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Sample records for dynamic conformal arc

  1. Comparison of volumetric-modulated arc therapy and dynamic conformal arc treatment planning for cranial stereotactic radiosurgery.

    Science.gov (United States)

    Molinier, Jessica; Kerr, Christine; Simeon, Sebastien; Ailleres, Norbert; Charissoux, Marie; Azria, David; Fenoglietto, Pascal

    2016-01-08

    The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10° table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 ± 0.05) compared with DCA procedure (0.27± 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 ± 0.04) compared with those obtained with the DCA technique (0.77 ± 0.05). DCA improved healthy brain protection (8.35 ± 5.61 cc vs. 10.52 ± 6.40 cc for RANC) and reduced monitor unit numbers (3046 ± 374 MU vs. 4651 ± 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 ± 0.07). The CI was improved with RAT (0.8 ± 0.08 for RAT vs. 0.71 ± 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 ± 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 ± 0.03 vs. 0.53 ± 0.2 for DCA) and conformity (0.72± 0.06vs. 0.56 ± 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 ± 1.05Gyvs. 14.12 ± 0.59 Gy for DCA, and Dmean = 3.96 ± 3.57Gyvs. 4.72 ± 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 ± 190 MUvs. 3438 ± 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA

  2. Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Xin Ming

    Full Text Available To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT, intensity-modulated radiotherapy (IMRT, or volumetric modulated arc therapy (VMAT at our institution in the past seven years.A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated.The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2% with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance.Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin's disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy.

  3. Dosimetric comparison of helical tomotherapy and dynamic conformal arc therapy in stereotactic radiosurgery for vestibular schwannomas.

    Science.gov (United States)

    Lee, Tsair-Fwu; Chao, Pei-Ju; Wang, Chang-Yu; Lan, Jen-Hong; Huang, Yu-Je; Hsu, Hsuan-Chih; Sung, Chieh-Cheng; Su, Te-Jen; Lian, Shi-Long; Fang, Fu-Min

    2011-01-01

    The dosimetric results of stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) performed using dynamic conformal arc therapy (DCAT) with the Novalis system and helical TomoTherapy (HT) were compared using plan quality indices. The HT plans were created for 10 consecutive patients with VS previously treated with SRS using the Novalis system. The dosimetric indices used to compare the techniques included the conformity index (CI) and homogeneity index (HI) for the planned target volume (PTV), the comprehensive quality index (CQI) for nine organs at risk (OARs), gradient score index (GSI) for the dose drop-off outside the PTV, and plan quality index (PQI), which was verified using the plan quality discerning power (PQDP) to incorporate 3 plan indices, to evaluate the rival plans. The PTV ranged from 0.27-19.99 cm(3) (median 3.39 cm(3)), with minimum required PTV prescribed doses of 10-16 Gy (median 12 Gy). Both systems satisfied the minimum required PTV prescription doses. HT conformed better to the PTV (CI: 1.51 ± 0.23 vs. 1.94 ± 0.34; p < 0.01), but had a worse drop-off outside the PTV (GSI: 40.3 ± 10.9 vs. 64.9 ± 13.6; p < 0.01) compared with DCAT. No significant difference in PTV homogeneity was observed (HI: 1.08 ± 0.03 vs. 1.09 ± 0.02; p = 0.20). HT had a significantly lower maximum dose in 4 OARs and significant lower mean dose in 1 OAR; by contrast, DCAT had a significantly lower maximum dose in 1 OAR and significant lower mean dose in 2 OARs, with the CQI of the 9 OARs = 0.92 ± 0.45. Plan analysis using PQI (HT 0.37 ± 0.12 vs. DCAT 0.65 ± 0.08; p < 0.01), and verified using the PQDP, confirmed the dosimetric advantage of HT. However, the HT system had a longer beam-on time (33.2 ± 7.4 vs. 4.6 ± 0.9 min; p < 0.01) and consumed more monitor units (16772 ± 3803 vs. 1776 ± 356.3; p < 0.01). HT had a better dose conformity and similar dose homogeneity but worse dose gradient than DCAT. Plan analysis confirmed the dosimetric advantage of HT

  4. Implementation and evaluation of modified dynamic conformal arc (MDCA) technique for lung SBRT patients following RTOG protocols

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Chengyu, E-mail: shicy1974@gmail.com [St. Vincent' s Medical Center, Bridgeport, CT (United States); Tazi, Adam; Fang, Deborah Xiangdong; Iannuzzi, Christopher [St. Vincent' s Medical Center, Bridgeport, CT (United States)

    2013-10-01

    To implement modified dynamic conformal arc (MDCA) technique and Radiation Therapy Oncology Group (RTOG) protocols in our clinic for stereotactic body radiation therapy (SBRT) treatment of patients with Stage I/II non–small cell lung cancer. Five patients with non–small cell lung cancer have been treated with SBRT. All the patients were immobilized using CIVCO Body Pro-Lok system and scanned using GE 4-slice computed tomography. The MDCA technique that was previously published was adopted as our planning technique, and RTOG protocols for the lung SBRT were followed. The patients were treated on Novalis Tx system with cone-beam computed tomography imaging guidance. All the patient plans passed the RTOG criteria. The conformal index ranges from 0.99 to 1.12 for the planning target volume, and the biological equivalent dose for the planning target volume is overall 100 Gy. Critical structures (lung, spinal cord, brachial plexus, skin, and chest wall) also meet RTOG protocols or published data. A 6-month follow-up of one of the patients shows good local disease control. We have successfully implemented the MDCA technique into our clinic for the lung SBRT program. It shows that the MDCA is useful and efficient for the lung SBRT planning, with the plan quality meeting the RTOG protocols.

  5. HybridArc: A novel radiation therapy technique combining optimized dynamic arcs and intensity modulation

    Energy Technology Data Exchange (ETDEWEB)

    Robar, James L., E-mail: james.robar@cdha.nshealth.ca [Department of Radiation Oncology, Dalhousie University, Halifax (Canada); Department of Physics and Atmospheric Science, Dalhousie University, Halifax (Canada); Thomas, Christopher [Department of Radiation Oncology, Dalhousie University, Halifax (Canada)

    2012-01-01

    This investigation focuses on possible dosimetric and efficiency advantages of HybridArc-a novel treatment planning approach combining optimized dynamic arcs with intensity-modulated radiation therapy (IMRT) beams. Application of this technique to two disparate sites, complex cranial tumors, and prostate was examined. HybridArc plans were compared with either dynamic conformal arc (DCA) or IMRT plans to determine whether HybridArc offers a synergy through combination of these 2 techniques. Plans were compared with regard to target volume dose conformity, target volume dose homogeneity, sparing of proximal organs at risk, normal tissue sparing, and monitor unit (MU) efficiency. For cranial cases, HybridArc produced significantly improved dose conformity compared with both DCA and IMRT but did not improve sparing of the brainstem or optic chiasm. For prostate cases, conformity was improved compared with DCA but not IMRT. Compared with IMRT, the dose homogeneity in the planning target volume was improved, and the maximum doses received by the bladder and rectum were reduced. Both arc-based techniques distribute peripheral dose over larger volumes of normal tissue compared with IMRT, whereas HybridArc involved slightly greater volumes of normal tissues compared with DCA. Compared with IMRT, cranial cases required 38% more MUs, whereas for prostate cases, MUs were reduced by 7%. For cranial cases, HybridArc improves dose conformity to the target. For prostate cases, dose conformity and homogeneity are improved compared with DCA and IMRT, respectively. Compared with IMRT, whether required MUs increase or decrease with HybridArc was site-dependent.

  6. Conformal fluid dynamics

    CERN Document Server

    Jarvis, P D

    2006-01-01

    We present a conformal theory of a dissipationless relativistic fluid in 2 space-time dimensions. The theory carries with it a representation of the algebra of 2-$D$ area-preserving diffeomorphisms in the target space of the complex scalar potentials. A complete canonical description is given, and the central charge of the current algebra is calculated. The passage to the quantum theory is discussed in some detail; as a result of operator ordering problems, full quantization at the level of the fields is as yet an open problem.

  7. Generative models of conformational dynamics.

    Science.gov (United States)

    Langmead, Christopher James

    2014-01-01

    Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term 'generative' refers to a model of the joint probability distribution over the behaviors of the constituent atoms. In the context of molecular modeling, generative models reveal the correlation structure between the atoms, and may be used to predict how the system will respond to structural perturbations. We begin by discussing traditional methods, which produce multivariate Gaussian models. We then discuss GAMELAN (GRAPHICAL MODELS OF ENERGY LANDSCAPES), which produces generative models of complex, non-Gaussian conformational dynamics (e.g., allostery, binding, folding, etc.) from long timescale simulation data.

  8. Conformal dynamical equivalence and applications

    Science.gov (United States)

    Spyrou, N. K.

    2011-02-01

    The "Conformal Dynamical Equivalence" (CDE) approach is briefly reviewed, and some of its applications, at various astrophysical levels (Sun, Solar System, Stars, Galaxies, Clusters of Galaxies, Universe as a whole), are presented. According to the CDE approach, in both the Newtonian and general-relativistic theories of gravity, the isentropic hydrodynamic flows in the interior of a bounded gravitating perfect-fluid source are dynamically equivalent to geodesic motions in a virtual, fully defined fluid source. Equivalently, the equations of hydrodynamic motion in the former source are functionally similar to those of the geodesic motions in the latter, physically, fully defined source. The CDE approach is followed for the dynamical description of the motions in the fluid source. After an observational introduction, taking into account all the internal physical characteristics of the corresponding perfect-fluid source, and based on the property of the isentropic hydrodynamic flows (quite reasonable for an isolated physical system), we examine a number of issues, namely, (i) the classical Newtonian explanation of the celebrated Pioneer-Anomaly effect in the Solar System, (ii) the possibility of both the attractive gravity and the repulsive gravity in a non-quantum Newtonian framework, (iii) the evaluation of the masses - theoretical, dynamical, and missing - and of the linear dimensions of non-magnetized and magnetized large-scale cosmological structures, (iv) the explanation of the flat-rotation curves of disc galaxies, (v) possible formation mechanisms of winds and jets, and (vi) a brief presentation of a conventional approach - toy model to the dynamics of the Universe, characterized by the dominant collisional dark matter (with its subdominant luminous baryonic "contamination"), correctly interpreting the cosmological observational data without the need of the notions dark energy, cosmological constant, and universal accelerating expansion.

  9. SU-C-BRB-05: Investigation of Conformal Arc Therapy Utilizing Newly Designed Cobalt 60 Machine

    Energy Technology Data Exchange (ETDEWEB)

    Eldib, A [Fox Chase Cancer Center, Philadelphia, PA (United States); Department of Physics, AlAzhar University, Cairo (Egypt); Chibani, O; Jin, L; Li, J; Veltchev, I; Price, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States); Mora, G [Universidade de Lisboa, Codex, Lisboa (Portugal)

    2015-06-15

    Purpose: A new modernized design for cobalt 60 (Co-60) machines is being developed with a ring type gantry. In this study we investigate the beneficial outcome of the new design for conformal arc therapy for various clinical sites. The new modality was evaluated based on isodose distributions and dose volume histograms as compared to 6MV photon beams from conventional linear accelerators. Methods: Computed tomographic images of seven different SBRT patients were selected from our patient database. All of these cases were previously planned on the Eclipse treatment planning system. New plans for these patients were generated with a modified conformal arc technique using both 6MV and Co-60 beams. The conformal arc was created by the delivery of treatment fields conformal to the target cross-section at every 5 or 10 degrees. The field shape was modified or turned off when it initially passed through a critical structure. Monte Carlo codes, MCBEAM and MCPLAN, were used for the machine head simulation and phantom/patient dose calculation, respectively. In the new Co-60 machine design, the source-to-isocenter distance was 60cm and the treatment head included the Co-60 source, primary collimator, jaws and MLC. Results: For all cases investigated, conformal arc plans utilizing Co-60 beams achieved similar conformity (mean conformity index=1.19) comparing to 6MV photon beams. Isodose distributions were tailored similarly around the PTV; both Co-60 and 6MV plans met our clinical acceptance criteria for the target coverage, and the maximum and minimum target doses. The DVH for the Co-60 plans showed slightly lower doses to the critical structures although the differences were small in most cases. Conclusion: There were no significant dosimetric differences between 6MV and Co-60 plans. Our results confirmed that this new Co-60 design could be a cost-effective machine for advanced radiotherapy due to its low cost, low maintenance and high up time.

  10. On the stochastic dynamics of molecular conformation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    An important functioning mechanism of biological macromolecules is the transition between different conformed states due to thermal fluctuation. In the present paper, a biological macromolecule is modeled as two strands with side chains facing each other, and its stochastic dynamics including the statistics of stationary motion and the statistics of conformational transition is studied by using the stochastic averaging method for quasi Hamiltonian systems. The theoretical results are confirmed with the results from Monte Carlo simulation.

  11. SU-E-T-538: Lung SBRT Dosimetric Comparison of 3D Conformal and RapidArc Planning

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, R; Zhan, L; Osei, E [Grand River Hospital, Kitchener, ON (Canada)

    2015-06-15

    Purpose: Dose distributions of RapidArc Plan can be quite different from standard 3D conformal radiation therapy. SBRT plans can be optimized with high conformity or mimic the 3D conformal treatment planning with very high dose in the center of the tumor. This study quantifies the dosimetric differences among 3D conformal plan; flattened beam and FFF beam RapidArc Plans for lung SBRT. Methods: Five lung cancer patients treated with 3D non-coplanar SBRT were randomly selected. All the patients were CT scanned with 4DCT to determine the internal target volume. Abdominal compression was applied to minimize respiratory motion for SBRT patients. The prescription dose was 48 Gy in 4 fractions. The PTV coverage was optimized by two groups of objective function: one with high conformity, another mimicking 3D conformal dose distribution with high dose in the center of PTV. Optimization constraints were set to meet the criteria of the RTOG-0915 protocol. All VMAT plans were optimized with the RapidArc technique using four full arcs in Eclipse treatment planning system. The RapidArc SBRT plans with flattened 6MV beam and 6MV FFF beam were generated and dosimetric results were compared with the previous treated 3D non-coplanar plans. Results: All the RapidArc plans with flattened beam and FFF beam had similar results for the PTV and OARs. For the high conformity optimization group, The DVH of PTV exhibited a steep dose fall-off outside the PTV compared to the 3D non-coplanar plan. However, for the group mimicking the 3D conformal target dose distribution, although the PTV is very similar to the 3D conformal plan, the ITV coverage is better than 3D conformal plan. Conclusion: Due to excellent clinical experiences of 3D conformal SBRT treatment, the Rapid Arc optimization mimicking 3D conformal planning may be suggested for clinical use.

  12. A novel conformal arc technique for postoperative whole pelvic radiotherapy for endometrial cancer.

    Science.gov (United States)

    Yang, Ruijie; Jiang, Weijuan; Wang, Junjie

    2009-12-01

    Conventional whole pelvic radiotherapy (WPRT) with 3-dimensional conformal radiotherapy (3D-CRT) exposes most of the contents of the true pelvis to the prescribed dose. Intensity-modulated radiation therapy (IMRT) provides more conformal dose distribution and better sparing of critical structures for WPRT. However, IMRT is more complicated in planning and delivery, requiring more expensive equipment and time-consuming quality assurance. We explore and evaluate a novel conformal arc radiotherapeutic technique for postoperative WPRT for endometrial cancer in this study. This technique involves 2-axis conformal arc therapy (2A-CAT) with 180-degree rotation around 2 isocenters each in 2 separate dose-shaping structures. Dosimetric comparison with 3D-CRT and IMRT for 10 endometrial cancer patients undergoing postoperative WPRT was performed to evaluate this new 2A-CAT technique. The mean conformity indices were 0.83, 0.61, and 0.88 for 2A-CAT, 3D-CRT, and IMRT, respectively. The mean homogeneity indices were 1.15, 1.08, and 1.10. The mean doses to bowel, rectum, bladder, and pelvic bone marrow were, respectively, 1.19, 3.39, 4.65, and 1.64 Gy lower with 2A-CAT than with 3D-CRT (P endometrial cancer, 2A-CAT significantly improves the dose conformity and sparing of bowel, rectum, and bladder compared with 3D-CRT. Despite dose uniformity and conformity being still inferior to those of IMRT, its simplicity and extensive availability combined with further improvement warrant it as a potential shortcut alternative to IMRT.

  13. Radiosurgery of small skull-base lesions. No advantage for intensity-modulated stereotactic radiosurgery versus conformal arc technique

    Energy Technology Data Exchange (ETDEWEB)

    Ernst-Stecken, A.; Sauer, R.; Grabenbauer, G. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center, Univ. of Erlangen-Nuremberg, Erlangen (Germany); Lambrecht, U.; Mueller, R. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center, Univ. of Erlangen-Nuremberg, Erlangen (Germany); Div. of Medical Physics, Dept. of Radiation Therapy, Univ. of Erlangen-Nuremberg, Erlangen (Germany); Ganslandt, O.; Fahlbusch, R. [Dept. of Neurosurgery, Univ. of Erlangen-Nuremberg, Erlangen (Germany)

    2005-05-01

    Background and purpose: intensity-modulated stereotactic radiotherapy (IMSRT) has shown the ability to conform the dose to concavities and to better avoid critical organs for large tumors. Given the availability of an electronically driven micro-multileaf collimator, both intensity-modulated stereotactic radiosurgery (IMSRS) and dynamic conformal arc (DCA) technique (DCA) can be performed at the Novalis Shaped Beam Surgery Center, University of Erlangen-Nuremberg, Germany, since 12/2002. This study evaluates both techniques in small skull-base tumors treated with radiosurgery. Material and methods: between 12/2002 and 04/2004, a total of 109 radiosurgical procedures were performed in 77 patients, equally distributed between patients with acoustic neuroma (AN), pituitary adenoma (PA) and meningeoma (M). Six index patients (n = 2 AN, n = 1 PA, n = 3 M) routinely planned for dynamic arc stereotactic radiosurgery were replanned using the IMSRS approach (BrainScan, BrainLAB, Heimstetten, Germany). The RTOG radiosurgery quality assurance guidelines, isodose volumes, doses to organs at risk (OAR), and dose delivery criteria were compared. Results: DCA was superior to IMSRS for homogeneity and coverage. IMSRS could keep the high-dose-irradiated volumes (90% isodose volume) lower than DCA in the PA and AN with very small volumes, but all other lower dose volumes were larger for IMSRS. Dose maxima to OAR were higher for IMSRS. Treatment delivery time for IMSRS would clearly exceed treatment time for DCA by a factor of 2-3. The integral absorbed dose to the brain was much higher in the IMSRS than in the DCA approach (factor 2-3). Conclusion: RTOG radiosurgery guidelines were best met by the DCA rather than IMSRS approach for the treatment of small skull-base lesions. The IMSRS approach will increase the time for planning, dose delivery and integral dose to the brain. Thus, IMSRT techniques are recommended for fractionated stereotactic radiotherapy to larger volumes rather

  14. CHEP2015: Dynamic Resource Allocation with arcControlTower

    CERN Document Server

    Filipcic, Andrej; The ATLAS collaboration; Nilsen, Jon Kerr

    2015-01-01

    Distributed computing resources available for high-energy physics research are becoming less dedicated to one type of workflow and researchers’ workloads are increasingly exploiting modern computing technologies such as parallelism. The current pilot job management model used by many experiments relies on static dedicated resources and cannot easily adapt to these changes. The model used for ATLAS in Nordic countries and some other places enables a flexible job management system based on dynamic resources allocation. Rather than a fixed set of resources managed centrally, the model allows resources to be requested on the fly. The ARC Computing Element (ARC-CE) and ARC Control Tower (aCT) are the key components of the model. The aCT requests jobs from the ATLAS job mangement system (Panda) and submits a fully-formed job description to ARC-CEs. ARC-CE can then dynamically request the required resources from the underlying batch system. In this paper we describe the architecture of the model and the experience...

  15. Dynamic Resource Allocation with the arcControlTower

    CERN Document Server

    Filipcic, Andrej; The ATLAS collaboration; Nilsen, Jon Kerr

    2015-01-01

    Distributed computing resources available for high-energy physics research are becoming less dedicated to one type of workflow and researchers’ workloads are increasingly exploiting modern computing technologies such as parallelism. The current pilot job management model used by many experiments relies on static dedicated resources and cannot easily adapt to these changes. The model used for ATLAS in Nordic countries and some other places enables a flexible job management system based on dynamic resources allocation. Rather than a fixed set of resources managed centrally, the model allows resources to be requested on the fly. The ARC Computing Element (ARC-CE) and ARC Control Tower (aCT) are the key components of the model. The aCT requests jobs from the ATLAS job management system (PanDA) and submits a fully-formed job description to ARC-CEs. ARC-CE can then dynamically request the required resources from the underlying batch system. In this paper we describe the architecture of the model and the experienc...

  16. Analysis of low energy arc discharge characteristics based on dynamic V-A characteristics model

    Institute of Scientific and Technical Information of China (English)

    JING Li-nan; WANG Li-gong

    2006-01-01

    Low energy arc discharge characteristics was analyzed based on dynamic V-A characteristics model. It draws conclusions that discharge time relates to the source voltage and the product of inductance and stable current, discharge time will increase when the source voltage increases; current reduce rate is in inverse proportion to the value of inductance; arc resistance when the arc occurs is the ratio of minimum arcing voltage to stable current. It also gains the expressions of arc resistance and arc power, arc resistance and arc power both increase as the source voltage increases and decrease as the value of inductance increases. Conclusions above mentioned are helpful to design intrinsically safe circuits.

  17. SU-E-T-262: Development of An In-House Forward Planning System for Conformal Arc Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eldib, A [Fox Chase Cancer Center, Philadelphia, PA (United States); Department of Physics, AlAzhar University, Cairo (Egypt); Chibani, O; Jin, L; Li, J; Chen, L; Lin, T; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States); Lin, M [University of Maryland School of Medicine, Baltimore, MD (United States)

    2015-06-15

    Purpose: Conformal radiotherapy with forward planning has many practical advantages (e.g., more uniform target dose) and has been used routinely for stereotactic body radiation therapy (SBRT) and other conventional treatment. This study investigates a forward-planning approach for conformal arc therapy and a dedicated treatment planning system (TPS) for a newly designed cobalt 60 machine with a ring type gantry and a multileaf collimator (MLC). Methods: Conformal arcs were modeled with continuous delivery of treatment fields conformal to the target cross-section. Treatment plans were further optimized by weighting or offsetting beams based on the target-critical structure relationship. CT and structure data of seven previous SBRT patients treated at our center were used for plan evaluation. An in-house forward planning tool was developed to aid the forward planning process. A graphical user interface (GUI) was designed with interactive and automatic adjustment between beam gantry angle and the beam weight. Dose distributions were calculated using our in-house Monte Carlo based TPS. Dose contributions from individual beam angles were summed together with different weight factors, which were continuously optimized until the pre-set dose conformity goal was met. Results: We were able to achieve target coverage and critical structure sparing to meet the required clinical criteria in all studied cases. It should be mentioned that those cases were selected having critical structures not proximal to the target. However, this was usually the case in the majority of SBRT cases especially those involving lung targets. The developed GUI tool was very useful in the forward treatment planning process. Conclusion: Conformal arcs can be used successfully on the new Cobalt 60 modality for the treatment of a sizeable fraction of cancer patients, which can be efficiently planned with our simple forward planning approach.

