecting the mature process of DSCs.

Validated linear dynamic model of electrically-shunted magnetostrictive transducers with application to structural vibration control

NASA Astrophysics Data System (ADS)

Scheidler, Justin J.; Asnani, Vivake M.

2017-03-01

This paper presents a linear model of the fully-coupled electromechanical behavior of a generally-shunted magnetostrictive transducer. The impedance and admittance representations of the model are reported. The model is used to derive the effect of the shunt’s electrical impedance on the storage modulus and loss factor of the transducer without neglecting the inherent resistance of the transducer’s coil. The expressions are normalized and then shown to also represent generally-shunted piezoelectric materials that have a finite leakage resistance. The generalized expressions are simplified for three shunts: resistive, series resistive-capacitive, and inductive, which are considered for shunt damping, resonant shunt damping, and stiffness tuning, respectively. For each shunt, the storage modulus and loss factor are plotted for a wide range of the normalized parameters. Then, important trends and their impact on different applications are discussed. An experimental validation of the transducer model is presented for the case of resistive and resonant shunts. The model closely predicts the measured response for a variety of operating conditions. This paper also introduces a model for the dynamic compliance of a vibrating structure that is coupled to a magnetostrictive transducer for shunt damping and resonant shunt damping applications. This compliance is normalized and then shown to be analogous to that of a structure that is coupled to a piezoelectric material. The derived analogies allow for the observations and equations in the existing literature on structural vibration control using shunted piezoelectric materials to be directly applied to the case of shunted magnetostrictive transducers.

Mnemiopsis leidyi Gut Harbors Seasonally Variant and Commensal Microbial Assemblages

NASA Astrophysics Data System (ADS)

Mariita, R. M.; Hossain, M. J.; Liles, M. R.; Moss, A.

2016-02-01

Studies have shown that with widespread use of antibiotics in human and domestic animal populations, antibiotic resistance becomes increasingly common in the environment. Estuaries provide ideal conditions for acquisition and dissemination of drug resistance genes because they serve as sinks for pollution. This study aimed to identify M. leidyi microbial diversity and richness and their potential to act as vectors for antibiotic resistance determinants (ARDs). M. leidyi, although native to study area are highly invasive. Metagenomic analyses indicate that there are temporal variations of bacterioplankton assemblages in M. leidyi gut. Overall, Proteobacteria and Actinobacteria are the most abundant phyla. Despite the temporal dynamics in the microbial assemblages in M. leidyi gut, they seem to retain Propionibacterium acnes (gut microbiota in some insects) and select proteobacteria across all seasons. The results contradict previous studies that suggest that M. leidyi does not have constant a microbiota, but only seasonally variant microbial assemblages. Here we reveal the presence of M. leidyi gut ARDs in winter and summer, probably because of the ctenophores' positive geotaxis during rough surface conditions. Genes responsible for resistance to fluoroquinolones, multidrug resistance efflux pumps, mercuric reductase, copper homeostasis and blaR1 genes were observed. This is the first study to demonstrate that M. leidyi harbors constant microbiota and provides a baseline for understanding M. leidyi gut microbial and ARDs ecology. It also suggests that M. leidyi bacterial taxonomic and functional dynamics is influenced by season. Funding: Alabama EPSCoR GRSP fellowship, AU-CMB fellowship, NSF EPS-1158862, USDA-Hatch 370225-310100 (AGM, ML).

Dynamic Behavior and Optimization of Advanced Armor Ceramics: January-December 2012 Annual Report

DTIC Science & Technology

2015-03-01

tasks are reviewed: Nanostructured Armor Ceramics: Focus on Boron Carbide; The Role of Microstructure in the Impact Resistance for Silicon Carbide...Task 2: The Role of Microstructure in the Impact Resistance for Silicon Carbide (SiC), Core Program 22 3.1 Long-Range Goals 22 3.2 Background 22 3.3...from a 2-gr drop test using corn starch as a C source; D(0.9) = 1.27 μm ....................................................................12 Fig

A Compatibility Assessment and Comparison of the Flame Resistant Chemical-Biological (CB) Overgarment with the Standard ’A’ CB Overgarment.