  18. Dynamics in the Charged Time Conformal Schwarzschild Black Hole

    CERN Document Server

    Jawad, Abdul; Shahzad, M Umair; Abbas, G

    2016-01-01

    In this work, we present the new technique for discussing the dynamical motion of neutral as well as charged particles in the absence/presence of magnetic field around the time conformal Schwarzschild black hole. Initially, we find the numerical solutions of geodesics of Schwarzschild black hole and the time conformal Schwarzschild black hole. We observe that the Schwarzschild spacetime admits the time conformal factor $e^{\\epsilon f(t)}$, where $f(t)$ is an arbitrary function and $\\epsilon$ is very small which causes the perturbation in the spacetimes. This technique also re-scale the energy content of spacetime. We also investigate the thermal stability, horizons and energy conditions corresponding time conformal Schwarzschild spacetime. Also, we examine the dynamics of neutral and charged particle around time conformal Schwarzschild black hole. We investigate the circumstances under which the particle can escape from vicinity of black hole after collision with another particle. We analyze the effective pot...

  19. Comparison of Rapid Arc and Intensity-modulated Radiotherapy Plans Using Unified Dosimetry Index and the Impact of Conformity Index on Unified Dosimetry Index Evaluation.

    Science.gov (United States)

    Krishnan, Jayapalan; Shetty, Jayarama; Rao, Suresh; Hegde, Sanath; Shambhavi, C

    2017-01-01

    The aim of this study was to evaluate the impact of conformity index in the unified dosimetry index (UDI) score for two different planning techniques namely intensity-modulated radiotherapy (IMRT) and Rapid Arc. Rapid Arc and IMRT plans of 57 patients were evaluated and compared using UDI score which incorporates four indices. To determine the impact of conformity index on the IMRT and Rapid Arc plans, UDI at conformity index one of all plan (UDIunit_CI) score was calculated by assuming conformity index is equal to one. Mean and standard deviations of all indices were calculated. Rapid Arc technique plans of different treatment sites of all patients scored lesser UDI than IMRT plans, and the conformity index of Rapid Arc plan was significantly better than IMRT plan. The average dose gradient, homogeneity, coverage, and conformity index of all sites with Rapid Arc plans were 0.212 ± 0.05, 1.123 ± 0.03, 0.959 ± 0.03, and 1.056 ± 0.09; with IMRT plans were 0.190 ± 0.05, 1.113 ± 0.04, 0.950 ± 0.04, and 1.172 ± 0.16, respectively. UDI score value with actual conformity index of Rapid Arc and IMRT plans differed significantly (P conformity index equal to one did not differ significantly (P = 0.528). In the comparison of IMRT and Rapid Arc plans using the UDI score, the impact of conformity index was significant.

  20. Effects of shielding gas composition on arc profile and molten pool dynamics in gas metal arc welding of steels

    Science.gov (United States)

    Wang, L. L.; Lu, F. G.; Wang, H. P.; Murphy, A. B.; Tang, X. H.

    2014-11-01

    In gas metal arc welding, gases of different compositions are used to produce an arc plasma, which heats and melts the workpiece. They also protect the workpiece from the influence of the air during the welding process. This paper models gas metal arc welding (GMAW) processes using an in-house simulation code. It investigates the effects of the gas composition on the temperature distribution in the arc and on the molten pool dynamics in gas metal arc welding of steels. Pure argon, pure CO2 and different mixtures of argon and CO2 are considered in the study. The model is validated by comparing the calculated weld profiles with physical weld measurements. The numerical calculations reveal that gas composition greatly affects the arc temperature profile, heat transfer to the workpiece, and consequently the weld dimension. As the CO2 content in the shielding gas increases, a more constricted arc plasma with higher energy density is generated as a result of the increased current density in the arc centre and increased Lorentz force. The calculation also shows that the heat transferred from the arc to the workpiece increases with increasing CO2 content, resulting in a wider and deeper weld pool and decreased reinforcement height.

  1. The Dynamics of the Neptunian ADAMS Ring's Arcs

    Science.gov (United States)

    Foryta, Dietmar W.; Sicardy, Bruno

    1996-09-01

    We examine the resonant forcing of a narrow ringlet by a nearby satellite on an inclined, but circular, orbit. The general techniques that we develop are used to study the dynamics of Neptune's ring arcs, near the 43:42 mean motion resonances with the satellite Galatea. More specifically, the averaged equations of motions are used to analyze the coupling between the various resonances at work, while a mapping integrator allows us to integrate the motion of up to 104particles for several centuries. We show that even in the absence of dissipation, the coupling between the horizontal and vertical motions of the particles can lead to a stochastic migration of the particles for one to the other of the 43 × 2 = 86 corotation sites where the arcs are assumed to be trapped. The pressure of solar radiation sweeps out from the arcs the particles with a ratio β_cdof pressure of radiation to solar gravitation larger than ∼0.01, corresponding to ∼50 μm-sized icy particles in the limit of geometrical optics. Poynting-Robertson (PR) drag, on the other hand, has only a small effect on dust particlesalreadyinside the corotation sites. In contrast, PR drag rapidly drives the particles lying outside these sites on unstable orbits. Inelastic collisions between the larger particles remain the most serious problem for the arc stability. We discuss the implications of these results in terms of a population of large particles being the source of dusty arcs. We show in particular that such structures, while not permanent, can be nevertheless statistically common at corotation resonances with a nearby satellite such as Galatea.

  2. Optimization of Conformational Dynamics in an Epistatic Evolutionary Trajectory.

    Science.gov (United States)

    González, Mariano M; Abriata, Luciano A; Tomatis, Pablo E; Vila, Alejandro J

    2016-07-01

    The understanding of protein evolution depends on the ability to relate the impact of mutations on molecular traits to organismal fitness. Biological activity and robustness have been regarded as important features in shaping protein evolutionary landscapes. Conformational dynamics, which is essential for protein function, has received little attention in the context of evolutionary analyses. Here we employ NMR spectroscopy, the chief experimental tool to describe protein dynamics at atomic level in solution at room temperature, to study the intrinsic dynamic features of a metallo- Β: -lactamase enzyme and three variants identified during a directed evolution experiment that led to an expanded substrate profile. We show that conformational dynamics in the catalytically relevant microsecond to millisecond timescale is optimized along the favored evolutionary trajectory. In addition, we observe that the effects of mutations on dynamics are epistatic. Mutation Gly262Ser introduces slow dynamics on several residues that surround the active site when introduced in the wild-type enzyme. Mutation Asn70Ser removes the slow dynamics observed for few residues of the wild-type enzyme, but increases the number of residues that undergo slow dynamics when introduced in the Gly262Ser mutant. These effects on dynamics correlate with the epistatic interaction between these two mutations on the bacterial phenotype. These findings indicate that conformational dynamics is an evolvable trait, and that proteins endowed with more dynamic active sites also display a larger potential for promoting evolution.

  3. Dynamical realization of l-conformal Galilei algebra and oscillators

    Energy Technology Data Exchange (ETDEWEB)

    Galajinsky, Anton, E-mail: galajin@mph.phtd.tpu.ru [Laboratory of Mathematical Physics, Tomsk Polytechnic University, 634050 Tomsk, Lenin Ave. 30 (Russian Federation); Masterov, Ivan, E-mail: masterov@mph.phtd.tpu.ru [Laboratory of Mathematical Physics, Tomsk Polytechnic University, 634050 Tomsk, Lenin Ave. 30 (Russian Federation)

    2013-01-11

    The method of nonlinear realizations is applied to the l-conformal Galilei algebra to construct a dynamical system without higher derivative terms in the equations of motion. A configuration space of the model involves coordinates, which parametrize particles in d spatial dimensions, and a conformal mode, which gives rise to an effective external field. It is shown that trajectories of the system can be mapped into those of a set of decoupled oscillators in d dimensions.

  4. A dosimetric evaluation of volumetric modulated arc therapy, intensity modulated radiation therapy, and three-dimensional conformal radiation therapy for the lower extremity soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sol Min; Song, Seong Chan; Hyun, Sung Eun; Park, Heung Deuk; Lee, Jaegi; Kim, Young Suk; Kim, Gwi Eon [Dept. of Radiation Oncology, Jeju National University Hospital, Jeju (Korea, Republic of)

    2016-06-15

    A dosimetric evaluation of volumetric modulated arc therapy, intensity modulated radiation therapy, and three-dimensional conformal radiation therapy for the lower extremity soft tissue sarcoma For the lower extremity soft tissue sarcoma, volumetric modulated arc therapy, intensity modulated radiation therapy, and three-dimensional conformal radiation therapy were evaluated to compare these three treatment planning technique. The mean doses to the planning target volume and the femur were calculated to evaluate target coverage and the risk of bone fracture during radiation therapy. Volumetric modulated arc therapy can reduce the dose to the femur without compromising target coverage and reduce the treatment time compared with intensity modulated radiation therapy.

  5. Dose comparison between three planing prostate: 3-D conformational radiotherapy, coplanar arc therapy and non-coplanar arc therapy; Comparaison dosimetrique de trois balistiques prostatiques: radiotherapie conformationnelle tridimensionnelle, arctherapie coplanaire et arctherapie non-coplanaire

    Energy Technology Data Exchange (ETDEWEB)

    Voyant, C.; Baadj, A.; Biffi, K.; Leschi, D.; Lantieri, C. [Centre Hospitalier Dept. Castelluccio, Service de Radiotherapie, Ajaccio (France); Voyant, C. [Universite de Corse, Lab. SPE, CNRS-UMR 6134, Corte (France)

    2008-09-15

    Purpose: Comparative study between a classical conformational prostate radiotherapy (3 D.R.T.C.) and two arc therapy techniques, a coplanar (A.T.-C) and the other non-coplanar (A.T.-N.C.). Patients and Methods:The comparison has been made retrospectively on 30 patients with localized prostate cancer (T.2-T.3a, P.S.A. < 20 ng/ml, Gleason < 7). The objective criteria for comparison were the N.T.C.P., E.U.D., and dose volume (on D.V.H.), for the volumes of bladder wall, rectal wall, femoral heads, small bowel, prostate (P) and seminal vesicles (V.S.). The treatment was 46 Gy on P.T.V.1 (V.S. + P + margins), and then an overdose of 30 Gy on P.T.V.1 (P + margins). Results: For prostate volumes exceeding 75 cm{sup 3}, arc therapy leads to a decrease in uniformity in the target volume and an increase in the dose received by the femoral heads, this method does not seem appropriate. For prostate volumes less than 75 cm{sup 3}, in addition to the coverage almost tumor, and radiation toxicity equivalent to the bladder and the small intestine, there is a significant increase in the dose to the femoral heads, while the remaining is still within limits, such as clinically tolerable. The contribution of arc therapy is mainly observed at the level of rectal doses. The dose received by 30% of the rectum is reduced by - 12% for A.T.-C and - 11.7% for A.T-N.C., and E.U.D. rectum - 5.2% and - 4.8%. Conclusion: In this virtual study, the arc therapy seems to generate a true dose reduction in the rectum wall. These results encourage us to continue the investigation for a possible integration in a dynamic clinical routine. (authors)

  6. Dosimetry Comparison between Volumetric Modulated Arc Therapy with RapidArc and Fixed Field Dynamic IMRT for Local-Regionally Advanced Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bao-min Zheng; Xiao-xia Dong; Hao Wu; You-jia Duan; Shu-kui Han; Yan Sun

    2011-01-01

    Objective:A dosimetric study was performed to evaluate the performance of volumetric modulated arc radiotherapy with RapidArc on locally advanced nasopharyngeal carcinoma (NPC).Methods:The CT scan data sets of 20 patients of locally advanced NPC were selected randomly.The plans were managed using volumetric modulated arc with RapidArc and fixed nine-field coplanar dynamic intensity-modulated radiotherapy (IMRT) for these patients.The dosimetry of the planning target volumes (PTV),the organs at risk (OARs) and the healthy tissue were evaluated.The dose prescription was set to 70 Gy to the primary tumor and 60 Gy to the clinical target volumes (CTV) in 33 fractions.Each fraction applied daily,five fractions per week.The monitor unit (MU) values and the delivery time were scored to evaluate the expected treatment efficiency.Results:Both techniques had reached clinical treatment's requirement.The mean dose (Dmean),maximum dose (Dmax) and minimum dose (Dmin) in RapidArc and fixed field IMRT for PTV were 68.4±0.6 Gy,74.8±0.9 Gy and 56.8±1.1 Gy; and 67.6±0.6 Gy,73.8±0.4 Gy and 57.5±0.6 Gy (P<0.05),respectively.Homogeneity index was 78.85±1.29 in RapidArc and 80.34±0.54 (P<0.05) in IMRT.The conformity index (CI:95%) was 0.78±0.01 for both techniques (P>0.05).Compared to IMRT,RapidArc allowed a reduction of Dmean to the brain stem,mandible and optic nerves of 14.1% (P<0.05),5.6% (P<0.05) and 12.2% (P<0.05),respectively.For the healthy tissue and the whole absorbed dose,Dmean of RapidArc was reduced by 3.6% (P<0.05),and 3.7% (P<0.05),respectively.The Dmean to the parotids,the spinal cord and the lens had no statistical difference among them.The mean MU values of RapidArc and IMRT were 550 and 1,379.The mean treatment time of RapidArc and IMRT was 165 s and 447 s.Compared to IMRT,the delivery time and the MU values of RapidArc were reduced by 63% and 60%,respectively.Conclusion:For locally advanced NPC,both RapidArc and IMRT reached

  7. Conformational dynamics of a ligand-free adenylate kinase.

    Directory of Open Access Journals (Sweden)

    Hyun Deok Song

    Full Text Available Adenylate kinase (AdK is a phosphoryl-transfer enzyme with important physiological functions. Based on a ligand-free open structure and a ligand-bound closed structure solved by crystallography, here we use molecular dynamics simulations to examine the stability and dynamics of AdK conformations in the absence of ligands. We first perform multiple simulations starting from the open or the closed structure, and observe their free evolutions during a simulation time of 100 or 200 nanoseconds. In all seven simulations starting from the open structure, AdK remained stable near the initial conformation. The eight simulations initiated from the closed structure, in contrast, exhibited large variation in the subsequent evolutions, with most (seven undergoing large-scale spontaneous conformational changes and approaching or reaching the open state. To characterize the thermodynamics of the transition, we propose and apply a new sampling method that employs a series of restrained simulations to calculate a one-dimensional free energy along a curved pathway in the high-dimensional conformational space. Our calculated free energy profile features a single minimum at the open conformation, and indicates that the closed state, with a high (∼13 kcal/mol free energy, is not metastable, consistent with the observed behaviors of the unrestrained simulations. Collectively, our simulations suggest that it is energetically unfavorable for the ligand-free AdK to access the closed conformation, and imply that ligand binding may precede the closure of the enzyme.

  8. Dynamics and zeta functions on conformally compact manifolds

    CERN Document Server

    Rowlett, Julie; Tapie, Samuel

    2011-01-01

    In this note, we study the dynamics and associated zeta functions of conformally compact manifolds with variable negative sectional curvatures. We begin with a discussion of a larger class of manifolds known as convex co-compact manifolds with variable negative curvature. Applying results from dynamics on these spaces, we obtain optimal meromorphic extensions of weighted dynamical zeta functions and asymptotic counting estimates for the number of weighted closed geodesics. A meromorphic extension of the standard dynamical zeta function and the prime orbit theorem follow as corollaries. Finally, we investigate interactions between the dynamics and spectral theory of these spaces.

  9. The conformational dynamics of the mitochondrial Hsp70 chaperone.

    Science.gov (United States)

    Mapa, Koyeli; Sikor, Martin; Kudryavtsev, Volodymyr; Waegemann, Karin; Kalinin, Stanislav; Seidel, Claus A M; Neupert, Walter; Lamb, Don C; Mokranjac, Dejana

    2010-04-09

    Heat shock proteins 70 (Hsp70) represent a ubiquitous and conserved family of molecular chaperones involved in a plethora of cellular processes. The dynamics of their ATP hydrolysis-driven and cochaperone-regulated conformational cycle are poorly understood. We used fluorescence spectroscopy to analyze, in real time and at single-molecule resolution, the effects of nucleotides and cochaperones on the conformation of Ssc1, a mitochondrial member of the family. We report that the conformation of its ADP state is unexpectedly heterogeneous, in contrast to a uniform ATP state. Substrates are actively involved in determining the conformation of Ssc1. The J protein Mdj1 does not interact transiently with the chaperone, as generally believed, but rather is released slowly upon ATP hydrolysis. Analysis of the major bacterial Hsp70 revealed important differences between highly homologous members of the family, possibly explaining tuning of Hsp70 chaperones to meet specific functions in different organisms and cellular compartments.

  10. Strong dynamics, composite Higgs and the conformal window

    CERN Document Server

    Nogradi, Daniel

    2016-01-01

    We review recent progress in the lattice investigations of near-conformal non-abelian gauge theories relevant for dynamical symmetry breaking and model building of composite Higgs models. The emphasis is placed on the mass spectrum and the running renormalized coupling. The role of a light composite scalar isosinglet particle as a composite Higgs particle is highlighted.

  11. Thermal adaptation of conformational dynamics in ribonuclease H.

    Directory of Open Access Journals (Sweden)

    Kate A Stafford

    Full Text Available The relationship between inherent internal conformational processes and enzymatic activity or thermodynamic stability of proteins has proven difficult to characterize. The study of homologous proteins with differing thermostabilities offers an especially useful approach for understanding the functional aspects of conformational dynamics. In particular, ribonuclease HI (RNase H, an 18 kD globular protein that hydrolyzes the RNA strand of RNA:DNA hybrid substrates, has been extensively studied by NMR spectroscopy to characterize the differences in dynamics between homologs from the mesophilic organism E. coli and the thermophilic organism T. thermophilus. Herein, molecular dynamics simulations are reported for five homologous RNase H proteins of varying thermostabilities and enzymatic activities from organisms of markedly different preferred growth temperatures. For the E. coli and T. thermophilus proteins, strong agreement is obtained between simulated and experimental values for NMR order parameters and for dynamically averaged chemical shifts, suggesting that these simulations can be a productive platform for predicting the effects of individual amino acid residues on dynamic behavior. Analyses of the simulations reveal that a single residue differentiates between two different and otherwise conserved dynamic processes in a region of the protein known to form part of the substrate-binding interface. Additional key residues within these two categories are identified through the temperature-dependence of these conformational processes.

  12. Dynamics of particles around time conformal Schwarzschild black hole

    Energy Technology Data Exchange (ETDEWEB)

    Jawad, Abdul; Shahzad, M.U. [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan); Ali, Farhad [Kohat University of Science and Technology, Department of Mathematics, Kohat (Pakistan); Abbas, G. [The Islamia University of Bahawalpur, Department of Mathematics, Bahawalpur (Pakistan)

    2016-11-15

    In this work, we present the new technique for discussing the dynamical motion of neutral as well as charged particles in the absence/presence of a magnetic field around the time conformal Schwarzschild black hole. Initially, we find the numerical solutions of geodesics of the Schwarzschild black hole and the time conformal Schwarzschild black hole. We observe that the Schwarzschild spacetime admits the time conformal factor e{sup εf(t)}, where f(t) is an arbitrary function and ε is very small, which causes a perturbation in the spacetimes. This technique also re-scales the energy content of spacetime. We also investigate the thermal stability, horizons and energy conditions corresponding to time conformal Schwarzschild spacetime. Also, we examine the dynamics of a neutral and charged particle around a time conformal Schwarzschild black hole. We investigate the circumstances under which the particle can escape from the vicinity of a black hole after collision with another particle. We analyze the effective potential and effective force of a particle in the presence of a magnetic field with angular momentum graphically. (orig.)

  13. Estimation of dynamic properties of attractors observed in hollow copper electrode atmospheric pressure arc plasma system

    Indian Academy of Sciences (India)

    S Ghorul; S N Sahasrabudhe; P S S Murthy; A K Das; N Venkatramani

    2002-07-01

    Understanding of the basic nature of arc root fluctuation is still one of the unsolved problems in thermal arc plasma physics. It has direct impact on myriads of thermal plasma applications being implemented at present. Recently, chaotic nature of arc root behavior has been reported through the analysis of voltages, acoustic and optical signals which are generated from a hollow copper electrode arc plasma torch. In this paper we present details of computations involved in the estimation process of various dynamic properties and show how they reflect chaotic behavior of arc root in the system.

  14. Dynamic character analysis for the arc welding power source based on fuzzy logic

    Institute of Scientific and Technical Information of China (English)

    Wang Zhenmin; Xue Jiaxiang; Wang Fuguang

    2007-01-01

    A lot of experimental methods have been brought forth to assess the dynamic character of the arc welding power source, but up to now, this issue has not been solved very well. In this paper, based on the fuzzy logic reasoning method, a dynamic character assessing model for the arc welding power source was established and used to analyze the dynamic character of the welding power source. Three different types of welding machine have been tested, and the characteristic information of the electrical signals such as re-striking arc voltage, low welding current and so on of the welding process were extracted accurately by using a self-developed welding dynamic arc wavelet analyzer. The experimental results indicate that this model can be used as a new assessing method for the dynamic character of the arc welding power source.

  15. Dynamics of diachronous back-arc extension: insights from 3D thermo-mechanical analogue experiments

    Science.gov (United States)

    Boutelier, D. A.; Cruden, A. R.

    2013-12-01

    Subduction of an old, dense oceanic lithosphere can lead to rifting and extension of the magmatic arc. Such subduction systems are inherently three-dimensional with significant along-strike variations in the timing and style of deformation and magmatism. Geodynamic models used to explain such variations and associated trench curvature generally ignore the role of the overriding plate and its deformation. 3D thermo-mechanical analogue experiments are used to investigate the kinematics and dynamics of diachronous arc rifting and back-arc basin opening. In the models, horizontal tension increases in the upper plate until the magmatic arc lithosphere fails and back-arc opening occurs via slab rollback. This result corresponds well to previous 2D models of arc rifting and subsequent back-arc opening via trench rollback and the mechanics of retreating slabs in fluid dynamic experiments. However, in our experiments arc failure occurs diachronously, initiating near the model edge due to locally higher temperatures and lower strength and then propagating along strike, producing an arcuate plate boundary. The experiments demonstrate that trench rollback rate is limited by the propagation rate of arc failure. Conversely, slab rollback generates additional horizontal tension in the adjacent magmatic arc lithosphere, which drives along-strike propagation of arc failure. Feedback between the rates of trench rollback and arc failure propagation dictates the geometry of the back-arc basin in plan-view. The shape of the back-arc basin obtained in models fits remarkably well with that of the Mariana basin in the western Pacific. Experiments where the strength of the magmatic arc, or forearc varies along strike or where the negative buoyancy of the subducting plate varies along strike explore further the role of the slab edge and the trench-parallel tensile strength of the retreating forearc block.

  16. Conformations of terminal sialyloligosaccharide fragments--a molecular dynamics study.

    Science.gov (United States)

    Suresh, M Xavier; Veluraja, K

    2003-06-07

    Molecular dynamics simulations have been performed to understand the conformational features of the terminal sialyloligosaccharide fragments NeuNAc alpha(2-3)Gal, NeuNAc alpha(2-6)Gal, NeuNAc alpha(2-8)NeuNAc and NeuNAc alpha(2-9)NeuNAc. The conformational regions A(i), B(i) and C(i) were identified in the Ramachandran plot. Analysis of the 1000 ps trajectories collected through simulation (2000 ps in the case of NeuNAc alpha (2-9)NeuNAc) revealed that these molecules have conformational propensity in region B(i). The occurrence of these molecules in the common conformational space leads to a structural similarity between them. This structural similarity may be an essential requirement for the neuraminidase activity towards sialyloligosaccharides. The local change in the conformation of the active site residues of neuraminidases may contribute for the specificity differences between different linkages of sialyloligosaccharides. A highly conserved water-mediated hydrogen bond observed in these structures between the sugar residues, acts as an additional stabilizing force.

  17. Solution conformation and dynamics of exopolysaccharides from Burkholderia species.

    Science.gov (United States)

    Pol-Fachin, Laercio; Serrato, Rodrigo V; Verli, Hugo

    2010-09-03

    Exopolysaccharides (EPSs) from the Burkholderia genus are proposed to be involved in pathological conditions in humans, such as cystic fibrosis and septicemia, as well as in the stability of soil aggregates. Hence, considering that the conformational and dynamic aspects of such EPSs may influence their biological activity, the current work employs a series of molecular dynamics simulations on di-, oligo-, and polysaccharide fragments of three EPSs, from Burkholderia caribensis, Burkholderia cepacia, and Burkholderia pseudomallei, with previously determined NOE data, to obtain a conformational description of such EPSs at the atomic level. As the obtained results show good agreement with the experimental data, pointing to the adequacy of the employed methodology to accurately describe the dynamics of polysaccharides, the strategy was also employed to predict the conformational behavior of an additional compound, from Burkholderia tropica, for which NOE signals are not available. Taking into account the potential importance of EPSs on the interaction of Burkholderia bacteria with distinct environments, it may be expected that a greater understanding of their structural aspects may contribute to controlling their pathological roles and potential agricultural applications.

  18. SU-E-T-562: Motion Tracking Optimization for Conformal Arc Radiotherapy Plans: A QUASAR Phantom Based Study

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Z; Wang, I; Yao, R; Podgorsak, M [Roswell Park Cancer Institute, Buffalo, NY (United States)

    2015-06-15

    Purpose: This study is to use plan parameters optimization (Dose rate, collimator angle, couch angle, initial starting phase) to improve the performance of conformal arc radiotherapy plans with motion tracking by increasing the plan performance score (PPS). Methods: Two types of 3D conformal arc plans were created based on QUASAR respiratory motion phantom with spherical and cylindrical targets. Sinusoidal model was applied to the MLC leaves to generate motion tracking plans. A MATLAB program was developed to calculate PPS of each plan (ranges from 0–1) and optimize plan parameters. We first selected the dose rate for motion tracking plans and then used simulated annealing algorithm to search for the combination of the other parameters that resulted in the plan of the maximal PPS. The optimized motion tracking plan was delivered by Varian Truebeam Linac. In-room cameras and stopwatch were used for starting phase selection and synchronization between phantom motion and plan delivery. Gaf-EBT2 dosimetry films were used to measure the dose delivered to the target in QUASAR phantom. Dose profiles and Truebeam trajectory log files were used for plan delivery performance evaluation. Results: For spherical target, the maximal PPS (PPSsph) of the optimized plan was 0.79: (Dose rate: 500MU/min, Collimator: 90°, Couch: +10°, starting phase: 0.83π). For cylindrical target, the maximal PPScyl was 0.75 (Dose rate: 300MU/min, Collimator: 87°, starting phase: 0.97π) with couch at 0°. Differences of dose profiles between motion tracking plans (with the maximal and the minimal PPS) and 3D conformal plans were as follows: PPSsph=0.79: %ΔFWHM: 8.9%, %Dmax: 3.1%; PPSsph=0.52: %ΔFWHM: 10.4%, %Dmax: 6.1%. PPScyl=0.75: %ΔFWHM: 4.7%, %Dmax: 3.6%; PPScyl=0.42: %ΔFWHM: 12.5%, %Dmax: 9.6%. Conclusion: By achieving high plan performance score through parameters optimization, we can improve target dose conformity of motion tracking plan by decreasing total MLC leaf travel distance

  19. Structure and conformational dynamics of scaffolded DNA origami nanoparticles.

    Science.gov (United States)

    Pan, Keyao; Bricker, William P; Ratanalert, Sakul; Bathe, Mark

    2017-06-20

    Synthetic DNA is a highly programmable nanoscale material that can be designed to self-assemble into 3D structures that are fully determined by underlying Watson-Crick base pairing. The double crossover (DX) design motif has demonstrated versatility in synthesizing arbitrary DNA nanoparticles on the 5-100 nm scale for diverse applications in biotechnology. Prior computational investigations of these assemblies include all-atom and coarse-grained modeling, but modeling their conformational dynamics remains challenging due to their long relaxation times and associated computational cost. We apply all-atom molecular dynamics and coarse-grained finite element modeling to DX-based nanoparticles to elucidate their fine-scale and global conformational structure and dynamics. We use our coarse-grained model with a set of secondary structural motifs to predict the equilibrium solution structures of 45 DX-based DNA origami nanoparticles including a tetrahedron, octahedron, icosahedron, cuboctahedron and reinforced cube. Coarse-grained models are compared with 3D cryo-electron microscopy density maps for these five DNA nanoparticles and with all-atom molecular dynamics simulations for the tetrahedron and octahedron. Our results elucidate non-intuitive atomic-level structural details of DX-based DNA nanoparticles, and offer a general framework for efficient computational prediction of global and local structural and mechanical properties of DX-based assemblies that are inaccessible to all-atom based models alone. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Conformation and intramolecular relaxation dynamics of semiflexible randomly hyperbranched polymers

    Science.gov (United States)

    Kumar, Amit; Rai, Gobind Ji; Biswas, Parbati

    2013-03-01

    The conformational and dynamic properties of semiflexible randomly hyperbranched polymers are investigated in dilute solutions within the framework of optimized Rouse-Zimm formalism. Semiflexibility is incorporated by restricting the directions and orientations of the respective bond vectors, while hydrodynamic interactions are modeled through the preaveraged Oseen tensor. The effect of semiflexibility is typically reflected in the intermediate frequency regime of the viscoelastic relaxation moduli where the bond orientation angle restores the characteristic power-law scaling in fractal structures, as in randomly hyperbranched polymers. Despite the absence of this power-law scaling regime in flexible randomly hyperbranched polymers and in earlier models of semiflexible randomly branched polymers due to weak disorder [C. von Ferber and A. Blumen, J. Chem. Phys. 116, 8616 (2002)], 10.1063/1.1470198, this power-law behavior may be reinstated by explicitly modeling hyperbranched polymers as a Vicsek fractals. The length of this power-law zone in the intermediate frequency region is a combined function of the number of monomers and the degree of semiflexibility. A clear conformational transition from compact to open structures is facilitated by changing the bond orientation angle, where the compressed conformations are compact, while the expanded ones are relatively non-compact. The extent of compactness in the compressed conformations are much less compared to the semiflexible dendrimers, which resemble hard spheres. The fractal dimensions of the compressed and expanded conformations calculated from the Porod's scaling law vary as a function of the bond orientation angle, spanning the entire range of three distinct scaling regimes of linear polymers in three-dimensions. The results confirm that semiflexibility exactly accounts for the excluded volume interactions which are expected to be significant for such polymers with complex topologies.

  1. Influence of conformational molecular dynamics on matter wave interferometry

    CERN Document Server

    Gring, Michael; Eibenberger, Sandra; Nimmrichter, Stefan; Berrada, Tarik; Arndt, Markus; Ulbricht, Hendrik; Hornberger, Klaus; Müri, Marcel; Mayor, Marcel; Böckmann, Marcus; Doltsinis, Nikos

    2014-01-01

    We investigate the influence of thermally activated internal molecular dynamics on the phase shifts of matter waves inside a molecule interferometer. While de Broglie physics generally describes only the center-of-mass motion of a quantum object, our experiment demonstrates that the translational quantum phase is sensitive to dynamic conformational state changes inside the diffracted molecules. The structural flexibility of tailor-made hot organic particles is sufficient to admit a mixture of strongly fluctuating dipole moments. These modify the electric susceptibility and through this the quantum interference pattern in the presence of an external electric field. Detailed molecular dynamics simulations combined with density functional theory allow us to quantify the time-dependent structural reconfigurations and to predict the ensemble-averaged square of the dipole moment which is found to be in good agreement with the interferometric result. The experiment thus opens a new perspective on matter wave interfe...

  2. Computational study of flow dynamics from a dc arc plasma jet

    CERN Document Server

    Trelles, Juan Pablo

    2013-01-01

    Plasma jets produced by direct-current (DC) non-transferred arc plasma torches, at the core of technologies ranging from spray coating to pyrolysis, present intricate dynamics due to the coupled interaction of fluid flow, thermal, and electromagnetic phenomena. The flow dynamics from an arc discharge plasma jet are investigated using time-dependent three-dimensional simulations encompassing the dynamics of the arc inside the torch, the evolution of the jet through the discharge environment, and the subsequent impingement of the jet over a flat substrate. The plasma is described by a chemical equilibrium and thermodynamic nonequilibrium (two-temperature) model. The numerical formulation of the physical model is based on a monolithic and fully-coupled treatment of the fluid and electromagnetic equations using a Variational Multiscale Finite Element Method. Simulation results uncover distinct aspects of the flow dynamics, including the jet forcing due to the movement of the electric arc, the prevalence of deviat...

  3. A Conformal Truncation Framework for Infinite-Volume Dynamics

    CERN Document Server

    Katz, Emanuel; Walters, Matthew T

    2016-01-01

    We present a new framework for studying conformal field theories deformed by one or more relevant operators. The original CFT is described in infinite volume using a basis of states with definite momentum, $P$, and conformal Casimir, $\\mathcal{C}$. The relevant deformation is then considered using lightcone quantization, with the resulting Hamiltonian expressed in terms of this CFT basis. Truncating to states with $\\mathcal{C} \\leq \\mathcal{C}_{\\max}$, one can numerically find the resulting spectrum, as well as other dynamical quantities, such as spectral densities of operators. This method requires the introduction of an appropriate regulator, which can be chosen to preserve the conformal structure of the basis. We check this framework in three dimensions for various perturbative deformations of a free scalar CFT, and for the case of a free $O(N)$ CFT deformed by a mass term and a non-perturbative quartic interaction at large-$N$. In all cases, the truncation scheme correctly reproduces known analytic result...

  4. Trajectory optimization for dynamic couch rotation during volumetric modulated arc radiotherapy

    Science.gov (United States)

    Smyth, Gregory; Bamber, Jeffrey C.; Evans, Philip M.; Bedford, James L.

    2013-11-01

    Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra’s algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

  5. Time-resolved infrared studies of protein conformational dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Woodruff, W.H.; Causgrove, T.P.; Dyer, R.B. [Los Alamos National Laboratory, NM (United States); Callender, R.H. [Univ. of New York, NY (United States)

    1994-12-01

    We have demonstrated that TRIR in the amide I region gives structural information regarding protein conformational changes in realtime, both on processes involved in the development of the functional structure (protein folding) and on protein structural changes that accompany the functional dynamics of the native structure. Assignment of many of the amide I peaks to specific amide or sidechain structures will require much additional effort. Specifically, the congestion and complexity of the protein vibrational spectra dictate that isotope studies are an absolute requirement for more than a qualitative notion of the structural interpretation of these measurements. It is clear, however, that enormous potential exists for elucidating structural relaxation dynamics and energetics with a high degree of structural specificity using this approach.

  6. Probabilistic modelling of the high-pressure arc cathode spot displacement dynamic

    CERN Document Server

    Coulombe, S

    2003-01-01

    A probabilistic modelling approach for the study of the cathode spot displacement dynamic in high-pressure arc systems is developed in an attempt to interpret the observed voltage fluctuations. The general framework of the model allows to define simple, probabilistic displacement rules, the so-called cathode spot dynamic rules, for various possible surface states (un-arced metal, arced, contaminated) and to study the resulting dynamic of the cathode spot displacements over one or several arc passages. The displacements of the type-A cathode spot (macro-spot) in a magnetically rotating arc using concentric electrodes made up of either clean or contaminated metal surfaces is considered. Experimental observations for this system revealed a 1/f sup - sup t sup i sup l sup d sup e sup 1 signature in the frequency power spectrum (FPS) of the arc voltage for anchoring arc conditions on the cathode (e.g. clean metal surface), while it shows a 'white noise' signature for conditions favouring a smooth movement (e.g. ox...

  7. TU-CD-304-03: Dosimetric Verification and Preliminary Comparison of Dynamic Wave Arc for SBRT Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Burghelea, M [UZ BRUSSEL, Brussels (Belgium); BRAINLAB AG, Munich (Germany); Babes Bolyai University, Cluj-Napoca (Romania); Poels, K; Gevaert, T; Tournel, K; Dhont, J; De Ridder, M; Verellen, D [UZ BRUSSEL, Brussels (Belgium); Hung, C [BRAINLAB AG, Munich (Germany); Eriksson, K [RAYSEARCH LABORATORIES AB, Stockholm (Sweden); Simon, V [Babes Bolyai University, Cluj-Napoca (Romania)

    2015-06-15

    Purpose: To evaluate the potential dosimetric benefits and verify the delivery accuracy of Dynamic Wave Arc, a novel treatment delivery approach for the Vero SBRT system. Methods: Dynamic Wave Arc (DWA) combines simultaneous movement of gantry/ring with inverse planning optimization, resulting in an uninterrupted non-coplanar arc delivery technique. Thirteen SBRT complex cases previously treated with 8–10 conformal static beams (CRT) were evaluated in this study. Eight primary centrally-located NSCLC (prescription dose 4×12Gy or 8×7.5Gy) and five oligometastatic cases (2×2 lesions, 10×5Gy) were selected. DWA and coplanar VMAT plans, partially with dual arcs, were generated for each patient using identical objective functions for target volumes and OARs on the same TPS (RayStation, RaySearch Laboratories). Dosimetric differences and delivery time among these three planning schemes were evaluated. The DWA delivery accuracy was assessed using the Delta4 diode array phantom (ScandiDos AB). The gamma analysis was performed with the 3%/3mm dose and distance-to-agreement criteria. Results: The target conformity for CRT, VMAT and DWA were 0.95±0.07, 0.96±0.04 and 0.97±0.04, while the low dose spillage gradient were 5.52±1.36, 5.44±1.11, and 5.09±0.98 respectively. Overall, the bronchus, esophagus and spinal cord maximum doses were similar between VMAT and DWA, but highly reduced compared with CRT. For the lung cases, the mean dose and V20Gy were lower for the arc techniques compares with CRT, while for the liver cases, the mean dose and the V30Gy presented slightly higher values. The average delivery time of VMAT and DWA were 2.46±1.10 min and 4.25±1.67 min, VMAT presenting shorter treatment time in all cases. The DWA dosimetric verification presented an average gamma index passing rate of 95.73±1.54% (range 94.2%–99.8%). Conclusion: Our preliminary data indicated that the DWA is deliverable with clinically acceptable accuracy and has the potential to

  8. A dosimetric comparison of 3D conformal vs intensity modulated vs volumetric arc radiation therapy for muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Foroudi Farshad

    2012-07-01

    Full Text Available Abstract Background To compare 3 Dimensional Conformal radiotherapy (3D-CRT with Intensity Modulated Radiotherapy (IMRT with Volumetric-Modulated Arc Therapy (VMAT for bladder cancer. Methods Radiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated. Results Mean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250–293 for 3D-CRT; 824 (range 641–1083 for IMRT; and 403 (range 333–489 for VMAT (P  Conclusions VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours.

  9. Conformal dynamics of fractal growth patterns without randomness

    Science.gov (United States)

    Davidovitch; Feigenbaum; Hentschel; Procaccia

    2000-08-01

    Many models of fractal growth patterns (such as diffusion limited aggregation and dielectric breakdown models) combine complex geometry with randomness; this double difficulty is a stumbling block to their elucidation. In this paper we introduce a wide class of fractal growth models with highly complex geometry but without any randomness in their growth rules. The models are defined in terms of deterministic itineraries of iterated conformal maps, generating the function Phi((n))(omega) which maps the exterior of the unit circle to the exterior of an n-particle growing aggregate. The complexity of the evolving interfaces is fully contained in the deterministic dynamics of the conformal map Phi((n))(omega). We focus attention on a class of growth models in which the itinerary is quasiperiodic. Such itineraries can be approached via a series of rational approximants. The analytic power gained is used to introduce a scaling theory of the fractal growth patterns and to identify the exponent that determines the fractal dimension.

  10. Enhanced molecular dynamics sampling of drug target conformations.

    Science.gov (United States)

    Rodriguez-Bussey, Isela G; Doshi, Urmi; Hamelberg, Donald

    2016-01-01

    Computational docking and virtual screening are two main important methods employed in structure-based drug design. Unlike the traditional approach that allows docking of a flexible ligand against a handful of receptor structures, receptor flexibility has now been appreciated and increasingly incorporated in computer-aided docking. Using a diverse set of receptor conformations increases the chances of finding potential drugs and inhibitors. Molecular dynamics (MD) is greatly useful to generate various receptor conformations. However, the diversity of the structures of the receptor, which is usually much larger than the ligand, depends on the sampling efficiency of MD. Enhanced sampling methods based on accelerated molecular dynamics (aMD) can alleviate the sampling limitation of conventional MD and aid in representation of the phase space to a much greater extent. RaMD-db, a variant of aMD that applies boost potential to the rotatable dihedrals and non-bonded diffusive degrees of freedom has been proven to reproduce the equilibrium properties more accurately and efficiently than aMD. Here, we discuss recent advances in the aMD methodology and review the applicability of RaMD-db as an enhanced sampling method. RaMD-db is shown to be able to generate a broad distribution of structures of a drug target, Cyclophilin A. These structures that have never been observed previously in very long conventional MD can be further used for structure-based computer-aided drug discovery, and docking, and thus, in the identification and design of potential novel inhibitors.

  11. Molecular dynamics simulation study on zwitterionic structure to maintain the normal conformations of Glutathione

    Institute of Scientific and Technical Information of China (English)

    YAN; Han; ZHU; HaoMiao; SHEN; Jian

    2007-01-01

    Molecular dynamics simulations were applied to normal conformational Glutathione (GSH) and GSH over zwitterionic and hydrophobic surfaces respectively. Conformational analysis of GSH during the simulation time on RMSD, conformational flexibility and dihedral distribution were performed. The results showed that zwitterionic structure maintains the normal conformations of GSH to a better extent, which should be a first good proof of the hypothesis of "maintain of normal structure".

  12. Binary cluster collision dynamics and minimum energy conformations

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Francisco [Max Planck Institute of Microstructure Physics, Weinberg 2, 06120 Halle (Germany); Departamento de Física, Facultad de Ciencias, Universidad de Chile, Santiago (Chile); Centro para el Desarrollo de la Nanociencia y Nanotecnología, CEDENNA, Avenida Ecuador 3493, Santiago (Chile); Rogan, José; Valdivia, J.A. [Departamento de Física, Facultad de Ciencias, Universidad de Chile, Santiago (Chile); Centro para el Desarrollo de la Nanociencia y Nanotecnología, CEDENNA, Avenida Ecuador 3493, Santiago (Chile); Varas, A. [Departamento de Física, Facultad de Ciencias, Universidad de Chile, Santiago (Chile); Nano-Bio Spectroscopy Group, ETSF Scientific Development Centre, Departamento de Física de Materiales, Universidad del País Vasco UPV/EHU, Av. Tolosa 72, E-20018 San Sebastián (Spain); Kiwi, Miguel, E-mail: m.kiwi.t@gmail.com [Departamento de Física, Facultad de Ciencias, Universidad de Chile, Santiago (Chile); Centro para el Desarrollo de la Nanociencia y Nanotecnología, CEDENNA, Avenida Ecuador 3493, Santiago (Chile)

    2013-10-15

    The collision dynamics of one Ag or Cu atom impinging on a Au{sub 12} cluster is investigated by means of DFT molecular dynamics. Our results show that the experimentally confirmed 2D to 3D transition of Au{sub 12}→Au{sub 13} is mostly preserved by the resulting planar Au{sub 12}Ag and Au{sub 12}Cu minimum energy clusters, which is quite remarkable in view of the excess energy, well larger than the 2D–3D potential barrier height. The process is accompanied by a large s−d hybridization and charge transfer from Au to Ag or Cu. The dynamics of the collision process mainly yields fusion of projectile and target, however scattering and cluster fragmentation also occur for large energies and large impact parameters. While Ag projectiles favor fragmentation, Cu favors scattering due to its smaller mass. The projectile size does not play a major role in favoring the fragmentation or scattering channels. By comparing our collision results with those obtained by an unbiased minimum energy search of 4483 Au{sub 12}Ag and 4483 Au{sub 12}Cu configurations obtained phenomenologically, we find that there is an extra bonus: without increase of computer time collisions yield the planar lower energy structures that are not feasible to obtain using semi-classical potentials. In fact, we conclude that phenomenological potentials do not even provide adequate seeds for the search of global energy minima for planar structures. Since the fabrication of nanoclusters is mainly achieved by synthesis or laser ablation, the set of local minima configurations we provide here, and their distribution as a function of energy, are more relevant than the global minimum to analyze experimental results obtained at finite temperatures, and is consistent with the dynamical coexistence of 2D and 3D liquid Au clusters conformations obtained previously.