DTIC Science & Technology

1982-01-01

Overgarment-Dynamics .............. .19 TABLES 1. Basic Anthropometry .......... ...................... 3 2. Flame Resistant CB Overgarment Test...participants (TPs) during this evaluation. Basic anthropometry of these subjects is given in Table I. TABLE 1 Basic Anthropometry Mean SD Maximum...5 S H L XL 39 H L XL XXL 43 L XL XXL XXL The areas considered were ease of doffing and donning, compatibility with prescribed clothing and field

External Resistances Applied to MFC Affect Core Microbiome and Swine Manure Treatment Efficiencies

PubMed Central

Vilajeliu-Pons, Anna; Bañeras, Lluis; Puig, Sebastià; Molognoni, Daniele; Vilà-Rovira, Albert; Hernández-del Amo, Elena; Balaguer, Maria D.; Colprim, Jesús

2016-01-01

Microbial fuel cells (MFCs) can be designed to combine water treatment with concomitant electricity production. Animal manure treatment has been poorly explored using MFCs, and its implementation at full-scale primarily relies on the bacterial distribution and activity within the treatment cell. This study reports the bacterial community changes at four positions within the anode of two almost identically operated MFCs fed swine manure. Changes in the microbiome structure are described according to the MFC fluid dynamics and the application of a maximum power point tracking system (MPPT) compared to a fixed resistance system (Ref-MFC). Both external resistance and cell hydrodynamics are thought to heavily influence MFC performance. The microbiome was characterised both quantitatively (qPCR) and qualitatively (454-pyrosequencing) by targeting bacterial 16S rRNA genes. The diversity of the microbial community in the MFC biofilm was reduced and differed from the influent swine manure. The adopted electric condition (MPPT vs fixed resistance) was more relevant than the fluid dynamics in shaping the MFC microbiome. MPPT control positively affected bacterial abundance and promoted the selection of putatively exoelectrogenic bacteria in the MFC core microbiome (Sedimentibacter sp. and gammaproteobacteria). These differences in the microbiome may be responsible for the two-fold increase in power production achieved by the MPPT-MFC compared to the Ref-MFC. PMID:27701451

AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo

PubMed Central

Unnikrishnan, A; Vo, A N Q; Pickford, R; Raftery, M J; Nunez, A C; Verma, A; Hesson, L B; Pimanda, J E

2018-01-01

The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material. We report that although AZA induces DNA demethylation in a dose-dependent manner, it has no corresponding effect on RNA methylation. By applying AZA-MS to primary bone marrow samples from patients undergoing AZA therapy, we have identified that responders accumulate more 5-AZA-CdR in their DNA compared with nonresponders. AZA resistance was not a result of impaired AZA metabolism or intracellular accumulation. Furthermore, AZA-MS has helped to uncover different modes of AZA resistance. Whereas some nonresponders fail to incorporate sufficient 5-AZA-CdR into DNA, others incorporate 5-AZA-CdR and effect DNA demethylation like AZA responders, but show no clinical benefit. PMID:29249821

Co-percolation to tune conductive behaviour in dynamical metallic nanowire networks.

PubMed

Fairfield, J A; Rocha, C G; O'Callaghan, C; Ferreira, M S; Boland, J J

2016-11-03

Nanowire networks act as self-healing smart materials, whose sheet resistance can be tuned via an externally applied voltage stimulus. This memristive response occurs due to modification of junction resistances to form a connectivity path across the lowest barrier junctions in the network. While most network studies have been performed on expensive noble metal nanowires like silver, networks of inexpensive nickel nanowires with a nickel oxide coating can also demonstrate resistive switching, a common feature of metal oxides with filamentary conduction. However, networks made from solely nickel nanowires have high operation voltages which prohibit large-scale material applications. Here we show, using both experiment and simulation, that a heterogeneous network of nickel and silver nanowires allows optimization of the activation voltage, as well as tuning of the conduction behavior to be either resistive switching, memristive, or a combination of both. Small percentages of silver nanowires, below the percolation threshold, induce these changes in electrical behaviour, even for low area coverage and hence very transparent films. Silver nanowires act as current concentrators, amplifying conductivity locally as shown in our computational dynamical activation framework for networks of junctions. These results demonstrate that a heterogeneous nanowire network can act as a cost-effective adaptive material with minimal use of noble metal nanowires, without losing memristive behaviour that is essential for smart sensing and neuromorphic applications.