  13. Dynamics of cathode spots in low-pressure arc plasma removing oxide layer on steel surfaces

    Science.gov (United States)

    Tang, Z. L.; Yang, K.; Liu, H. X.; Zhang, Y. C.; Li, H.; Zhu, X. D.

    2016-03-01

    The dynamics of cathode spots has been investigated in low-pressure arc plasma for removing oxide layer on low carbon steel surfaces. The motion of cathode spots was observed with a high speed camera, and the arc voltage was analyzed by fast Fourier transform. The spots move on clean steel surface as a random walk, and the low-frequency components dominated the voltage waveform. However, the spots on steel surfaces with oxide layer tend to burn on the rim of the eroded area formed in the previous arcing, and the low-frequency components decrease correspondingly. The "color" of the colored random noise for arc voltage varies from the approximate brown noise for clean steel surface to pink noise for thick oxide layer, where the edge effect of boundary is considered to play a significant role.

  14. Plasma Processes : Arc root dynamics in high power plasma torches – Evidence of chaotic behavior

    Indian Academy of Sciences (India)

    A K Das

    2000-11-01

    Although plasma torches have been commercially available for about 50 years, areas such as plasma gun design, process efficiency, reproducibility, plasma stability, torch lives etc. have remained mostly unattended. Recent torch developments have been focusing on the basic understanding of the plasma column and its dynamics inside the plasma torch, the interaction of plasma jet and the powders, the interaction of the plasma jet with surroundings and the impingement of the jet on the substrate. Two of the major causes of erratic and poor performance of a variety of thermal plasma processes are currently identified as the fluctuations arising out of the arc root movement on the electrodes inside the plasma torch and the fluid dynamic instabilities arising out of entrainment of the air into the plasma jet. This paper reviews the current state of understanding of these fluctuations as well as the dynamics of arc root movement in plasma torches. The work done at the author’s laboratory on studying the fluctuations in arc voltage, arc current, acoustic emissions and optical emissions are also presented. These fluctuations are observed to be chaotic and interrelated. Real time monitoring and controlling the arc instabilities through chaos characterization parameters can greatly contribute to the understanding of electrode erosion as well as improvement of plasma torch lifetime.

  15. Multiple Conformations of E. Coli Hsp90 in Solution: Insights Into the Conformational Dynamics of Hsp90

    Energy Technology Data Exchange (ETDEWEB)

    Krukenberg, K.A.; Forster, F.; Rice, L.M.; Sali, A.; Agard, D.A.

    2009-05-20

    Hsp90, an essential eukaryotic chaperone, depends upon its intrinsic ATPase activity for function. Crystal structures of the bacterial Hsp90 homolog, HtpG, and the yeast Hsp90 reveal large domain rearrangements between the nucleotide-free and the nucleotide-bound forms. We used small-angle X-ray scattering and recently developed molecular modeling methods to characterize the solution structure of HtpG and demonstrate how it differs from known Hsp90 conformations. In addition to this HtpG conformation, we demonstrate that under physiologically relevant conditions, multiple conformations coexist in equilibrium. In solution, nucleotide-free HtpG adopts a more extended conformation than observed in the crystal, and upon the addition of AMPPNP, HtpG is in equilibrium between this open state and a closed state that is in good agreement with the yeast AMPPNP crystal structure. These studies provide a unique view of Hsp90 conformational dynamics and provide a model for the role of nucleotide in effecting conformational change.

  16. Dynamic Arc SUMOylation and Selective Interaction with F-Actin-Binding Protein Drebrin A in LTP Consolidation In Vivo

    Science.gov (United States)

    Nair, Rajeevkumar R.; Patil, Sudarshan; Tiron, Adrian; Kanhema, Tambudzai; Panja, Debabrata; Schiro, Lars; Parobczak, Kamil; Wilczynski, Grzegorz; Bramham, Clive R.

    2017-01-01

    Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as a master regulator of long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. Post-translation modification by small ubiquitin-like modifier (SUMO) proteins has emerged as a major mechanism for regulating protein-protein interactions and function. We first show in cell lines that ectopically expressed Arc undergoes mono-SUMOylation. The covalent addition of a single SUMO1 protein was confirmed by in vitro SUMOylation of immunoprecipitated Arc. To explore regulation of endogenous Arc during synaptic plasticity, we induced long-term potentiation (LTP) in the dentate gyrus of live anesthetized rats. Using coimmunoprecipitation of native proteins, we show that Arc synthesized during the maintenance phase of LTP undergoes dynamic mono-SUMO1-ylation. Levels of unmodified Arc increase in multiple subcellular fractions (cytosol, membrane, nuclear and cytoskeletal), whereas enhanced Arc SUMOylation was specific to the synaptoneurosomal and the cytoskeletal fractions. Dentate gyrus LTP consolidation requires a period of sustained Arc synthesis driven by brain-derived neurotrophic factor (BDNF) signaling. Local infusion of the BDNF scavenger, TrkB-Fc, during LTP maintenance resulted in rapid reversion of LTP, inhibition of Arc synthesis and loss of enhanced Arc SUMO1ylation. Furthermore, coimmunoprecipitation analysis showed that SUMO1-ylated Arc forms a complex with the F-actin-binding protein drebrin A, a major regulator of cytoskeletal dynamics in dendritic spines. Although Arc also interacted with dynamin 2, calcium/calmodulindependentprotein kinase II-beta (CaMKIIβ), and postsynaptic density protein-95 (PSD-95), these complexes lacked SUMOylated Arc. The results support a model in which newly synthesized Arc is SUMOylated and targeted for actin cytoskeletal regulation during in vivo LTP. PMID:28553222

  17. Temporal dynamics of Arc gene induction in hippocampus: relationship to context memory formation.

    Science.gov (United States)

    Pevzner, Aleksandr; Miyashita, Teiko; Schiffman, Aaron J; Guzowski, John F

    2012-03-01

    Past studies have proposed a role for the hippocampus in the rapid encoding of context memories. Despite this, there is little data regarding the molecular processes underlying the stable formation of a context representation that occurs in the time window established through such behavioral studies. One task that is useful for investigating the rapid encoding of context is contextual fear conditioning (CFC). Behavioral studies demonstrate that animals require approximately 30 s of exploration prior to a footshock to form a contextual representation supporting CFC. Thus, any potential molecular process required for the stabilization of the cellular representation for context must be activated within this narrow and behaviorally defined time window. Detection of the immediate-early gene Arc presents an ideal method to assess the activation of specific neuronal ensembles, given past studies showing the context specific expression of Arc in CA3 and CA1 subfields and the role of Arc in hippocampal long-term synaptic plasticity. Therefore, we examined the temporal dynamics of Arc induction within the hippocampus after brief context exposure to determine whether experience-dependent Arc expression could be involved in the rapid encoding of incidental context memories. We found that the duration of context exposure differentially activated Arc expression in hippocampal subfields, with CA3 showing rapid engagement within as little as 3 s of exposure. By contrast, Arc induction in CA1 required 30 s of context exposure to reach maximal levels. A parallel behavioral experiment revealed that 30 s, but not 3 s, exposure to a context resulted in strong conditioned freezing 24 h later, consistent with past studies from other laboratories. The current study is the first to examine the rapid temporal dynamics of Arc induction in hippocampus in a well-defined context memory paradigm. These studies demonstrate within 30 s of context exposure Arc is fully activated in CA3 and CA1

  18. Single arc volumetric-modulated arc therapy is sufficient for nasopharyngeal carcinoma: a dosimetric comparison with dual arc VMAT and dynamic MLC and step-and-shoot intensity-modulated radiotherapy

    Science.gov (United States)

    2013-01-01

    Background The performance of single arc VMAT (VMAT1) for nasopharyngeal carcinoma (NPC) on the Axesse linac has not been well described in previous studies. The purpose of this study is to assess the feasibility of VMAT1 for NPC by comparing the dosimetry, delivery efficiency, and accuracy with dual arc VMAT (VMAT2), dynamic MLC intensity-modulated radiotherapy (dIMRT), and step-and-shoot intensity-modulated radiotherapy (ssIMRT). Methods Twenty consecutive patients with non-metastatic NPC were selected to be planned with VMAT1, VMAT2, dIMRT and ssIMRT using Monaco 3.2 TPS on the Axesse™ linear accelerator. Three planning target volumes (PTVs), contoured as high risk, moderate risk and low risk regions, were set to receive median absorbed-dose (D50%) of 72.6 Gy, 63.6 Gy and 54 Gy, respectively. The Homogeneity Index (HI), Conformity Index (CI), Dose Volume Histograms (DVHs), delivery efficiency and accuracy were all evaluated. Results Mean HI of PTV72.6 is better with VMAT1(0.07) and VMAT2(0.07) than dIMRT(0.09) and ssIMRT(0.09). Mean HI of PTV63.6 is better with VMAT1(0.21) and VMAT2(0.21) than dIMRT and ssIMRT. Mean CI of PTV72.6 is also better with VMAT1(0.57) and VMAT2(0.57) than dIMRT(0.49) and ssIMRT(0.5). Mean CI of PTV63.6 is better with VMAT1(0.76) and VMAT2(0.76) than dIMRT(0.73) and ssIMRT(0.73). VMAT had significantly improved homogeneity and conformity compared with IMRT. There was no significant difference between VMAT1 and VMAT2 in PTV coverage. Dose to normal tissues was acceptable for all four plan groups. VMAT1 and VMAT2 showed no significant difference in normal tissue sparring, whereas the mean dose of the parotid gland of dIMRT was significantly reduced compared to VMAT1 and VMAT2. The mean delivery time for VMAT1, VMAT2, dIMRT and ssIMRT was 2.7 min, 3.9 min, 5.7 min and 14.1 min, respectively. VMAT1 reduced the average delivery time by 29.8%, 51.1% and 80.8% compared with VMAT2, dIMRT and ssIMRT, respectively. VMAT and IMRT could all be

  19. Simulation on Dynamic Characteristic of Negative Resistance Arc in Pulsed TIG Welding

    Institute of Scientific and Technical Information of China (English)

    YANG Lijun; HAN Pengbo; DONG Tianshun; ZHANG Jian; XU Licheng

    2007-01-01

    A mathematical model is established on the basis of the physical characteristic of the negative resistance arc when a low current of 0-50 A is applied in pulsed TIG welding. The simulation model converted from the mathematical model is run in MATLAB environment, and the discussion is focused on the way the peak current ranging from 29 A to 50 A and the time constant of arc in the span of 0.003-0.006 s influence the simulating results and the dynamic characteristic. The simulating data are close to that of welding experiments and correspond to the theoretical conclusion.

  20. Active site conformational dynamics in human uridine phosphorylase 1.

    Directory of Open Access Journals (Sweden)

    Tarmo P Roosild

    Full Text Available Uridine phosphorylase (UPP is a central enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate. Human UPP activity has been a focus of cancer research due to its role in activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5-fluorouracil (5-FU and capecitabine. Additionally, specific molecular inhibitors of this enzyme have been found to raise endogenous uridine concentrations, which can produce a cytoprotective effect on normal tissues exposed to these drugs. Here we report the structure of hUPP1 bound to 5-FU at 2.3 A resolution. Analysis of this structure reveals new insights as to the conformational motions the enzyme undergoes in the course of substrate binding and catalysis. The dimeric enzyme is capable of a large hinge motion between its two domains, facilitating ligand exchange and explaining observed cooperativity between the two active sites in binding phosphate-bearing substrates. Further, a loop toward the back end of the uracil binding pocket is shown to flexibly adjust to the varying chemistry of different compounds through an "induced-fit" association mechanism that was not observed in earlier hUPP1 structures. The details surrounding these dynamic aspects of hUPP1 structure and function provide unexplored avenues to develop novel inhibitors of this protein with improved specificity and increased affinity. Given the recent emergence of new roles for uridine as a neuron protective compound in ischemia and degenerative diseases, such as Alzheimer's and Parkinson's, inhibitors of hUPP1 with greater efficacy, which are able to boost cellular uridine levels without adverse side-effects, may have a wide range of therapeutic applications.

  1. Conformal invariance and conserved quantities of dynamical system of relative motion

    Institute of Scientific and Technical Information of China (English)

    Chen Xiang-Wei; Zhao Yong-Hong; Li Yan-Min

    2009-01-01

    This paper discusses in detail the conformal invariance by infinitesimal transformations of a dynamical system of relative motion.The necessary and sufficient conditions of conformal invariance and Lie symmetry are given simulta neously by the action of infinitesimal transformations.Then it obtains the conserved quantities of conformal invariance by the infinitesimal transformations.Finally an example is given to illustrate the application of the results.

  2. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    Full Text Available The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  3. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Science.gov (United States)

    Koldsø, Heidi; Autzen, Henriette Elisabeth; Grouleff, Julie; Schiøtt, Birgit

    2013-01-01

    The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  4. Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Keedy, Daniel A.; Kenner, Lillian R.; Warkentin, Matthew; Woldeyes, Rahel A.; Hopkins, Jesse B.; Thompson, Michael C.; Brewster, Aaron S.; Van Benschoten, Andrew H.; Baxter, Elizabeth L.; Uervirojnangkoorn, Monarin; McPhillips, Scott E.; Song, Jinhu; Alonso-Mori, Roberto; Holton, James M.; Weis, William I.; Brunger, Axel T.; Soltis, S. Michael; Lemke, Henrik; Gonzalez, Ana; Sauter, Nicholas K.; Cohen, Aina E.; van den Bedem, Henry; Thorne, Robert E.; Fraser, James S.

    2015-09-30

    Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for structural biology. Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A (CypA) has been previously linked to its catalytic function, but the extent to which the different conformations of these residues are correlated is unclear. Here we compare the conformational ensembles of CypA by multitemperature synchrotron crystallography and fixed-target X-ray free-electron laser (XFEL) crystallography. The diffraction-before-destruction nature of XFEL experiments provides a radiation-damage-free view of the functionally important alternative conformations of CypA, confirming earlier synchrotron-based results. We monitored the temperature dependences of these alternative conformations with eight synchrotron datasets spanning 100-310 K. Multiconformer models show that many alternative conformations in CypA are populated only at 240 K and above, yet others remain populated or become populated at 180 K and below. These results point to a complex evolution of conformational heterogeneity between 180-–240 K that involves both thermal deactivation and solvent-driven arrest of protein motions in the crystal. The lack of a single shared conformational response to temperature within the dynamic active-site network provides evidence for a conformation shuffling model, in which exchange between rotamer states of a large aromatic ring in the middle of the network shifts the conformational ensemble for the other residues in the network. Together, our multitemperature analyses and XFEL data motivate a new generation of temperature- and time-resolved experiments to structurally characterize the dynamic underpinnings of protein function.

  5. Planning study to compare dynamic and rapid arc techniques for postprostatectomy radiotherapy of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cambria, R.; Cattani, F.; Pansini, F.; Vigorito, S.; Russo, S. [Istituto Europeo di Oncologia, Department of Medical Physics, Milan (Italy); Jereczek-Fossa, B.A.; Orecchia, R. [Istituto Europeo di Oncologia, Department of Radiation Oncology, Milan (Italy); Universita degli Studi di Milano, Milan (Italy); Ciardo, D.; Zerini, D. [Istituto Europeo di Oncologia, Department of Radiation Oncology, Milan (Italy); Cozzi, L. [Oncology Institute of Southern Switzerland, Medical Physics Unit, Bellinzona (Switzerland)

    2014-06-15

    To compare our standard technique for postprostatectomy radiotherapy of prostate cancer, i.e. using two lateral conformal dynamic arcs with volumetric-modulated arc therapy (VMAT) performed with the RapidArc {sup registered} (Varian Medical Systems, Palo Alto, CA, USA). The plans were referred to as DA and RA, respectively. The treatment plans of 44 patients receiving adjuvant/salvage radiotherapy in the first months of 2010 were compared. In all cases, the prescribed total dose was 66-68.2 Gy (2.2 Gy per fraction). Both DA and RA plans were optimized in terms of dose coverage and constraints. Small differences between the techniques were observed for planning target volume (PTV) dose distribution, whereas significant differences in sparing of organs at risk (OARs) were recorded (p < 0.0001). The OAR values (median; 95 % confidence interval, CI) were: rectum: D{sub 30} {sub %} = 60.7 Gy (59.40-62.04 Gy) and 48.2 Gy (46.40-52.72 Gy), D{sub 60} {sub %} = 34.1 Gy (28.50-38.92 Gy) and 27.7 Gy (21.80-31.51 Gy); bladder: D{sub 30} {sub %} = 57.3 Gy (45.83-64.53 Gy) and 46.4 Gy (33.23-61.48 Gy), D{sub 50} {sub %} = 16.4 Gy (11.89-42.38 Gy) and 17.2 Gy (10.97-27.90 Gy), for DA and RA, respectively. Treatment times were very similar, whereas the monitor units (MU) were 550 ± 29 versus 277 ± 3 for RA and DA, respectively. Dose-volume histograms (DVHs) show improvements in OAR sparing with RA. However, the RA technique is associated with almost double the number of MUs compared to DA. Regarding the PTV, DA is slightly superior in terms of D{sub 2} {sub %} and dose homogeneity. On the whole, the results suggest that RA be the favorable technique. (orig.) [German] Vergleich unserer Standardtechnik bei der Strahlentherapie nach Prostatektomie bei Prostatakrebs, ausgefuehrt mit zwei lateral dynamischen Rotationsbestrahlungen, der volumenmodulierten Arc-Therapie (VMAT, DA) und der RapidArc {sup registered} (RA, Varian Medical Systems, Palo Alto, CA, USA). Es wurden die

  6. An analysis of the dynamic resistance and the instantaneous energy of the CO2 arc welding process

    Institute of Scientific and Technical Information of China (English)

    Wang Zhenmin; Xue Jiaxiang; Dong Fei; Yang Guohua; Lu Xiaoming

    2007-01-01

    A self-developed welding dynamic arc wavelet analyzer was adopted to analyze and assess the welding process of two CO2 arc welding machines. The experimental results indicate that the instantaneous energy can reflect the influence of the welding current and voltage on dynamic arc characteristic synthetically. Through calculating and analyzing the instantaneous energy, the energy during arc ignition and short circuit in CO2 welding process can be confirmed rationally, thus the foundation for the accurate design and control of the welding current and voltage can be provided. By reducing the ripple disturbance of the dynamic resistance, avoiding peak current and voltage waveform,and enhancing the transition frequency of short circuit suitably, the stability of the welding arc and the weld appearance can be improved.

  7. A comparison of liver protection among 3-D conformal radiotherapy, intensity-modulated radiotherapy and RapidArc for hepatocellular carcinoma

    Science.gov (United States)

    2014-01-01

    Purpose The analysis was designed to compare dosimetric parameters among 3-D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and RapidArc (RA) to identify which can achieve the lowest risk of radiation-induced liver disease (RILD) for hepatocellular carcinoma (HCC). Methods Twenty patients with HCC were enrolled in this study. Dosimetric values for 3DCRT, IMRT, and RA were calculated for total dose of 50 Gy/25f. The percentage of the normal liver volume receiving >40, >30, >20, >10, and >5 Gy (V40, V30, V20, V10 and V5) were evaluated to determine liver toxicity. V5, V10, V20, V30 and Dmean of liver were compared as predicting parameters for RILD. Other parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V110%) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (Dmean) for the organs at risk (OARs) and the maximal dose at 1% volume (D1%) for the spinal cord. Results The Dmean of IMRT was higher than 3DCRT (p = 0.045). For V5, there was a significant difference: RA > IMRT >3DCRT (p delivery time than 3DCRT or IMRT (p 8 cm in our study, the value of Dmean for 3DCRT was lower than IMRT or RapidArc. This may indicate that 3DCRT is more suitable for larger tumors. PMID:24502643

  8. Conformational flexibility of β-secretase:molecular dynamics simulation and essential dynamics analysis

    Institute of Scientific and Technical Information of China (English)

    Bing XIONG; Xiao-qin HUANG; Ling-ling SHEN; Jian-hua SHEN; Xiao-min LUO; Xu SHEN; Hua-liang JIANG; Kai-xian CHEN

    2004-01-01

    AIM: Based on the structural analysis to reveal the mechanism of ligand binding to β-secretase and the specificity of each binding sub-site. METHODS: Molecular dynamics was used to simulate on the ligand free β-secretase and ligand bound β-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly showed that the β-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, Pl, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION: The information presented here is valuable and could be used to identify small molecular inhibitors of β-secretase.

  9. Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

    KAUST Repository

    Feng, Yitao

    2016-10-13

    The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

  10. Structural dynamics associated with intermediate formation in an archetypal conformational disease.

    Science.gov (United States)

    Nyon, Mun Peak; Segu, Lakshmi; Cabrita, Lisa D; Lévy, Géraldine R; Kirkpatrick, John; Roussel, Benoit D; Patschull, Anathe O M; Barrett, Tracey E; Ekeowa, Ugo I; Kerr, Richard; Waudby, Christopher A; Kalsheker, Noor; Hill, Marian; Thalassinos, Konstantinos; Lomas, David A; Christodoulou, John; Gooptu, Bibek

    2012-03-07

    In conformational diseases, native protein conformers convert to pathological intermediates that polymerize. Structural characterization of these key intermediates is challenging. They are unstable and minimally populated in dynamic equilibria that may be perturbed by many analytical techniques. We have characterized a forme fruste deficiency variant of α(1)-antitrypsin (Lys154Asn) that forms polymers recapitulating the conformer-specific neo-epitope observed in polymers that form in vivo. Lys154Asn α(1)-antitrypsin populates an intermediate ensemble along the polymerization pathway at physiological temperatures. Nuclear magnetic resonance spectroscopy was used to report the structural and dynamic changes associated with this. Our data highlight an interaction network likely to regulate conformational change and do not support the recent contention that the disease-relevant intermediate is substantially unfolded. Conformational disease intermediates may best be defined using powerful but minimally perturbing techniques, mild disease mutants, and physiological conditions.

  11. Epid cine acquisition mode for in vivo dosimetry in dynamic arc radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fidanzio, Andrea [U.O. di Fisica Sanitaria Policlinico A. Gemelli, Universita Cattolica S. Cuore, Rome (Italy)], E-mail: andrea.fidanzio@rm.unicatt.it; Mameli, Alessandra; Placidi, Elisa; Greco, Francesca [U.O. di Fisica Sanitaria Policlinico A. Gemelli, Universita Cattolica S. Cuore, Rome (Italy); Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D' Angelillo, Rolando; Cellini, Francesco; Trodella, Lucio [U.O. di Radioterapia, Universita Campus Bio-Medico, Rome (Italy); Cilla, Savino; Grimaldi, Luca; D' Onofrio, Guido [U.O. di Fisica Sanitaria, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche dell' Universita Cattolica S. Cuore, Campobasso (Italy); Azario, Luigi; Piermattei, Angelo [Istituto di Fisica, Universita Cattolica del S. Cuore, Rome (Italy)

    2008-02-15

    In this paper the cine acquisition mode of an electronic portal imaging device (EPID) has been calibrated and tested to determine the in vivo dose for dynamic conformal arc radiation therapy (DCAT). The EPID cine acquisition mode, that allows a frame acquisition rate of one image every 1.66 s, was studied with a monitor unit rate equal to 100 UM/min. In these conditions good signal stability, {+-}1% (2SD) evaluated during three months, signal reproducibility within {+-}0.8% (2SD) and linearity with dose and dose rate within {+-}1% (2SD) were obtained. The transit signal, S{sub t}, (due to the transmitted beam below the phantom) measured by the EPID cine acquisition mode was used to determine, (i) a set of correlation functions, F(w,L), defined as the ratio between S{sub t} and the dose at half thickness, D{sub m}, measured in solid water phantoms of different thicknesses, w and with square fields of side L, (ii) a set of factors, f(d,L), that take into account the different X-ray scatter contribution from the phantom to the S{sub t} signal as a function of the variation, d, of the air gap between the phantom and the EPID. The reconstruction of the isocenter dose, D{sub iso}, for DCAT was obtained convolving the transit signal values, obtained at different gantry angles, with the respective reconstruction factors determined by a house-made software. The method was tested with cylindrical and anthropomorphic phantoms and the results show that the reconstructed D{sub iso} values can be obtained with an accuracy within {+-}2.5% in cylindrical phantom and within {+-}3.4% for anthropomorphic phantom. In conclusion, the transit dosimetry by EPID was assessed to be adequate to perform DCAT in vivo dosimetry, that is not realizable with the other traditional techniques. Moreover, the method proposed here could be implemented to supply in vivo dose values in real time.

  12. Genus-zero Whitham hierarchies in conformal-map dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Alonso, Luis [Departamento de Fisica Teorica II, Universidad Complutense, E-28040 Madrid (Spain)]. E-mail: luism@fis.ucm.es; Medina, Elena [Departamento de Matematicas, Universidad de Cadiz, E-11510 Puerto Real, Cadiz (Spain)

    2006-10-26

    A scheme for solving quasiclassical string equations is developed to prove that genus-zero Whitham hierarchies describe the deformations of planar domains determined by rational conformal maps. This property is applied in normal matrix models to show that deformations of simply-connected supports of eigenvalues under changes of coupling constants are governed by genus-zero Whitham hierarchies.

  13. NMR detection of slow conformational dynamics in an endonuclease toxin

    Energy Technology Data Exchange (ETDEWEB)

    Whittaker, Sara B.-M.; Boetzel, Ruth; MacDonald, Colin [University of East Anglia, School of Chemical Sciences (United Kingdom); Lian Luyun [Leicester University, Biological NMR Centre (United Kingdom); Pommer, Ansgar J. [University of East Anglia, School of Biological Sciences (United Kingdom); Reilly, Ann; James, Richard; Kleanthous, Colin [Leicester University, Biological NMR Centre (United Kingdom); Moore, Geoffrey R. [University of East Anglia, School of Chemical Sciences (United Kingdom)

    1998-07-15

    The cytotoxic activity of the secreted bacterial toxin colicin E9 is due to a non-specific DNase housed in the C-terminus of the protein. Double-resonance and triple-resonance NMR studies of the 134-amino acid{sup 15} N- and {sup 13}C/{sup 15}N-labelled DNase domain are presented. Extensive conformational heterogeneity was evident from the presence of far more resonances than expected based on the amino acid sequence of the DNase, and from the appearance of chemical exchange cross-peaks in TOCSY and NOESY spectra. EXSY spectra were recorded to confirm that slow chemical exchange was occurring. Unambiguous sequence-specific resonance assignments are presented for one region of the protein, Pro{sup 65}-Asn{sup 72}, which exists in two slowly exchanging conformers based on the identification of chemical exchange cross-peaks in 3D {sup 1}H-{sup 1}H-{sup 15}N EXSY-HSQC, NOESY-HSQC and TOCSY-HSQC spectra, together with C{sup {alpha}} and C{sup {beta}} chemical shifts measured in triple-resonance spectra and sequential NH NOEs. The rates of conformational exchange for backbone amide resonances in this stretch of amino acids, and for the indole NH of either Trp{sup 22} or Trp{sup 58}, were determined from the intensity variation of the appropriate diagonal and chemical exchange cross-peaks recorded in 3D{sup 1} H-{sup 1}H-{sup 15}N NOESY-HSQC spectra. The data fitted a model in which this region of the DNase has two conformers, N{sub A} and N{sub B}, which interchange at 15 {sup o}C with a forward rate constant of 1.61 {+-} 0.5 s{sup -1} and a backward rate constant of 1.05 {+-} 0.5 s{sup -1}. Demonstration of this conformational equilibrium has led to a reappraisal of a previously proposed kinetic scheme describing the interaction of E9 DNase with immunity proteins [Wallis et al. (1995) Biochemistry, 34, 13743-13750 and 13751-13759]. The revised scheme is consistent with the specific inhibitor protein for the E9 DNase, Im9, associating with both the N{sub A} and N{sub B

  14. 'GAIM' - Gas-addition, impedance-matched arc driver. [shock tube gas dynamics

    Science.gov (United States)

    Dannenberg, R. E.

    1980-01-01

    A conceptual view for a GAIM energy/driver system to maximize shock-tube performance through efficient interfacing of the energy source with the gas dynamics of the arc driver is presented. Electrical and arc-chamber requirements are evaluated utilizing two new computer codes. One code calculates the shock wave generated for a selected time rate and magnitude of arc-energy input; the other computes the values of external circuit elements required to produce the selected energy input, with the driver represented as the load element of the electrical discharge circuit. Results indicate that the energy-storage capability and the driver arrangement needed to produce the highest shock Mach number can be achieved by means of driver gas addition and by impedance matching (GAIM). Design criteria are presented for arc energy requirements necessary to produce given shock-wave speeds. Shock velocities as high as the 70 km/sec required for simulating Jovian entry now seem possible in shock-tube operation. Practical implementation of a GAIM system is discussed.

  15. Preparation of carbon nanoparticles by plasma arc discharge under fluidized dynamic equilibrium

    Science.gov (United States)

    Wang, F.; Sun, D. L.; Hong, R. Y.; Kumar, M. R.

    2016-06-01

    Continuous preparation of carbon nanoparticles by dielectric barrier discharge (DBD)-induced non-thermal plasma arc discharge with large spacing in a modified fluidized bed is presented. Discharge arc is generated via the inducement of DBD which provides conductive media in order to realize a large spacing arc discharge. Three kinds of flow conditions defined as full circulation, fluidized dynamic equilibrium, and full collection are determined by the relationship of critical fluidized velocity and the real gas velocity after some modification of the fluidized bed. Movement model of carbon nanoparticles has been proposed to illustrate the flow conditions. A visualized and comprehensive refinement of aggregating processes has been exhibited and proved by high-resolution transmission electron microscopy. Simplified equivalent electrical conductive model of the arc discharge system is successful to generally and perspicuously figure out the discharge process which is impeded by the generated carbon nanoparticles. Effects of flow conditions and flow ratio of carrier gas/carbon source on morphology and yield of nanoparticles have been analyzed by morphology observation and yield calculation along with modeling the process.

  16. Potential for Improved Intelligence Quotient Using Volumetric Modulated Arc Therapy Compared With Conventional 3-Dimensional Conformal Radiation for Whole-Ventricular Radiation in Children

    Energy Technology Data Exchange (ETDEWEB)

    Qi, X. Sharon, E-mail: xqi@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Department of Radiation Oncology, University of Colorado Denver, Aurora, Colorado (United States); Stinauer, Michelle; Rogers, Brion [Department of Radiation Oncology, University of Colorado Denver, Aurora, Colorado (United States); Madden, Jennifer R. [Department of Neuro-Oncology, The Children' s Hospital, Aurora, Colorado (United States); Wilkening, Greta N. [Department of Pediatrics, The Children' s Hospital, Aurora, Colorado (United States); Liu, Arthur K. [Department of Radiation Oncology, University of Colorado Denver, Aurora, Colorado (United States)

    2012-12-01

    Purpose: To compare volumetric modulated arc therapy (VMAT) with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of localized intracranial germinoma. We modeled the effect of the dosimetric differences on intelligence quotient (IQ). Method and Materials: Ten children with intracranial germinomas were used for planning. The prescription doses were 23.4 Gy to the ventricles followed by 21.6 Gy to the tumor located in the pineal region. For each child, a 3D-CRT and full arc VMAT was generated. Coverage of the target was assessed by computing a conformity index and heterogeneity index. We also generated VMAT plans with explicit temporal lobe sparing and with smaller ventricular margin expansions. Mean dose to the temporal lobe was used to estimate IQ 5 years after completion of radiation, using a patient age of 10 years. Results: Compared with the 3D-CRT plan, VMAT improved conformality (conformity index 1.10 vs 1.85), with slightly higher heterogeneity (heterogeneity index 1.09 vs 1.06). The averaged mean doses for left and right temporal lobes were 31.3 and 31.7 Gy, respectively, for VMAT plans and 37.7 and 37.6 Gy for 3D-CRT plans. This difference in mean temporal lobe dose resulted in an estimated IQ difference of 3.1 points at 5 years after radiation therapy. When the temporal lobes were explicitly included in the VMAT optimization, the mean temporal lobe dose was reduced 5.6-5.7 Gy, resulting in an estimated IQ difference of an additional 3 points. Reducing the ventricular margin from 1.5 cm to 0.5 cm decreased mean temporal lobe dose 11.4-13.1 Gy, corresponding to an estimated increase in IQ of 7 points. Conclusion: For treatment of children with intracranial pure germinomas, VMAT compared with 3D-CRT provides increased conformality and reduces doses to normal tissue. This may result in improvements in IQ in these children.

  17. Potential for improved intelligence quotient using volumetric modulated arc therapy compared with conventional 3-dimensional conformal radiation for whole-ventricular radiation in children.

    Science.gov (United States)

    Qi, X Sharon; Stinauer, Michelle; Rogers, Brion; Madden, Jennifer R; Wilkening, Greta N; Liu, Arthur K

    2012-12-01

    To compare volumetric modulated arc therapy (VMAT) with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of localized intracranial germinoma. We modeled the effect of the dosimetric differences on intelligence quotient (IQ). Ten children with intracranial germinomas were used for planning. The prescription doses were 23.4 Gy to the ventricles followed by 21.6 Gy to the tumor located in the pineal region. For each child, a 3D-CRT and full arc VMAT was generated. Coverage of the target was assessed by computing a conformity index and heterogeneity index. We also generated VMAT plans with explicit temporal lobe sparing and with smaller ventricular margin expansions. Mean dose to the temporal lobe was used to estimate IQ 5 years after completion of radiation, using a patient age of 10 years. Compared with the 3D-CRT plan, VMAT improved conformality (conformity index 1.10 vs 1.85), with slightly higher heterogeneity (heterogeneity index 1.09 vs 1.06). The averaged mean doses for left and right temporal lobes were 31.3 and 31.7 Gy, respectively, for VMAT plans and 37.7 and 37.6 Gy for 3D-CRT plans. This difference in mean temporal lobe dose resulted in an estimated IQ difference of 3.1 points at 5 years after radiation therapy. When the temporal lobes were explicitly included in the VMAT optimization, the mean temporal lobe dose was reduced 5.6-5.7 Gy, resulting in an estimated IQ difference of an additional 3 points. Reducing the ventricular margin from 1.5 cm to 0.5 cm decreased mean temporal lobe dose 11.4-13.1 Gy, corresponding to an estimated increase in IQ of 7 points. For treatment of children with intracranial pure germinomas, VMAT compared with 3D-CRT provides increased conformality and reduces doses to normal tissue. This may result in improvements in IQ in these children. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

    Directory of Open Access Journals (Sweden)

    Stella Fabio

    2011-05-01

    Full Text Available Abstract Background Molecular dynamics (MD simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to

  19. Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids

    OpenAIRE

    Moorthy, Balakrishnan S.; Iyer, Lavanya K.; Topp, Elizabeth M.

    2015-01-01

    The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytic...

  20. Conformational Dynamics of o-Fluoro-Substituted Z-Azobenzene.

    Science.gov (United States)

    Rastogi, S K; Rogers, R A; Shi, J; Gao, C; Rinaldi, P L; Brittain, W J

    2015-11-20

    A conformational analysis of o-fluoro Z-azobenzene reveals a slight preference for aromatic C-F/π interaction. Density functional theory (DFT) indicates that the conformation with a C-F/π interaction is preferred by approximately 0.3-0.5 kcal/mol. Ground-state conformations were corroborated with X-ray crystallography. (Z)-Azobenzene (Z-AB) with at least one o-fluoro per ring displays (19)F-(19)F through-space (TS) coupling. 2D J-resolved NMR was used to distinguish through-bond from TS coupling ((TS)JFF). (TS)JFF decreases as the temperature is lowered and the multiplets coalesce into broad singlets. We hypothesize that the coalescence temperature (Tc) corresponds to the barrier for phenyl rotation. The experimentally determined barrier of 8-10 kcal/mol has been qualitatively verified by DFT where transition states with a bisected geometry were identified with zero-point energies of 6-9 kcal/mol relative to ground state. These values are significantly higher that values estimated from previous theoretical studies but lie within a reasonable range for phenyl rotation in hydrocarbon systems.

  1. Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

    DEFF Research Database (Denmark)

    Christensen, I T; Jørgensen, Flemming Steen

    1997-01-01

    A molecular dynamics (MD)-based conformational analysis has been performed on a number of cycloalkanes in order to demonstrate the reliability and generality of MD as a tool for conformational analysis. MD simulations on cyclohexane and a series of methyl-substituted cyclohexanes were performed...... provided 19 out of the 20 most stable conformations found in the MM2 force field. Finally, the general performance of the MD method for conformational analysis is discussed........ A series of methyl-substituted 1,3-dioxanes were investigated at 1000 K, and the number of chair-chair interconversions could be quantitatively correlated to the experimentally determined ring inversion barrier. Similarly, the distribution of sampled minimum-energy conformations correlated with the energy...

  2. Conformational dynamics in substrate-binding domains influences transport in the ABC importer GlnPQ

    NARCIS (Netherlands)

    Gouridis, Giorgos; Schuurman-Wolters, Geesina; Ploetz, Evelyn; Husada, Florence; Vietrov, Ruslan; de Boer, Marijn; Cordes, Thorben; Poolman, Bert

    2015-01-01

    The conformational dynamics in ABC transporters is largely elusive. The ABC importer GlnPQ from Lactococcus lactis has different covalently linked substrate-binding domains (SBDs), thus making it an excellent model system to elucidate the dynamics and role of the SBDs in transport. We demonstrate by

  3. Triggered drug release from dynamic microspheres via a protein conformational change.

    Science.gov (United States)

    King, William J; Pytel, Nicholas J; Ng, Kelvin; Murphy, William L

    2010-06-11

    In this study we formed and characterized dynamic hydrogel microspheres in which a protein conformational change was used to control microsphere volume changes and the release of an encapsulated drug. In particular, a specific biochemical ligand, trifluoperazine, induced calmodulin's nanometer scale conformation change, which translated to a 48.7% microsphere volume decrease. This specific, ligand-induced volume change triggered the release of a model drug, vascular endothelial growth factor (VEGF), at pre-determined times. After release from the microspheres, 85.6 +/- 10.5% of VEGF was in its native conformation. Taken together, these results suggest that protein conformational change could serve as a useful mechanism to control drug release from dynamic hydrogels.

  4. Orientation and conformation of a lipase at an interface studied by molecular dynamics simulations

    DEFF Research Database (Denmark)

    Jensen, Morten Østergaard; Jensen, T.R.; Kjær, Kristian

    2002-01-01

    Electron density profiles calculated from molecular dynamics trajectories are used to deduce the orientation and conformation of Thermomyces lanuginosa lipase and a mutant adsorbed at an air-water interface. It is demonstrated that the profiles display distinct fine structures, which uniquely...... characterize enzyme orientation and conformation. The density profiles are, on the nanosecond timescale, determined by the average enzyme conformation. We outline a Computational scheme that from a single molecular dynamics trajectory allows for extraction of electron density profiles referring to different...... orientations of the lipase relative to an implicit interface. Profiles calculated for the inactive and active conformations of the lipase are compared with experimental electron density profiles measured by x-ray reflectivity for the lipase adsorbed at an air-water interface. The experimental profiles contain...

  5. Extracting Conformational Ensembles of Small Molecules from Molecular Dynamics Simulations: Ampicillin as a Test Case

    Directory of Open Access Journals (Sweden)

    Giuliano Malloci

    2016-01-01

    Full Text Available The accurate and exhaustive description of the conformational ensemble sampled by small molecules in solution, possibly at different physiological conditions, is of primary interest in many fields of medicinal chemistry and computational biology. Recently, we have built an on-line database of compounds with antimicrobial properties, where we provide all-atom force-field parameters and a set of molecular properties, including representative structures extracted from cluster analysis over μs-long molecular dynamics (MD trajectories. In the present work, we used a medium-sized antibiotic from our sample, namely ampicillin, to assess the quality of the conformational ensemble. To this aim, we compared the conformational landscape extracted from previous unbiased MD simulations to those obtained by means of Replica Exchange MD (REMD and those originating from three freely-available conformer generation tools widely adopted in computer-aided drug-design. In addition, for different charge/protonation states of ampicillin, we made available force-field parameters and static/dynamic properties derived from both Density Functional Theory and MD calculations. For the specific system investigated here, we found that: (i the conformational statistics extracted from plain MD simulations is consistent with that obtained from REMD simulations; (ii overall, our MD-based approach performs slightly better than any of the conformer generator tools if one takes into account both the diversity of the generated conformational set and the ability to reproduce experimentally-determined structures.

  6. From Conformal Invariance towards Dynamical Symmetries of the Collisionless Boltzmann Equation

    Directory of Open Access Journals (Sweden)

    Stoimen Stoimenov

    2015-09-01

    Full Text Available Dynamical symmetries of the collisionless Boltzmann transport equation, or Vlasov equation, but under the influence of an external driving force, are derived from non-standard representations of the 2D conformal algebra. In the case without external forces, the symmetry of the conformally-invariant transport equation is first generalized by considering the particle momentum as an independent variable. This new conformal representation can be further extended to include an external force. The construction and possible physical applications are outlined.

  7. Study of conformation and dynamic of surfactant molecules in graphite oxide via NMR

    Energy Technology Data Exchange (ETDEWEB)

    Ai, X.Q. [Jiangsu Second Normal University, College of Physics and Electronic Engineering, Nanjing (China); Ma, L.G. [Nanjing Xiaozhuang University, School of Electronic Engineering, Nanjing (China)

    2016-08-15

    The conformation and dynamic of surfactant in graphite oxide (GO) was investigated by solid-state {sup 13}C magic-angle-spinning NMR and {sup 1}H-{sup 13}C cross-polarization/magic-angle-spinning NMR spectra. The conformation ordering of the alkyl chains in the confined system shows strong dependence on its orientation. While the alkyl chains parallel to the GO layer in lateral monolayer arrangement are in gauche conformation in addition to a small amount of all-trans conformation, those with orientation radiating away from the GO in paraffin bilayer arrangement is in all-trans conformation in addition to some gauche conformation even though high-order diffraction peaks appears. NMR results suggest that the least mobile segment is located at the GO-surfactant interface corresponding to the N-methylene group. Further from it, the mobility of the alkyl chain increases. The terminal methyl and N-methyl carbon groups have the highest mobile. The chains in all-trans conformational state are characterized as more rigid than chains with gauche conformation; each segment of the confined alkyl chains with the lateral monolayer arrangement exhibits less mobility as compared to that with the paraffin bilayer arrangement. (orig.)

  8. Single arc volumetric-modulated arc therapy is sufficient for nasopharyngeal carcinoma: a dosimetric comparison with dual arc VMAT and dynamic MLC and step-and-shoot intensity-modulated radiotherapy

    OpenAIRE

    NING, ZHONG-HUA; Mu, Jin-Ming; Jin, Jian-Xue; Li, Xiao-Dong; LI, QI-LIN; GU, WEN-DONG; Huang, Jin; Han, Yang; PEI, HONG-LEI

    2013-01-01

    Background The performance of single arc VMAT (VMAT1) for nasopharyngeal carcinoma (NPC) on the Axesse linac has not been well described in previous studies. The purpose of this study is to assess the feasibility of VMAT1 for NPC by comparing the dosimetry, delivery efficiency, and accuracy with dual arc VMAT (VMAT2), dynamic MLC intensity-modulated radiotherapy (dIMRT), and step-and-shoot intensity-modulated radiotherapy (ssIMRT). Methods Twenty consecutive patients with non-metastatic NPC w...

  9. Conformational plasticity and dynamics in the generic protein folding catalyst SlyD unraveled by single-molecule FRET.

    Science.gov (United States)

    Kahra, Dana; Kovermann, Michael; Löw, Christian; Hirschfeld, Verena; Haupt, Caroline; Balbach, Jochen; Hübner, Christian Gerhard

    2011-08-26

    The relation between conformational dynamics and chemistry in enzyme catalysis recently has received increasing attention. While, in the past, the mechanochemical coupling was mainly attributed to molecular motors, nowadays, it seems that this linkage is far more general. Single-molecule fluorescence methods are perfectly suited to directly evidence conformational flexibility and dynamics. By labeling the enzyme SlyD, a member of peptidyl-prolyl cis-trans isomerases of the FK506 binding protein type with an inserted chaperone domain, with donor and acceptor fluorophores for single-molecule fluorescence resonance energy transfer, we directly monitor conformational flexibility and conformational dynamics between the chaperone domain and the FK506 binding protein domain. We find a broad distribution of distances between the labels with two main maxima, which we attribute to an open conformation and to a closed conformation of the enzyme. Correlation analysis demonstrates that the conformations exchange on a rate in the 100 Hz range. With the aid from Monte Carlo simulations, we show that there must be conformational flexibility beyond the two main conformational states. Interestingly, neither the conformational distribution nor the dynamics is significantly altered upon binding of substrates or other known binding partners. Based on these experimental findings, we propose a model where the conformational dynamics is used to search the conformation enabling the chemical step, which also explains the remarkable substrate promiscuity connected with a high efficiency of this class of peptidyl-prolyl cis-trans isomerases.