Investigation and optimization of low-frequency noise performance in readout electronics of dc superconducting quantum interference device

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

Zhao, Jing; Peter Grünberg Institute; Zhang, Yi

2014-05-15

We investigated and optimized the low-frequency noise characteristics of a preamplifier used for readout of direct current superconducting quantum interference devices (SQUIDs). When the SQUID output was detected directly using a room-temperature low-voltage-noise preamplifier, the low-frequency noise of a SQUID system was found to be dominated by the input current noise of the preamplifiers in case of a large dynamic resistance of the SQUID. To reduce the current noise of the preamplifier in the low-frequency range, we investigated the dependence of total preamplifier noise on the collector current and source resistance. When the collector current was decreased from 8.4 mAmore » to 3 mA in the preamplifier made of 3 parallel SSM2220 transistor pairs, the low-frequency total voltage noise of the preamplifier (at 0.1 Hz) decreased by about 3 times for a source resistance of 30 Ω whereas the white noise level remained nearly unchanged. Since the relative contribution of preamplifier's input voltage and current noise is different depending on the dynamic resistance or flux-to-voltage transfer of the SQUID, the results showed that the total noise of a SQUID system at low-frequency range can be improved significantly by optimizing the preamplifier circuit parameters, mainly the collector current in case of low-noise bipolar transistor pairs.« less

Investigation and optimization of low-frequency noise performance in readout electronics of dc superconducting quantum interference device

NASA Astrophysics Data System (ADS)

Zhao, Jing; Zhang, Yi; Lee, Yong-Ho; Krause, Hans-Joachim

2014-05-01

We investigated and optimized the low-frequency noise characteristics of a preamplifier used for readout of direct current superconducting quantum interference devices (SQUIDs). When the SQUID output was detected directly using a room-temperature low-voltage-noise preamplifier, the low-frequency noise of a SQUID system was found to be dominated by the input current noise of the preamplifiers in case of a large dynamic resistance of the SQUID. To reduce the current noise of the preamplifier in the low-frequency range, we investigated the dependence of total preamplifier noise on the collector current and source resistance. When the collector current was decreased from 8.4 mA to 3 mA in the preamplifier made of 3 parallel SSM2220 transistor pairs, the low-frequency total voltage noise of the preamplifier (at 0.1 Hz) decreased by about 3 times for a source resistance of 30 Ω whereas the white noise level remained nearly unchanged. Since the relative contribution of preamplifier's input voltage and current noise is different depending on the dynamic resistance or flux-to-voltage transfer of the SQUID, the results showed that the total noise of a SQUID system at low-frequency range can be improved significantly by optimizing the preamplifier circuit parameters, mainly the collector current in case of low-noise bipolar transistor pairs.

Quantifying shallow subsurface water and heat dynamics using coupled hydrological-thermal-geophysical inversion

DOE PAGES

Tran, Anh Phuong; Dafflon, Baptiste; Hubbard, Susan S.; ...

2016-04-25

Improving our ability to estimate the parameters that control water and heat fluxes in the shallow subsurface is particularly important due to their strong control on recharge, evaporation and biogeochemical processes. The objectives of this study are to develop and test a new inversion scheme to simultaneously estimate subsurface hydrological, thermal and petrophysical parameters using hydrological, thermal and electrical resistivity tomography (ERT) data. The inversion scheme-which is based on a nonisothermal, multiphase hydrological model-provides the desired subsurface property estimates in high spatiotemporal resolution. A particularly novel aspect of the inversion scheme is the explicit incorporation of the dependence of themore » subsurface electrical resistivity on both moisture and temperature. The scheme was applied to synthetic case studies, as well as to real datasets that were autonomously collected at a biogeochemical field study site in Rifle, Colorado. At the Rifle site, the coupled hydrological-thermal-geophysical inversion approach well predicted the matric potential, temperature and apparent resistivity with the Nash-Sutcliffe efficiency criterion greater than 0.92. Synthetic studies found that neglecting the subsurface temperature variability, and its effect on the electrical resistivity in the hydrogeophysical inversion, may lead to an incorrect estimation of the hydrological parameters. The approach is expected to be especially useful for the increasing number of studies that are taking advantage of autonomously collected ERT and soil measurements to explore complex terrestrial system dynamics.« less

The impact of active site mutations of South African HIV PR on drug resistance: Insight from molecular dynamics simulations, binding free energy and per-residue footprints.