  10. Real-time observation of the conformational dynamics of mitochondrial Hsp70 by spFRET.

    Science.gov (United States)

    Sikor, Martin; Mapa, Koyeli; von Voithenberg, Lena Voith; Mokranjac, Dejana; Lamb, Don C

    2013-05-29

    The numerous functions of the important class of molecular chaperones, heat shock proteins 70 (Hsp70), rely on cycles of intricate conformational changes driven by ATP-hydrolysis and regulated by cochaperones and substrates. Here, we used Förster resonance energy transfer to study the conformational dynamics of individual molecules of Ssc1, a mitochondrial Hsp70, in real time. The intrinsic dynamics of the substrate-binding domain of Ssc1 was observed to be uncoupled from the dynamic interactions between substrate- and nucleotide-binding domains. Analysis of the fluctuations in the interdomain separation revealed frequent transitions to a nucleotide-free state. The nucleotide-exchange factor Mge1 did not induce ADP release, as expected, but rather facilitated binding of ATP. These results indicate that the conformational cycle of Ssc1 is more elaborate than previously thought and provide insight into how the Hsp70s can perform a wide variety of functions.

  11. Molecular modeling of the conformational dynamics of the cellular prion protein

    Science.gov (United States)

    Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

    2014-03-01

    Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

  12. Conformational flexibility and structural dynamics in GPCR-mediated G protein activation: a perspective

    Science.gov (United States)

    Preininger, Anita M.; Meiler, Jens; Hamm, Heidi

    2013-01-01

    Structure and dynamics of G proteins and their cognate receptors, both alone and in complex, are becoming increasingly accessible to experimental techniques. Understanding the conformational changes and timelines which govern these changes can lead to new insights into the processes of ligand binding and associated G protein activation. Experimental systems may involve the use of, or otherwise stabilize, non-native environments. This can complicate our understanding of structural and dynamical features of processes such as the ionic lock, Tryptophan toggle, and G protein flexibility. While elements in the receptor’s transmembrane helices and the C-terminal α5 helix of Gα undergo well defined structural changes, regions subject to conformational flexibility may be important in fine-tuning the interactions between activated receptors and G proteins. The pairing of computational and experimental approaches will continue to provide powerful tools to probe the conformation and dynamics of receptor-mediated G protein activation. PMID:23602809

  13. Characterization of slow conformational dynamics in solids: dipolar CODEX

    Energy Technology Data Exchange (ETDEWEB)

    Li Wenbo; McDermott, Ann E. [Columbia University, Department of Chemistry (United States)], E-mail: aem5@columbia.edu

    2009-09-15

    A solid state NMR experiment is introduced for probing relatively slow conformational exchange, based on dephasing and refocusing dipolar couplings. The method is closely related to the previously described Centerband-Only Detection of Exchange or CODEX experiment. The use of dipolar couplings for this application is advantageous because their values are known a priori from molecular structures, and their orientations and reorientations relate in a simple way to molecular geometry and motion. Furthermore the use of dipolar couplings in conjunction with selective isotopic enrichment schemes is consistent with selection for unique sites in complex biopolymers. We used this experiment to probe the correlation time for the motion of {sup 13}C, {sup 15}N enriched urea molecules within their crystalline lattice.

  14. Characterization of slow conformational dynamics in solids: dipolar CODEX.

    Science.gov (United States)

    Li, Wenbo; McDermott, Ann E

    2009-09-01

    A solid state NMR experiment is introduced for probing relatively slow conformational exchange, based on dephasing and refocusing dipolar couplings. The method is closely related to the previously described Centerband-Only Detection of Exchange or CODEX experiment. The use of dipolar couplings for this application is advantageous because their values are known a priori from molecular structures, and their orientations and reorientations relate in a simple way to molecular geometry and motion. Furthermore the use of dipolar couplings in conjunction with selective isotopic enrichment schemes is consistent with selection for unique sites in complex biopolymers. We used this experiment to probe the correlation time for the motion of (13)C, (15)N enriched urea molecules within their crystalline lattice.

  15. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    Science.gov (United States)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

    2016-07-01

    The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of peptide conformations. These findings are consistent with experimental results, and give a molecular level interpretation for the reduced cytotoxicity of Vpr13-33 to some extent upon graphene exposure. Meanwhile, this study provides some significant insights into the detailed mechanism of graphene-induced protein conformation transition.

  16. Conformational dynamics of ligand-dependent alternating access in LeuT.

    Science.gov (United States)

    Kazmier, Kelli; Sharma, Shruti; Quick, Matthias; Islam, Shahidul M; Roux, Benoît; Weinstein, Harel; Javitch, Jonathan A; McHaourab, Hassane S

    2014-05-01

    The leucine transporter (LeuT) from Aquifex aeolicus is a bacterial homolog of neurotransmitter/sodium symporters (NSSs) that catalyze reuptake of neurotransmitters at the synapse. Crystal structures of wild-type and mutants of LeuT have been interpreted as conformational states in the coupled transport cycle. However, the mechanistic identities inferred from these structures have not been validated, and the ligand-dependent conformational equilibrium of LeuT has not been defined. Here, we used distance measurements between spin-label pairs to elucidate Na(+)- and leucine-dependent conformational changes on the intracellular and extracellular sides of the transporter. The results identify structural motifs that underlie the isomerization of LeuT between outward-facing, inward-facing and occluded states. The conformational changes reported here present a dynamic picture of the alternating-access mechanism of LeuT and NSSs that is different from the inferences reached from currently available structural models.

  17. Allostery and conformational dynamics in cAMP-binding acyltransferases.

    Science.gov (United States)

    Podobnik, Marjetka; Siddiqui, Nida; Rebolj, Katja; Nambi, Subhalaxmi; Merzel, Franci; Visweswariah, Sandhya S

    2014-06-06

    Mycobacteria harbor unique proteins that regulate protein lysine acylation in a cAMP-regulated manner. These lysine acyltransferases from Mycobacterium smegmatis (KATms) and Mycobacterium tuberculosis (KATmt) show distinctive biochemical properties in terms of cAMP binding affinity to the N-terminal cyclic nucleotide binding domain and allosteric activation of the C-terminal acyltransferase domain. Here we provide evidence for structural features in KATms that account for high affinity cAMP binding and elevated acyltransferase activity in the absence of cAMP. Structure-guided mutational analysis converted KATms from a cAMP-regulated to a cAMP-dependent acyltransferase and identified a unique asparagine residue in the acyltransferase domain of KATms that assists in the enzymatic reaction in the absence of a highly conserved glutamate residue seen in Gcn5-related N-acetyltransferase-like acyltransferases. Thus, we have identified mechanisms by which properties of similar proteins have diverged in two species of mycobacteria by modifications in amino acid sequence, which can dramatically alter the abundance of conformational states adopted by a protein.

  18. Conformational Dynamics and Antigenicity in the Disordered Malaria Antigen Merozoite Surface Protein 2

    Science.gov (United States)

    Andrew, Dean; Krishnarjuna, Bankala; Nováček, Jiří; Žídek, Lukáš; Sklenář, Vladimír; Richards, Jack S.; Beeson, James G.; Anders, Robin F.; Norton, Raymond S.

    2015-01-01

    Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design. PMID:25742002

  19. Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2.

    Directory of Open Access Journals (Sweden)

    Christopher A MacRaild

    Full Text Available Merozoite surface protein 2 (MSP2 of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27 using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.

  20. Conformal Dynamics for TeV Physics and Cosmology

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2009-01-01

    We introduce the topic of dynamical breaking of the electroweak symmetry and its link to unparticle physics and cosmology. The knowledge of the phase diagram of strongly coupled theories plays a fundamental role when trying to construct viable extensions of the standard model (SM). Therefore we...

  1. Conformational dynamics in substrate-binding domains influences transport in the ABC importer GlnPQ.

    Science.gov (United States)

    Gouridis, Giorgos; Schuurman-Wolters, Gea K; Ploetz, Evelyn; Husada, Florence; Vietrov, Ruslan; de Boer, Marijn; Cordes, Thorben; Poolman, Bert

    2015-01-01

    The conformational dynamics in ABC transporters is largely elusive. The ABC importer GlnPQ from Lactococcus lactis has different covalently linked substrate-binding domains (SBDs), thus making it an excellent model system to elucidate the dynamics and role of the SBDs in transport. We demonstrate by single-molecule spectroscopy that the two SBDs intrinsically transit from open to closed ligand-free conformation, and the proteins capture their amino acid ligands via an induced-fit mechanism. High-affinity ligands elicit transitions without changing the closed-state lifetime, whereas low-affinity ligands dramatically shorten it. We show that SBDs in the closed state compete for docking onto the translocator, but remarkably the effect is strongest without ligand. We find that the rate-determining steps depend on the SBD and the amino acid transported. We conclude that the lifetime of the closed conformation controls both SBD docking to the translocator and substrate release.

  2. Dosimetric comparison of intensity modulated radiosurgery with dynamic conformal arc radiosurgery for small cranial lesions

    Directory of Open Access Journals (Sweden)

    Juan F Calvo-Ortega

    2016-01-01

    Conclusions: We have shown that IMRS provides the dosimetric advantages compared with DCARS. Based on the dosimetric findings in this study, fixed gantry IMRS technique can be adopted as a standard procedure for cranial SRS when micro-MLC technology is not available on the linear accelerator.

  3. Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy.

    Science.gov (United States)

    Deplazes, Evelyne; Begg, Stephanie L; van Wonderen, Jessica H; Campbell, Rebecca; Kobe, Bostjan; Paton, James C; MacMillan, Fraser; McDevitt, Christopher A; O'Mara, Megan L

    2015-12-01

    Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellular environment. Pneumococcal surface antigen A (PsaA) is the primary Mn(2+)-recruiting protein of the human pathogen Streptococcus pneumoniae and is essential for its in vivo colonization and virulence. The recently reported high-resolution structures of metal-free and metal-bound PsaA have provided the first insights into the mechanism of PsaA-facilitated metal binding. However, the conformational dynamics of metal-free PsaA in solution remain unknown. Here, we use continuous wave electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations to study the relative flexibility of the structural domains in metal-free PsaA and its distribution of conformations in solution. The results show that the crystal structure of metal-free PsaA is a good representation of the dominant conformation in solution, but the protein also samples structurally distinct conformations that are not captured by the crystal structure. Further, these results suggest that the metal binding site is both larger and more solvent exposed than indicated by the metal-free crystal structure. Collectively, this study provides atomic-resolution insight into the conformational dynamics of PsaA prior to metal binding and lays the groundwork for future EPR and MD based studies of PsaA in solution.

  4. Conformation of Randomly Sulfonated Pentablock Ionomers in Dilute Solution: Molecular Dynamic Simulation Study

    Science.gov (United States)

    Aryal, Dipak; Perahia, Dvora; Grest, Gary S.

    2011-03-01

    As part of our efforts to define the factors that control the structure and dynamics of structures ionic polymers, the conformation of a pentablock copolymer that consists of randomly sulfonated polystyrene, an ionomeric block, bound to poly-ethylene-r-propylene end caped by poly-t-butylstyrene has been studied in dilute solutions using molecular dynamic simulations. Multi-block copolymers offer a means to tailor several properties into one molecule, taking advantage of their rich phase diagram together with unique properties of specific blocks. We varied the solvent quality for the different blocks and followed the changes in conformation. The spatial configuration of the pentablock as well as the dynamics of the polymer was studied. We find that, independent on the solvent, the higher the sulfonation level, the lower Rg . The static and dynamic structure factors were calculated and compared in an implicit poor solvent, water and a common solvent. These data are compared with results obtained from neutron scattering.

  5. Dynamic Conformations of Nucleosome Arrays in Solution from Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Steven C. [George Washington Univ., Washington, DC (United States)

    2016-01-31

    We set out to determine quantitative information regarding the dynamic conformation of nucleosome arrays in solution using experimental SAXS. Toward this end, we developed a CG simulation algorithm for dsDNA which rapidly generates ensembles of structures through Metropolis MC sampling of a Markov chain.

  6. Applications of the Local Mode Model to CH Bond Length Changes, Molecular Conformations and Vibrational Dynamics

    OpenAIRE

    Henry, Bryan R.; Gough, Kathleen M.

    1983-01-01

    The theoretical basis for the local mode model is reviewed. The model is applied to gas phase overtone spectra of aromatic molecules to investigate both substituent induced CH bond length changes and conformationally inequivalent hydrogens. The dynamic implications of the local mode model are discussed.

  7. DNA polymerase conformational dynamics and the role of fidelity-conferring residues: Insights from computational simulations

    Directory of Open Access Journals (Sweden)

    Massimiliano eMeli

    2016-05-01

    Full Text Available Herein we investigate the molecular bases of DNA polymerase I conformational dynamics that underlie the replication fidelity of the enzyme. Such fidelity is determined by conformational changes that promote the rejection of incorrect nucleotides before the chemical ligation step. We report a comprehensive atomic resolution study of wild type and mutant enzymes in different bound states and starting from different crystal structures, using extensive molecular dynamics (MD simulations that cover a total timespan of ~ 5 microseconds. The resulting trajectories are examined via a combination of novel methods of internal dynamics and energetics analysis, aimed to reveal the principal molecular determinants for the (destabilization of a certain conformational state. Our results show that the presence of fidelity-decreasing mutations or the binding of incorrect nucleotides in ternary complexes tend to favor transitions from closed towards open structures, passing through an ensemble of semi-closed intermediates. The latter ensemble includes the experimentally observed ajar conformation which, consistent with previous experimental observations, emerges as a molecular checkpoint for the selection of the correct nucleotide to incorporate. We discuss the implications of our results for the understanding of the relationships between the structure, dynamics and function of DNA polymerase I at the atomistic level.

  8. Is DNA a nonlinear dynamical system where solitary conformational waves are possible?

    Indian Academy of Sciences (India)

    Ludmila V Yakushevich

    2001-09-01

    DNA is considered as a nonlinear dynamical system in which solitary conformational waves can be excited. The history of the approach, the main results, and arguments in favour and against are presented. Perspectives are discussed pertaining to studies of DNA’s nonlinear properties.

  9. Beyond Crystallography: Investigating the Conformational Dynamics of the Purine Riboswitch

    Science.gov (United States)

    Stoddard, Colby D.; Batey, Robert T.

    Riboswitches are structured elements located in the 5'-untranslated regions of numerous bacterial mRNAs that serve to regulate gene expression via their ability to specifically bind metabolites. The purine riboswitch ligand-binding domain has emerged as an important model system for investigating the relationship between RNA structure and function. Directed by NMR and crystallographically generated structures of this RNA, a variety of biophysical and biochemical techniques have been utilized to understand its dynamic nature. In this review, we describe these various approaches and what they reveal about the purine riboswitch.

  10. CCR5 conformations are dynamic and modulated by localization, trafficking and G protein association.

    Directory of Open Access Journals (Sweden)

    Ayanna J Flegler

    Full Text Available CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages of infection. Efficient HIV-1 entry requires a series of processes, many dependent on the conformational state of both viral envelope protein and cellular receptor. Monoclonal antibodies (MAbs are able to identify different CCR5 conformations, allowing for their use as probes to distinguish CCR5 populations. Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used such HIV-1-restricting MAbs to probe the relation between localization, trafficking and G protein association for individual CCR5 conformations. We find that CCR5 conformations not only exhibit different localization and abundance patterns throughout the cell, but that they also display distinct sensitivities to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1 inhibitory mechanisms, we also illustrate that responses to ligand engagement are conformation-specific. Additionally, we provide supporting evidence for the select sensitivity of conformations to G protein association. Characterizing the link between the function and dynamics of CCR5 populations has implications for understanding their selective targeting by HIV-1 and for the development of inhibitors that will block CCR5 utilization by the virus.

  11. CCR5 conformations are dynamic and modulated by localization, trafficking and G protein association.

    Science.gov (United States)

    Flegler, Ayanna J; Cianci, Gianguido C; Hope, Thomas J

    2014-01-01

    CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages of infection. Efficient HIV-1 entry requires a series of processes, many dependent on the conformational state of both viral envelope protein and cellular receptor. Monoclonal antibodies (MAbs) are able to identify different CCR5 conformations, allowing for their use as probes to distinguish CCR5 populations. Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used such HIV-1-restricting MAbs to probe the relation between localization, trafficking and G protein association for individual CCR5 conformations. We find that CCR5 conformations not only exhibit different localization and abundance patterns throughout the cell, but that they also display distinct sensitivities to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1 inhibitory mechanisms, we also illustrate that responses to ligand engagement are conformation-specific. Additionally, we provide supporting evidence for the select sensitivity of conformations to G protein association. Characterizing the link between the function and dynamics of CCR5 populations has implications for understanding their selective targeting by HIV-1 and for the development of inhibitors that will block CCR5 utilization by the virus.

  12. Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

  13. Conformal Dynamics for TeV Physics and Cosmology

    CERN Document Server

    Sannino, Francesco

    2009-01-01

    We introduce the topic of dynamical breaking of the electroweak symmetry and its link to unparticle physics and cosmology. The knowledge of the phase diagram of strongly coupled theories plays a fundamental role when trying to construct viable extensions of the standard model (SM). Therefore we present the state-of-the-art of the phase diagram for SU, Sp and SO gauge theories with fermionic matter transforming according to arbitrary representations of the underlying gauge group. We summarize several analytic methods used recently to acquire information about these gauge theories. We also provide new results for the phase diagram of the generalized Bars-Yankielowicz and Georgi-Glashow chiral gauge theories. These theories have been used for constructing grand unified models and have been the template for models of extended technicolor interactions. To gain information on the phase diagram of chiral gauge theories we will introduce a novel all orders beta function for chiral gauge theories. This permits the fir...

  14. Fingerprint of a submerged-arc Furnace. Optimising energy consumption through data mining, dynamic modelling and computational fluid dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Scheepers, E.

    2008-06-26

    This study imparts a scientific perception of a phosphorous-producing submerged arc furnace never seen before; a proverbial fingerprint that can improve problem identification, disturbance diagnostics, process prediction, dynamic modelling and model predictive control of this type of furnace. It successfully incorporates accurate, multi-field thermodynamic-, kinetic- and industrial data with computational flow dynamic calculations; thus further unifying the sciences of kinetics and equilibrium thermodynamics. The true power of this study is the extensive and methodical validation that ensures industrially endorsed results. To facilitate all this the author spent six uninterrupted months at an industrial plant (Thermphos International), twice walked inside a cold submerged-arc furnace, gathered and analysed more than thirty-four mineralogical samples, managed an extensive and insightful sampling campaign on the slag streams, performed feed material porosity tests and had thirteen additional temperature probes installed inside the furnace lining. The author also scrutinised over years of industrial data, inspected many industrial drawing and partook in countless valuable conversations with industrial and technical experts to guarantee, not only a valuable scientific contribution, but one that is deep-rooted in authentic engineering principles.

  15. A 4 MV flattening filter-free beam: commissioning and application to conformal therapy and volumetric modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, S W; Rosser, K E; Bedford, J L, E-mail: simon.stevens@nhs.net [Joint Department of Physics, Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT (United Kingdom)

    2011-07-07

    Recent studies have indicated that radiotherapy treatments undertaken on a flattening filter-free (FFF) linear accelerator have a number of advantages over treatments undertaken on a conventional linear accelerator. In addition, 4 MV photon beams may give improved isodose coverage for some treatment volumes at air/tissue interfaces, compared to when utilizing the clinical standard of 6 MV photons. In order to investigate these benefits, FFF beams were established on an Elekta Beam Modulator linear accelerator for 4 MV photons. Commissioning beam data were obtained for open and wedged fields. The measured data were then imported into a treatment planning system and a beam model was commissioned. The beam model was optimized to improve dose calculations at shallow, clinically relevant depths. Following verification, the beam model was utilized in a treatment planning study, including volumetric modulated arc therapy, for a selection of lung, breast/chest wall and larynx patients. Increased dose rates of around 800 MU min{sup -1} were recorded for open fields (relative to 320 MU min{sup -1} for filtered open fields) and reduced head scatter was inferred from output factor measurements. Good agreement between planned and delivered dose was observed in verification of treatment plans. The planning study indicated that with a FFF beam, equivalent (and in some cases improved) isodose profiles could be achieved for small lung and larynx treatment volumes relative to 4 MV filtered treatments. Furthermore, FFF treatments with wedges could be replicated using open fields together with an 'effective wedge' technique and isocentre shift. Clinical feasibility of a FFF beam was therefore demonstrated, with beam modelling, treatment planning and verification being successfully accomplished.

  16. Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.

    Science.gov (United States)

    Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

    2016-07-01

    This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

  17. Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

    Science.gov (United States)

    Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

    2016-05-24

    DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

  18. Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

    Science.gov (United States)

    Wu, Bin

    Neutron scattering and fully atomistic molecular dynamics (MD) are employed to investigate the structural and dynamical properties of polyamidoamine (PAMAM) dendrimers with ethylenediamine (EDA) core under various charge conditions. Regarding to the conformational characteristics, we focus on scrutinizing density profile evolution of PAMAM dendrimers as the molecular charge of dendrimer increases from neutral state to highly charged condition. It should be noted that within the context of small angle neutron scattering (SANS), the dendrimers are composed of hydrocarbon component (dry part) and the penetrating water molecules. Though there have been SANS experiments that studied the charge-dependent structural change of PAMAM dendrimers, their results were limited to the collective behavior of the aforementioned two parts. This study is devoted to deepen the understanding towards the structural responsiveness of intra-molecular polymeric and hydration parts separately through advanced contrast variation SANS data analysis scheme available recently and unravel the governing principles through coupling with MD simulations. Two kinds of acids, namely hydrochloric and sulfuric acids, are utilized to tune the pH condition and hence the molecular charge. As far as the dynamical properties, we target at understanding the underlying mechanism that leads to segmental dynamic enhancement observed from quasielstic neutron scattering (QENS) experiment previously. PAMAM dendrimers have a wealth of potential applications, such as drug delivery agency, energy harvesting medium, and light emitting diodes. More importantly, it is regarded as an ideal system to test many theoretical predictions since dendrimers conjugate both colloid-like globular shape and polymer-like flexible chains. This Ph.D. research addresses two main challenges in studying PAMAM dendrimers. Even though neutron scattering is an ideal tool to study this PAMAM dendrimer solution due to its matching temporal and

  19. Conformational space of clindamycin studied by ab initio and full-atom molecular dynamics.

    Science.gov (United States)

    Kulczycka-Mierzejewska, Katarzyna; Trylska, Joanna; Sadlej, Joanna

    2016-01-01

    Molecular dynamics (MD) simulations allow determining internal flexibility of molecules at atomic level. Using ab initio Born-Oppenheimer molecular dynamics (BOMD), one can simulate in a reasonable time frame small systems with hundreds of atoms, usually in vacuum. With quantum mechanics/molecular mechanics (QM/MM) or full-atom molecular dynamics (FAMD), the influence of the environment can also be simulated. Here, we compare three types of MD calculations: ab initio BOMD, hybrid QM/MM, and classical FAMD. As a model system, we use a small antibiotic molecule, clindamycin, which is one of the lincosamide antibiotics. Clindamycin acquires two energetically stable forms and we investigated the transition between these two experimentally known conformers. We performed 60-ps BOMD simulations in vacuum, 50-ps QM/MM, and 100-ns FAMD in explicit water. The transition between two antibiotic conformers was observed using both BOMD and FAMD methods but was not noted in the QM/MM simulations.

  20. Dynamic UAV-based traffic monitoring under uncertainty as a stochastic arc-inventory routing policy

    Directory of Open Access Journals (Sweden)

    Joseph Y.J. Chow

    2016-10-01

    Full Text Available Given the rapid advances in unmanned aerial vehicles, or drones, and increasing need to monitor at a city level, one of the current research gaps is how to systematically deploy drones over multiple periods. We propose a real-time data-driven approach: we formulate the first deterministic arc-inventory routing problem and derive its stochastic dynamic policy. The policy is expected to be of greatest value in scenarios where uncertainty is highest and costliest, such as city monitoring during major events. The Bellman equation for an approximation of the proposed inventory routing policy is formulated as a selective vehicle routing problem. We propose an approximate dynamic programming algorithm based on Least Squares Monte Carlo simulation to find that policy. The algorithm has been modified so that the least squares dependent variable is defined to be the “expected stock out cost upon the next replenishment”. The new algorithm is tested on 30 simulated instances of real time trajectories over 5 time periods of the selective vehicle routing problem to evaluate the proposed policy and algorithm. Computational results on the selected instances show that the algorithm on average outperforms the myopic policy by 23–28%, depending on the parametric design. Further tests are conducted on classic benchmark arc routing problem instances. The 11-link instance gdb19 (Golden et al., 1983 is expanded into a sequential 15-period stochastic dynamic example and used to demonstrate why a naïve static multi-period deployment plan would not be effective in real networks.

  1. Finding Stable Graphene Conformations from Pull and Release Experiments with Molecular Dynamics

    Science.gov (United States)

    Yamaletdinov, Ruslan D.; Pershin, Yuriy V.

    2017-01-01

    Here, we demonstrate that stable conformations of graphene nanoribbons can be identified using pull and release experiments, when the stretching force applied to a single-layer graphene nanoribbon is suddenly removed. As it is follows from our numerical experiments performed by means of molecular dynamics simulations, in such experiments, favorable conditions for the creation of folded structures exist. Importantly, at finite temperatures, the process of folding is probabilistic. We have calculated the transition probabilities to folded conformations for a graphene nanoribbon of a selected size. Moreover, the ground state conformation has been identified and it is shown that its type is dependent on the nanoribbon length. We anticipate that the suggested pull and release approach to graphene folding may find applications in the theoretical studies and fabrication of emergent materials and their structures. PMID:28195156

  2. Volumetric-modulated arc radiotherapy for pancreatic malignancies: Dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nabavizadeh, Nima, E-mail: nabaviza@ohsu.edu; Simeonova, Anna O.; Waller, Joseph G.; Romer, Jeanna L.; Monaco, Debra L.; Elliott, David A.; Tanyi, James A.; Fuss, Martin; Thomas, Charles R.; Holland, John M.

    2014-10-01

    Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity-modulated radiotherapy (IMRT), both of which deliver highly conformal dose distributions. Studies have shown the superiority of VMAT and IMRT in comparison with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy. A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45 Gy to a large field followed by a reduced-volume 8-fraction external beam boost to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from 1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and VMAT CI deviations from 1.0 for the large-field and the boost plans were equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037, respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177; p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean number of MUs per fraction was significantly lower for VMAT for both the large-field and the boost plans. VMAT delivery time was less than 3 minutes compared with 8 minutes for IMRT. Although no statistically significant dose reduction to the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in the volumes of the 100% isodose line for the large-field plans. Dose escalation to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

  3. Parallel cascade selection molecular dynamics for efficient conformational sampling and free energy calculation of proteins

    Science.gov (United States)

    Kitao, Akio; Harada, Ryuhei; Nishihara, Yasutaka; Tran, Duy Phuoc

    2016-12-01

    Parallel Cascade Selection Molecular Dynamics (PaCS-MD) was proposed as an efficient conformational sampling method to investigate conformational transition pathway of proteins. In PaCS-MD, cycles of (i) selection of initial structures for multiple independent MD simulations and (ii) conformational sampling by independent MD simulations are repeated until the convergence of the sampling. The selection is conducted so that protein conformation gradually approaches a target. The selection of snapshots is a key to enhance conformational changes by increasing the probability of rare event occurrence. Since the procedure of PaCS-MD is simple, no modification of MD programs is required; the selections of initial structures and the restart of the next cycle in the MD simulations can be handled with relatively simple scripts with straightforward implementation. Trajectories generated by PaCS-MD were further analyzed by the Markov state model (MSM), which enables calculation of free energy landscape. The combination of PaCS-MD and MSM is reported in this work.

  4. Conformal house

    DEFF Research Database (Denmark)

    Ryttov, Thomas Aaby; Sannino, Francesco

    2010-01-01

    fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

  5. Calculation of the Dynamic Characteristics of an Electric Arc Subjected to Forced Extinction

    Science.gov (United States)

    Nekrasov, S. A.

    2016-11-01

    Models and methods of calculating the currents in a free-burning arc and in an arc in an arc chute with magnetic blow and the voltages across them in the process of their extinction are considered. A comparison of calculation and experimental data has been performed.

  6. Parallel Cascade Selection Molecular Dynamics (PaCS-MD) to generate conformational transition pathway.

    Science.gov (United States)

    Harada, Ryuhei; Kitao, Akio

    2013-07-21

    Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

  7. Conformal optical design with combination of static and dynamic aberration corrections

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Li Lin; Huang Yi-Fan; Liu Jia-Guo

    2009-01-01

    Conformal domes that are shaped to meet aerodynamic requirements can increase range and speed for the host platform. Because these domes typically deviate greatly from spherical surface descriptions, a variety of aberrations are induced which vary with the field-of-regard (FOR) angle. A system for correcting optical aberrations created by a conformal dome has an outer surface and an inner surface. Optimizing the inner surface is regard as static aberration correction. A deformable mirror is placed at the position of the secondary mirror in the two-mirror all reflective imaging system, which is the dynamic aberration correction. An ellipsoidal MgF2 conformal dome with a fineness ratio of 1.0 is designed as an example. The FOR angle is 00°-30°, and the design wavelength is 4 μm. After the optimization at 7zoom positions by using the design tools Code V, the root-mean-square (RMS) spot size is reduced to approximately 0.99 to 1.48 times the diffraction limit. The design results show that the performances of the conformal optical systems can be greatly improved by the combination of the static correction and the dynamic correction.

  8. Ubiquitin dynamics in complexes reveal molecular recognition mechanisms beyond induced fit and conformational selection.

    Directory of Open Access Journals (Sweden)

    Jan H Peters

    Full Text Available Protein-protein interactions play an important role in all biological processes. However, the principles underlying these interactions are only beginning to be understood. Ubiquitin is a small signalling protein that is covalently attached to different proteins to mark them for degradation, regulate transport and other functions. As such, it interacts with and is recognised by a multitude of other proteins. We have conducted molecular dynamics simulations of ubiquitin in complex with 11 different binding partners on a microsecond timescale and compared them with ensembles of unbound ubiquitin to investigate the principles of their interaction and determine the influence of complex formation on the dynamic properties of this protein. Along the main mode of fluctuation of ubiquitin, binding in most cases reduces the conformational space available to ubiquitin to a subspace of that covered by unbound ubiquitin. This behaviour can be well explained using the model of conformational selection. For lower amplitude collective modes, a spectrum of zero to almost complete coverage of bound by unbound ensembles was observed. The significant differences between bound and unbound structures are exclusively situated at the binding interface. Overall, the findings correspond neither to a complete conformational selection nor induced fit scenario. Instead, we introduce a model of conformational restriction, extension and shift, which describes the full range of observed effects.

  9. Exploring the conformational space of chromatin fibers and their stability by numerical dynamic phase diagrams.

    Science.gov (United States)

    Stehr, René; Schöpflin, Robert; Ettig, Ramona; Kepper, Nick; Rippe, Karsten; Wedemann, Gero

    2010-03-17

    The three-dimensional structure of chromatin affects DNA accessibility and is therefore a key regulator of gene expression. However, the path of the DNA between consecutive nucleosomes, and the resulting chromatin fiber organization remain controversial. The conformational space available for the folding of the nucleosome chain has been analytically described by phase diagrams with a two-angle model, which describes the chain trajectory by a DNA entry-exit angle at the nucleosome and a torsion angle between consecutive nucleosomes. Here, a novel type of numerical phase diagrams is introduced that relates the geometric phase space to the energy associated with a given chromatin conformation. The resulting phase diagrams revealed differences in the energy landscape that reflect the probability of a given conformation to form in thermal equilibrium. Furthermore, we investigated the effects of entropy and additional degrees of freedom in the dynamic phase diagrams by performing Monte Carlo simulations of the initial chain trajectories. Using our approach, we were able to demonstrate that conformations that initially were geometrically impossible could evolve into energetically favorable states in thermal equilibrium due to DNA bending and torsion. In addition, dynamic phase diagrams were applied to identify chromatin fibers that reflect certain experimentally determined features.

  10. SU-E-T-140: Dynamic Wave Arc Trajectory Verification Using KV X-Ray Fluoroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Burghelea, M; Poels, K; Depuydt, T; Tournel, K; Verellen, D; De Ridder, M [Universitair Ziekenhuis Brussel, Jette, Brussels (Belgium)

    2014-06-01

    Purpose: Purpose: This study investigates the geometric accuracy of simultaneous Gantry/Ring rotation during Dynamic Wave Arc (DWA) delivery. Methods: The Vero SBRT system consists of a 6MV LINAC mounted on an O-ring gantry that can rotate around the vertical axis (±60°), similar to couch rotation on C-arm gantries. To provide CBCT and fluoroscopy imaging functionalities, two orthogonal kV imaging units are attached to the O-ring at −45°/+45° from the beam axis.Dynamic Wave Arc maximizes Vero's motion capabilities by employing synchronized gantry and ring motion on a complex non-coplanar trajectory in combination with aperture based optimized MLC segments.Four wave arc trajectories (T1-4) were delivered using a cubic phantom with a configuration of five lead beads. O-ring gantry position information was retrieved through continuous dual-source kV X-ray image acquisition during DWA. An in-house algorithm read in the image set, extracted the projected marker positions and determined the angulation through reconstruction of the beam source position. The geometric error was quantified as the distance between the independently detected positions from kV-images and reference trajectory derived from the treatment plan in the Ring-Gantry space. Results: The average displacement between the 3D gantry/ring positions reconstructed from the fluoroscopy images and the reference trajectory was 0.346 mm (SD 0,171) for T1. A mean offset of 0.348 mm (SD 0,182) and 0.357 mm (SD 0.194) was observed for trajectory T2(2segmens) and T3(4segments), respectively. The saw shape T4 presented a mean geometric error of 0.363 (SD 0.156). The overall systematic error of 0.350 was caused by the difference between planned reference trajectory created by linear interpolation between CP, and the machine delivery following a spline curve. Conclusion: An independent geometric QA approach has been developed for DWA delivery verification, successfully applied on diverse trajectories and

  11. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian, E-mail: jianzhou@scut.edu.cn

    2016-07-30

    Graphical abstract: Preferential adsorption of Vpr13-33 on graphene accompanied by early conformational change from α-helix to β-sheet structures was observed by molecular simulations. This work presents the molecular mechanism of graphene-induced peptide conformational alteration and sheds light on developing graphene-based materials to inhibit HIV. - Highlights: • Graphene induced early structural transition of Vpr13-33 is studied by MD simulations. • Both π-π stacking and hydrophobic interactions orchestrate the peptide adsorption. • Vpr has an increased propensity of β-sheet content on graphene surface. • To develop graphene-based materials to inhibit HIV is possible. - Abstract: The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of

  12. Study conformational dynamics of intrinsically disordered protein by PET-FCS (Conference Presentation)

    Science.gov (United States)

    Enderlein, Joerg; Zhou, Man; Van, Qui; Gregor, Ingo

    2016-02-01

    Intrinsically disordered proteins (IDP) form a large and functionally important class of proteins that lack an ordered three-dimensional structure. IDPs play an important role in cell signaling, transcription, or chromatin remodeling. The discovery of IDPs has challenged the traditional paradigm of protein structure which states that protein function depends on a well-defined three-dimensional structure. Due to their high conformational flexibility and the lack of ordered secondary structure, it is challenging to study the flexible structure, dynamics and energetics of these proteins with conventional methods. In our work, we employ photoinduced electron transfer (PET) combined with fluorescence correlation spectroscopy (FCS) for studying the conformational dynamics of one specific class of IDPs: phenylalanine-glycine rich protein domains (FG repeats) which are dominant building blocks within the pore of nuclear pore complexes. Nuclear pore complexes are large protein assemblies that cross the nuclear envelope and form selective barrier, which regulate bidirectional exchange between nucleus and cytoplasm.

  13. Collective dynamics of belief evolution under cognitive coherence and social conformity

    CERN Document Server

    Rodriguez, Nathaniel; Ahn, Yong-Yeol

    2015-01-01

    Human history has been marked by social instability and conflict, often driven by the irreconcilability of opposing sets of beliefs, ideologies, and religious dogmas. The dynamics of belief systems has been studied mainly from two distinct perspectives, namely how cognitive biases lead to individual belief rigidity and how social influence leads to social conformity. Here we propose a unifying framework that connects cognitive and social forces together in order to study the dynamics of societal belief evolution. Each individual is endowed with a network of interacting beliefs that evolves through interaction with other individuals in a social network. The adoption of beliefs is affected by both internal coherence and social conformity. Our framework explains how social instabilities can arise in otherwise homogeneous populations, how small numbers of zealots with highly coherent beliefs can overturn societal consensus, and how belief rigidity protects fringe groups and cults against invasion from mainstream ...

  14. Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure.

    Science.gov (United States)

    Marsh, Joseph A; Teichmann, Sarah A

    2014-02-01

    Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related to local protein flexibility and disorder, large-scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution.

  15. Dynamic fluctuations provide the basis of a conformational switch mechanism in apo cyclic AMP receptor protein.

    Science.gov (United States)

    Aykaç Fas, Burcu; Tutar, Yusuf; Haliloğlu, Türkan

    2013-01-01

    Escherichia coli cyclic AMP Receptor Protein (CRP) undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD) simulations and Gaussian Network Model (GNM). The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra- and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.

  16. Probing the Impact of Local Structural Dynamics of Conformational Epitopes on Antibody Recognition.

    Science.gov (United States)

    Liang, Yu; Guttman, Miklos; Davenport, Thaddeus M; Hu, Shiu-Lok; Lee, Kelly K

    2016-04-19

    Antibody-antigen interactions are governed by recognition of specific residues and structural complementarity between the antigen epitope and antibody paratope. While X-ray crystallography has provided detailed insights into static conformations of antibody-antigen complexes, factors such as conformational flexibility and dynamics, which are not readily apparent in the structures, can also have an impact on the binding event. Here we investigate the contribution of dynamics in the HIV-1 gp120 glycoprotein to antibody recognition of conserved conformational epitopes, including the CD4- and coreceptor-binding sites, and an inner domain site that is targeted by ADCC-active antibodies. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) was used to measure local structural dynamics across a panel of variable loop truncation mutants of HIV-1 gp120, including full-length gp120, ΔV3, ΔV1/V2, and extended core, which includes ΔV1/V2 and V3 loop truncations. CD4-bound full-length gp120 was also examined as a reference state. HDX-MS revealed a clear trend toward an increased level of order of the conserved subunit core resulting from loop truncation. Combined with biolayer interferometry and enzyme-linked immunosorbent assay measurements of antibody-antigen binding, we demonstrate that an increased level of ordering of the subunit core was associated with better recognition by an array of antibodies targeting complex conformational epitopes. These results provide detailed insight into the influence of structural dynamics on antibody-antigen interactions and suggest the importance of characterizing the structural stability of vaccine candidates to improve antibody recognition of complex epitopes.

  17. Dosimetric study of volumetric arc modulation with RapidArc and intensity-modulated radiotherapy in patients with cervical cancer and comparison with 3-dimensional conformal technique for definitive radiotherapy in patients with cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guy, Jean-Baptiste [Department of Radiation Oncology, Institut de Cancérologie de la Loire Lucien Neuwirth, Saint-Priest en Jarez (France); Falk, Alexander T. [Department of Radiation Oncology, Centre Antoine Lacassagne, Nice (France); Auberdiac, Pierre [Department of Radiation Oncology, Clinique Claude Bernard, Albi (France); Cartier, Lysian; Vallard, Alexis [Department of Radiation Oncology, Institut de Cancérologie de la Loire Lucien Neuwirth, Saint-Priest en Jarez (France); Ollier, Edouard [Department of Pharmacology-Toxicology, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Priest en Jarez (France); Trone, Jane-Chloé; Khodri, Moustapha [Department of Radiation Oncology, Institut de Cancérologie de la Loire Lucien Neuwirth, Saint-Priest en Jarez (France); Chargari, Cyrus [Department of Radiation Oncology, Hôpital d’instruction de Armées du Val-de-Grâce, Paris (France); Magné, Nicolas, E-mail: nicolas.magne@icloire.fr [Department of Radiation Oncology, Institut de Cancérologie de la Loire Lucien Neuwirth, Saint-Priest en Jarez (France)

    2016-04-01

    Introduction: For patients with cervical cancer, intensity-modulated radiation therapy (IMRT) improves target coverage and allows dose escalation while reducing the radiation dose to organs at risk (OARs). In this study, we compared dosimetric parameters among 3-dimensional conformal radiotherapy (3D-CRT), “step-and-shoot” IMRT, and volumetric intensity-modulated arc radiotherapy (VMAT) in a series of patients with cervical cancer receiving definitive radiotherapy. Computed tomography (CT) scans of 10 patients with histologically proven cervical cancer treated with definitive radiation therapy (RT) from December 2008 to March 2010 at our department were selected for this study. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated following the guidelines of the Gyn IMRT consortium that included cervix, uterus, parametrial tissues, and the pelvic nodes including presacral. The median age was 57 years (range: 30 to 85 years). All 10 patients had squamous cell carcinoma with Federation of Gynecology and Obstetrics (FIGO) stage IB-IIIB. All patients were treated by VMAT. OAR doses were significantly reduced for plans with intensity-modulated technique compared with 3D-CRT except for the dose to the vagina. Between the 2 intensity-modulated techniques, significant difference was observed for the mean dose to the small intestine, to the benefit of VMAT (p < 0.001). There was no improvement in terms of OARs sparing for VMAT although there was a tendency for a slightly decreased average dose to the rectum: − 0.65 Gy but not significant (p = 0.07). The intensity modulation techniques have many advantages in terms of quality indexes, and particularly OAR sparing, compared with 3D-CRT. Following the ongoing technologic developments in modern radiotherapy, it is essential to evaluate the intensity-modulated techniques on prospective studies of a larger scale.

  18. Dynamic optical aberration correction with adaptive coded apertures techniques in conformal imaging

    Science.gov (United States)

    Li, Yan; Hu, Bin; Zhang, Pengbin; Zhang, Binglong

    2015-02-01

    Conformal imaging systems are confronted with dynamic aberration in optical design processing. In classical optical designs, for combination high requirements of field of view, optical speed, environmental adaption and imaging quality, further enhancements can be achieved only by the introduction of increased complexity of aberration corrector. In recent years of computational imaging, the adaptive coded apertures techniques which has several potential advantages over more traditional optical systems is particularly suitable for military infrared imaging systems. The merits of this new concept include low mass, volume and moments of inertia, potentially lower costs, graceful failure modes, steerable fields of regard with no macroscopic moving parts. Example application for conformal imaging system design where the elements of a set of binary coded aperture masks are applied are optimization designed is presented in this paper, simulation results show that the optical performance is closely related to the mask design and the reconstruction algorithm optimization. As a dynamic aberration corrector, a binary-amplitude mask located at the aperture stop is optimized to mitigate dynamic optical aberrations when the field of regard changes and allow sufficient information to be recorded by the detector for the recovery of a sharp image using digital image restoration in conformal optical system.

  19. Molecular dynamics simulation and conformational analysis of some catalytically active peptides.

    Science.gov (United States)

    Honarparvar, Bahareh; Skelton, Adam A

    2015-04-01

    The design of stable and inexpensive artificial enzymes with potent catalytic activity is a growing field in peptide science. The first step in this design process is to understand the key factors that can affect the conformational preference of an enzyme and correlate them with its catalytic activity. In this work, molecular dynamics simulations in explicit water of two catalytically active peptides (peptide 1: Fmoc-Phe1-Phe2-His-CONH2; peptide 2: Fmoc-Phe1-Phe2-Arg-CONH2) were performed at temperatures of 300, 400, and 500 K. Conformational analysis of these peptides using Ramachandran plots identified the secondary structures of the amino acid residues involved (Phe1, Phe2, His, Arg) and confirmed their conformational flexibility in solution. Furthermore, Ramachandran maps revealed the intrinsic preference of the constituent residues of these compounds for a helical conformation. Long-range interaction distances and radius of gyration (R g) values obtained during 20 ns MD simulations confirmed their tendency to form folded conformations. Results showed a decrease in side-chain (Phe1, Phe2, His ring, and Arg) contacts as the temperature was raised from 300 to 400 K and then to 500 K. Finally, the radial distribution functions (RDF) of the water molecules around the nitrogen atoms in the catalytically active His and Arg residues of peptide 1 and peptide 2 revealed that the strongest water-peptide interaction occurred with the arginine nitrogen atoms in peptide 2. Our results highlight differences in the secondary structures of the two peptides that can be explained by the different arrangement of water molecules around the nitrogen atoms of Arg in peptide 2 as compared to the arrangement of water molecules around the nitrogen atoms of His in peptide 1. The results of this work thus provide detailed insight into peptide conformations which can be exploited in the future design of peptide analogs.