PubMed

Ahmed, Shaimaa M; Maguire, Glenn E M; Kruger, Hendrik G; Govender, Thirumala

2014-04-01

Molecular dynamics simulations and binding free energy calculations were used to provide an understanding of the impact of active site drug-resistant mutations of the South African HIV protease subtype C (C-SA HIV PR), V82A and V82F/I84V on drug resistance. Unique per-residue interaction energy 'footprints' were developed to map the overall drug-binding profiles for the wild type and mutants. Results confirmed that these mutations altered the overall binding landscape of the amino acid residues not only in the active site region but also in the flaps as well. Four FDA-approved drugs were investigated in this study; these include ritonavir (RTV), saquinavir (SQV), indinavir (IDV), and nelfinavir (NFV). Computational results compared against experimental findings were found to be complementary. Against the V82F/I84V variant, saquinavir, indinavir, and nelfinavir lose remarkable entropic contributions relative to both wild-type and V82A C-SA HIV PRs. The per-residue energy 'footprints' and the analysis of ligand-receptor interactions for the drug complexes with the wild type and mutants have also highlighted the nature of drug interactions. The data presented in this study will prove useful in the design of more potent inhibitors effective against drug-resistant HIV strains. © 2013 John Wiley & Sons A/S.

Soil types influence the fate of antibiotic-resistant bacteria and antibiotic resistance genes following the land application of sludge composts.

PubMed

Zhang, Junya; Sui, Qianwen; Tong, Juan; Zhong, Hui; Wang, Yawei; Chen, Meixue; Wei, Yuansong

2018-05-21

Sewage sludge was generally considered a significant reservoir of antibiotic resistance genes (ARGs) and could enter agricultural systems as fertilizer after composting. Soil types and the discrepancy of sludge composts could have influenced the fate of antibiotic-resistant bacteria (ARB) following the land application of sludge composts, which deserved to be clarified. Thus, the fate of ARB and ARGs following the land application of three types of sludge composts (A, B, and C) to three different soils (red soil, loess, and black soil) was investigated. The results showed that tetX, which was enriched the most during composting, did not affect the soil resistome, whereas tetG did. Soil types influenced the dynamics of ARB and ARGs significantly, whereas no significant difference was observed among compost types. The advantage of reducing ARGs during the composting process in compost B did not extend to land application. Land application of composts influenced the microbial community significantly at the early stage, but the microbial community returned to the control pattern gradually. Changes in the microbial community contributed more to the dynamics of ARGs in red and black soil compared with other factors, including co-selection from heavy metals, horizontal gene transfer, biomass and environmental factors, whereas horizontal gene transfer, reflected by intI1 levels, contributed the most in loess. Copyright © 2018 Elsevier Ltd. All rights reserved.

Population Genetics Study of Isoniazid Resistance Mutations and Evolution of Multidrug-Resistant Mycobacterium tuberculosis†

PubMed Central

Hazbón, Manzour Hernando; Brimacombe, Michael; Bobadilla del Valle, Miriam; Cavatore, Magali; Guerrero, Marta Inírida; Varma-Basil, Mandira; Billman-Jacobe, Helen; Lavender, Caroline; Fyfe, Janet; García-García, Lourdes; León, Clara Inés; Bose, Mridula; Chaves, Fernando; Murray, Megan; Eisenach, Kathleen D.; Sifuentes-Osornio, José; Cave, M. Donald; Ponce de León, Alfredo; Alland, David

2006-01-01

The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. PMID:16870753

Challenges with gonorrhea in the era of multi-drug and extensively drug resistance – are we on the right track?

PubMed Central

Unemo, Magnus; Golparian, Daniel; Shafer, William M

2015-01-01

Neisseria gonorrhoeae has retained antimicrobial resistance to drugs previously recommended for first-line empiric treatment of gonorrhea, and resistance to ceftriaxone, the last option for monotherapy, is evolving. Crucial actions to combat this developing situation include implementing response plans; considering use of dual antimicrobial regimens; enhancing surveillance of gonorrhea, gonococcal antimicrobial resistance, treatment failures and antimicrobial use/misuse and improving prevention, early diagnosis, contact tracing and treatment. The ways forward also include an intensified research to identify novel antimicrobial resistance determinants and develop and evaluate appropriate use of molecular antimicrobial resistance testing, ideally point-of-care and with simultaneous detection of gonococci, to supplement culture-based methods and ideally guide tailored treatment. It is crucial with an enhanced understanding of the dynamics of the national and international emergence, transmission and evolution of antimicrobial-resistant gonococcal strains. Genome sequencing combined with epidemiological metadata will detail these issues and might also revolutionize the molecular antimicrobial resistance testing. Ultimately, novel antimicrobials are essential and some antimicrobials in development have shown potent in vitro activity against gonococci. Several of these antimicrobials deserve further attention for potential future treatment of gonorrhea. PMID:24702589