  20. Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin.

    Directory of Open Access Journals (Sweden)

    Ayse Ozlem Aykut

    Full Text Available We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca(2+-CaM. We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca(2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca(2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca(2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength.

  1. Dynamics, OH distributions and UV emission of a gliding arc at various flow-rates investigated by optical measurements

    DEFF Research Database (Denmark)

    Zhu, Jiajian; Sun, Zhiwei; Li, Zhongshan

    2014-01-01

    -state OH were investigated using planar laser-induced fluorescence. The results show that the shape, height, intensity and thickness of ground-state OH distribution vary significantly with air flow rates. Finally, UV emission of the gliding arc is measured using optical emission spectroscopy......We demonstrate a plasma discharge which is generated between two diverging electrodes and extended into a gliding arc in non-equilibrium condition by an air flow at atmospheric pressure. Effects of the air flow rates on the dynamics, ground-state OH distributions and spectral characterization of UV...

  2. Self-assembly, Dynamics and Chirality of Conformational Switches on Metal Surfaces Studied by UHV-STM

    DEFF Research Database (Denmark)

    Nuermaimaiti, Ajiguli

    2013-01-01

    Molecular self-assembly is essential in the bottom-up design of nanostructures. Molecular conformational switches are highly interesting both from the basic science of view to enhance our understanding of molecular dynamics in adsorption systems, and also due to potential applications such as mol......Molecular self-assembly is essential in the bottom-up design of nanostructures. Molecular conformational switches are highly interesting both from the basic science of view to enhance our understanding of molecular dynamics in adsorption systems, and also due to potential applications...... structures formed by the conformational switches and statistical analysis of conformational states, a detailed study of dynamic processes is performed by acquiring time-resolved STM data. Furthermore, one of the possible applications of conformational switches towards inducing chirality in surface assemblies...

  3. EFFECT OF GEAR WIDTH AND HELIX ANGLE ON FACTOR OF DYNAMIC LOAD OF DOUBLE CIRCULAR ARC HELICAL GEARING

    Institute of Scientific and Technical Information of China (English)

    Wu Baolin

    2004-01-01

    Based on theory of mechanical dynamics, meshing characteristic as well as the dynamic model of double circular arc helical gearing, an analysis approach and a computer program have been developed for studying the state of dynamic load and factor of dynamic load of the gearing, the changing situation of dynamic load and dynamic load factor vs some affecting factors such as gear width, helix angle and accuracy grade etc are investigated. A series of conclusions are obtained: ①With the increasing in the values of gear width, the dynamic load factor appears slow decreasing tendency in most region of gear width. ② When the accuracy grades of the gearing are improved, the values of dynamic load factor decrease. ③ The value of dynamic load factor appears a decreasing tendency with the increasing of value of helix angle at the same ratio of critical rotational speed.

  4. Conformational polymorphism of the PrP106-126 peptide in different environments : A molecular dynamics study

    NARCIS (Netherlands)

    Villa, Alessandra; Mark, AE; Saracino, GAA; Cosentino, U; Pitea, D; Moro, G; Salmona, M

    2006-01-01

    Extensive molecular dynamic simulations (similar to 240 ns) have been used to investigate the conformational behavior of PrP106-126 prion peptide in four different environments (water, dimethyl sulfoxide, hexane, and trifluoroethanol) and under both neutral and acidic conditions. The conformational

  5. Radioactive waste combustion / vitrification under arc plasma: thermal and dynamic modelling; Combustion - vitrification de dechets radioactifs par plasma d'arc: modelisation de la thermique et de la dynamique

    Energy Technology Data Exchange (ETDEWEB)

    Barthelemy, B

    2003-07-01

    This thesis concerns the thermal and dynamic modelling for a combustion/vitrification process of surrogate radioactive waste under transferred arc plasma. The writer presents the confinement processes for radioactive waste using arc plasma and the different software used to model theses processes. This is followed by a description of our experimental equipment including a plasma arc reactor and an inductive system allowing the homogenization of glass temperature. A combustion/vitrification test is described. Thermal and material balances were discussed. The temperature fields of plasma arc and the glass frit conductivity are measured. Finally, the writer describes and clarifies the equations solved for the simulations of the electrically plasma arc and the glass melting including the thin layer of glass frit coating the crucible cold walls. The modelling results are presented in the form of spatial distribution of temperature, velocity and volume power... (author)

  6. Radioactive waste combustion-vitrification under arc plasma: thermal and dynamic modelling; Combustion - vitrification de dechets radioactifs par plasma d'arc: modelisation de la thermique et de la dynamique

    Energy Technology Data Exchange (ETDEWEB)

    Barthelemy, B

    2003-06-01

    This thesis concerns the thermal and dynamic modelling for a combustion/vitrification process of surrogate radioactive waste under transferred arc plasma. The writer presents the confinement processes for radioactive waste using arc plasma and the different software used to model theses processes. This is followed by a description of our experimental equipment including a plasma arc reactor and an inductive system allowing the homogenization of glass temperature. A combustion/vitrification test is described. Thermal and material balances were discussed. The temperature fields of plasma arc and the glass frit conductivity are measured. Finally, the writer describes and clarifies the equations solved for the simulations of the electrically plasma arc and the glass melting including the thin layer of glass frit coating the crucible cold walls. The modelling results are presented in the form of spatial distribution of temperature, velocity and voluminal power... (author)

  7. Interdependence of conformational and chemical reaction dynamics during ion assembly in polar solvents.

    Science.gov (United States)

    Ji, Minbiao; Hartsock, Robert W; Sun, Zheng; Gaffney, Kelly J

    2011-10-01

    We have utilized time-resolved vibrational spectroscopy to study the interdependence of the conformational and chemical reaction dynamics of ion assembly in solution. We investigated the chemical interconversion dynamics of the LiNCS ion pair and the (LiNCS)(2) ion-pair dimer, as well as the spectral diffusion dynamics of these ionic assemblies. For the strongly coordinating Lewis base solvents benzonitrile, dimethyl carbonate, and ethyl acetate, we observe Li(+) coordination by both solvent molecules and NCS(-) anions, while the weak Lewis base solvent nitromethane shows no evidence for solvent coordination of Li(+) ions. The strong interaction between the ion-pair dimer structure and the Lewis base solvents leads to ion-pair dimer solvation dynamics that proceed more slowly than the ion-pair dimer dissociation. We have attributed the slow spectral diffusion dynamics to electrostatic reorganization of the solvent molecules coordinated to the Li(+) cations present in the ion-pair dimer structure and concluded that the dissociation of ion-pair dimers depends more critically on longer length scale electrostatic reorganization. This unusual inversion of the conformational and chemical reaction rates does not occur for ion-pair dimer dissociation in nitromethane or for ion pair association in any of the solvents.

  8. Rapid Arc, helical tomotherapy, sliding window intensity modulated radiotherapy and three dimensional conformal radiation for localized prostate cancer: A dosimetric comparison

    Directory of Open Access Journals (Sweden)

    Rajesh A Kinhikar

    2014-01-01

    Full Text Available Objective: The objective of this study was to investigate the potential role of RapidArc (RA compared with helical tomotherapy (HT, sliding window intensity modulated radiotherapy (SW IMRT and three-dimensional conformal radiation therapy (3D CRT for localized prostate cancer. Materials and Methods: Prescription doses ranged from 60 Gy to planning target volume (PTV and 66.25 Gy for clinical target volume prostate (CTV-P over 25-30 fractions. PTV and CTV-P coverage were evaluated by conformity index (CI and homogeneity index (HI. Organ sparing comparison was done with mean doses to rectum and bladder. Results: CI 95 were 1.0 ± 0.01 (RA, 0.99 ± 0.01 (HT, 0.97 ± 0.02 (IMRT, 0.98 ± 0.02 (3D CRT for PTV and 1.0 ± 0.00 (RA, HT, SW IMRT and 3D CRT for CTV-P. HI was 0.11 ± 0.03 (RA, 0.16 ± 0.08 (HT, 0.12 ± 0.03 (IMRT, 0.06 ± 0.01 (3D CRT for PTV and 0.03 ± 0.00 (RA, 0.05 ± 0.01 (HT, 0.03 ± 0.01 (SW IMRT and 3D CRT for CTV-P. Mean dose to bladder were 23.68 ± 13.23 Gy (RA, 24.55 ± 12.51 Gy (HT, 19.82 ± 11.61 Gy (IMRT and 23.56 ± 12.81 Gy (3D CRT, whereas mean dose to rectum was 36.85 ± 12.92 Gy (RA, 33.18 ± 11.12 Gy (HT, IMRT and 38.67 ± 12.84 Gy (3D CRT. Conclusion: All studied intensity-modulated techniques yield treatment plans of significantly improved quality when compared with 3D CRT, with HT providing best organs at risk sparing and RA being the most efficient treatment option, reducing treatment time to 1.45-3.7 min and monitor unit to <400 for a 2 Gy fraction.

  9. High voltage dc-dc converter with dynamic voltage regulation and decoupling during load-generated arcs

    Science.gov (United States)

    Shimer, Daniel W.; Lange, Arnold C.

    1995-01-01

    A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules.

  10. A hybrid conformal planning technique with solitary dynamic portal for postmastectomy radiotherapy with regional nodes

    Directory of Open Access Journals (Sweden)

    K Mohamathu Rafic

    2017-01-01

    Full Text Available Purpose: This study focuses on incorporation of a solitary dynamic portal (SDP in conformal planning for postmastectomy radiotherapy (PMRT with nodal regions with an intention to overcome the treatment planning limitations imposed by conventional techniques. Materials and Methods: Twenty-four patients who underwent surgical mastectomy followed by PMRT were included in this study. Initially, a treatment plan comprising tangential beams fitted to beam's-eye-view (BEV of chest wall (CW and a direct anterior field fitted to BEV of nodal region, both sharing a single isocenter was generated using Eclipse treatment planning system. Multiple field-in-fields with optimum beam weights (5% per field were added primarily from the medial tangent, fitted to BEV of entire target volume, and finally converted into a dynamic portal. Dosimetric analysis for the treatment plans and fluence verification for the dynamic portals were performed. Results and Discussion: Conformal plans with SDP showed excellent dose coverage (V95%>95%, higher degree of tumor dose conformity (≤1.25 and homogeneity (≤0.12 without compromising the organ at risk sparing for PMRT with nodal region. Treatment plans with SDP considerably reduced the lower isodose spread to the ipsilateral lung, heart, and healthy tissue without affecting the dose homogeneity. Further, gamma evaluation showed more than 96% pixel pass rate for standard 3%/3 mm dose difference and distance-to-agreement criteria. Moreover, this plan offers less probability of “geometrical miss” at the highly irregular CW with regional nodal radiotherapy. Conclusion: Hybrid conformal plans with SDP would facilitate improved dose distribution and reduced uncertainty in delivery and promises to be a suitable treatment option for complex postmastectomy CW with regional nodal irradiation.

  11. Single-molecule conformational dynamics of a biologically functional hydroxocobalamin riboswitch.

    Science.gov (United States)

    Holmstrom, Erik D; Polaski, Jacob T; Batey, Robert T; Nesbitt, David J

    2014-12-03

    Riboswitches represent a family of highly structured regulatory elements found primarily in the leader sequences of bacterial mRNAs. They function as molecular switches capable of altering gene expression; commonly, this occurs via a conformational change in a regulatory element of a riboswitch that results from ligand binding in the aptamer domain. Numerous studies have investigated the ligand binding process, but little is known about the structural changes in the regulatory element. A mechanistic description of both processes is essential for deeply understanding how riboswitches modulate gene expression. This task is greatly facilitated by studying all aspects of riboswitch structure/dynamics/function in the same model system. To this end, single-molecule fluorescence resonance energy transfer (smFRET) techniques have been used to directly observe the conformational dynamics of a hydroxocobalamin (HyCbl) binding riboswitch (env8HyCbl) with a known crystallographic structure.1 The single-molecule RNA construct studied in this work is unique in that it contains all of the structural elements both necessary and sufficient for regulation of gene expression in a biological context. The results of this investigation reveal that the undocking rate constant associated with the disruption of a long-range kissing-loop (KL) interaction is substantially decreased when the ligand is bound to the RNA, resulting in a preferential stabilization of the docked conformation. Notably, the formation of this tertiary KL interaction directly sequesters the Shine-Dalgarno sequence (i.e., the ribosome binding site) via base-pairing, thus preventing translation initiation. These results reveal that the conformational dynamics of this regulatory switch are quantitatively described by a four-state kinetic model, whereby ligand binding promotes formation of the KL interaction. The results of complementary cell-based gene expression experiments conducted in Escherichia coli are highly

  12. Elucidating molecular motion through structural and dynamic filters of energy-minimized conformer ensembles.

    Science.gov (United States)

    Emani, Prashant S; Bardaro, Michael F; Huang, Wei; Aragon, Sergio; Varani, Gabriele; Drobny, Gary P

    2014-02-20

    Complex RNA structures are constructed from helical segments connected by flexible loops that move spontaneously and in response to binding of small molecule ligands and proteins. Understanding the conformational variability of RNA requires the characterization of the coupled time evolution of interconnected flexible domains. To elucidate the collective molecular motions and explore the conformational landscape of the HIV-1 TAR RNA, we describe a new methodology that utilizes energy-minimized structures generated by the program "Fragment Assembly of RNA with Full-Atom Refinement (FARFAR)". We apply structural filters in the form of experimental residual dipolar couplings (RDCs) to select a subset of discrete energy-minimized conformers and carry out principal component analyses (PCA) to corroborate the choice of the filtered subset. We use this subset of structures to calculate solution T1 and T(1ρ) relaxation times for (13)C spins in multiple residues in different domains of the molecule using two simulation protocols that we previously published. We match the experimental T1 times to within 2% and the T(1ρ) times to within less than 10% for helical residues. These results introduce a protocol to construct viable dynamic trajectories for RNA molecules that accord well with experimental NMR data and support the notion that the motions of the helical portions of this small RNA can be described by a relatively small number of discrete conformations exchanging over time scales longer than 1 μs.

  13. Volumetric Modulation Arc Radiotherapy With Flattening Filter-Free Beams Compared With Static Gantry IMRT and 3D Conformal Radiotherapy for Advanced Esophageal Cancer: A Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Nicolini, Giorgia, E-mail: giorgia.nicolini@eoc.ch [Oncology Institute of Southern Switzerland, Medical Physics Unit, Bellinzona (Switzerland); Ghosh-Laskar, Sarbani; Shrivastava, Shyam Kishore; Banerjee, Sushovan; Chaudhary, Suresh; Agarwal, Jai Prakash; Munshi, Anusheel [Tata Memorial Hospital, Mumbai (India); Clivio, Alessandro; Fogliata, Antonella [Oncology Institute of Southern Switzerland, Medical Physics Unit, Bellinzona (Switzerland); Mancosu, Pietro [Department of Radiation Oncology, Istituto Clinico Humanitas, Milano-Rozzano (Italy); Vanetti, Eugenio; Cozzi, Luca [Oncology Institute of Southern Switzerland, Medical Physics Unit, Bellinzona (Switzerland)

    2012-10-01

    Purpose: A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving {>=}95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving {>=}5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. Results: RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 {+-} 0.1 for RA and IMRT and 1.5 {+-} 0.2 for 3D-CRT. The mean lung dose was 12.2 {+-} 4.5 for IMRT, 11.3 {+-} 4.6 for RA, and 10.8 {+-} 4.4 for RA with FFF beams, 18.2 {+-} 8.5 for 3D-CRT. The percentage of volume receiving {>=}20 Gy ranged from 23.6% {+-} 9.1% to 21.1% {+-} 9.7% for IMRT and RA (FFF beams) and 39.2% {+-} 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 {+-} 139, 322 {+-} 20, and 387 {+-} 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a {approx}20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different

  14. Dosimetric properties of an amorphous-silicon EPID used in continuous acquisition mode for application to dynamic and arc IMRT.

    Science.gov (United States)

    McCurdy, B M C; Greer, P B

    2009-07-01

    Dosimetric properties of an amorphous-silicon electronic portal imaging device (EPID) operated in a real-time acquisition mode were investigated. This mode will be essential for time-resolved dose verification of dynamic (sliding window) intensity modulated radiation therapy (IMRT) and intensity modulated arc radiation therapy (arc-IMRT). The EPID was used in continuous acquisition mode (i.e., "cine" mode) where individual sequential image frames are acquired in real time. The properties studied include dose linearity, reproducibility of response, and image stability. Results of using the continuous acquisition mode with several example treatments including dynamic IMRT, arc treatment, and single-arc-IMRT are compared to results using the well-studied integrated acquisition mode (i.e., "frame averaging" or "IMRT" mode). Real-time EPID response was also compared to real-time ion-chamber data for selected points in the deliveries. The example treatment deliveries in both continuous and integrated acquisition modes were converted to arbitrary EPID dose units via a calibration field. The summation of all acquired continuous mode images was compared using percentage dose difference to the single image acquired in the integrated mode using in-field pixels only (defined as those pixels > 10% of maximum, in-field signal). Using the continuous acquisition mode, the EPID response was not linear with dose. It was found that the continuous mode dose response corresponded approximately to dropping one image per acquisition session. Reproducibility of EPID response to low monitor units (MUs) was found to be poor but greatly improved with increasing MU. Open field profiles were found to be stable in the cross-plane direction but required several frames to become stable in the in-plane direction. However, both of these issues are clinically insignificant due to arc-IMRT deliveries requiring relatively large monitor units (> 100 MU). Analysis of the five IMRT, arc, and arc

  15. Enhanced conformational sampling of nucleic acids by a new Hamiltonian replica exchange molecular dynamics approach.

    Science.gov (United States)

    Curuksu, Jeremy; Zacharias, Martin

    2009-03-14

    Although molecular dynamics (MD) simulations have been applied frequently to study flexible molecules, the sampling of conformational states separated by barriers is limited due to currently possible simulation time scales. Replica-exchange (Rex)MD simulations that allow for exchanges between simulations performed at different temperatures (T-RexMD) can achieve improved conformational sampling. However, in the case of T-RexMD the computational demand grows rapidly with system size. A Hamiltonian RexMD method that specifically enhances coupled dihedral angle transitions has been developed. The method employs added biasing potentials as replica parameters that destabilize available dihedral substates and was applied to study coupled dihedral transitions in nucleic acid molecules. The biasing potentials can be either fixed at the beginning of the simulation or optimized during an equilibration phase. The method was extensively tested and compared to conventional MD simulations and T-RexMD simulations on an adenine dinucleotide system and on a DNA abasic site. The biasing potential RexMD method showed improved sampling of conformational substates compared to conventional MD simulations similar to T-RexMD simulations but at a fraction of the computational demand. It is well suited to study systematically the fine structure and dynamics of large nucleic acids under realistic conditions including explicit solvent and ions and can be easily extended to other types of molecules.

  16. Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.

    Science.gov (United States)

    LeMaster, David M; Hernandez, Griselda

    2015-01-01

    Among the 22 FKBP domains in the human genome, FKBP12.6 and the first FKBP domains (FK1) of FKBP51 and FKBP52 are evolutionarily and structurally most similar to the archetypical FKBP12. As such, the development of inhibitors with selectivity among these four FKBP domains poses a significant challenge for structure-based design. The pleiotropic effects of these FKBP domains in a range of signaling processes such as the regulation of ryanodine receptor calcium channels by FKBP12 and FKBP12.6 and steroid receptor regulation by the FK1 domains of FKBP51 and FKBP52 amply justify the efforts to develop selective therapies. In contrast to their close structural similarities, these four FKBP domains exhibit a substantial diversity in their conformational flexibility. A number of distinct conformational transitions have been characterized for FKBP12 spanning timeframes from 20 s to 10 ns and in each case these dynamics have been shown to markedly differ from the conformational behavior for one or more of the other three FKBP domains. Protein flexibilitybased inhibitor design could draw upon the transitions that are significantly populated in only one of the targeted proteins. Both the similarities and differences among these four proteins valuably inform the understanding of how dynamical effects propagate across the FKBP domains as well as potentially how such intramolecular transitions might couple to the larger scale transitions that are central to the signaling complexes in which these FKBP domains function.

  17. Conformational dynamics of stem II of the U2 snRNA.

    Science.gov (United States)

    Rodgers, Margaret L; Tretbar, U Sandy; Dehaven, Alexander; Alwan, Amir A; Luo, George; Mast, Hannah M; Hoskins, Aaron A

    2016-02-01

    The spliceosome undergoes dramatic changes in both small nuclear RNA (snRNA) composition and structure during assembly and pre-mRNA splicing. It has been previously proposed that the U2 snRNA adopts two conformations within the stem II region: stem IIa or stem IIc. Dynamic rearrangement of stem IIa into IIc and vice versa is necessary for proper progression of the spliceosome through assembly and catalysis. How this conformational transition is regulated is unclear; although, proteins such as Cus2p and the helicase Prp5p have been implicated in this process. We have used single-molecule Förster resonance energy transfer (smFRET) to study U2 stem II toggling between stem IIa and IIc. Structural interconversion of the RNA was spontaneous and did not require the presence of a helicase; however, both Mg(2+) and Cus2p promote formation of stem IIa. Destabilization of stem IIa by a G53A mutation in the RNA promotes stem IIc formation and inhibits conformational switching of the RNA by both Mg(2+) and Cus2p. Transitioning to stem IIa can be restored using Cus2p mutations that suppress G53A phenotypes in vivo. We propose that during spliceosome assembly, Cus2p and Mg(2+) may work together to promote stem IIa formation. During catalysis the spliceosome could then toggle stem II with the aid of Mg(2+) or with the use of functionally equivalent protein interactions. As noted in previous studies, the Mg(2+) toggling we observe parallels previous observations of U2/U6 and Prp8p RNase H domain Mg(2+)-dependent conformational changes. Together these data suggest that multiple components of the spliceosome may have evolved to switch between conformations corresponding to open or closed active sites with the aid of metal and protein cofactors. © 2016 Rodgers et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  18. On dynamical realizations of l-conformal Galilei and Newton-Hooke algebras

    CERN Document Server

    Galajinsky, Anton

    2015-01-01

    In two recent papers [N. Aizawa, Y. Kimura, J. Segar, J. Phys. A 46 (2013) 405204] and [N. Aizawa, Z. Kuznetsova, F. Toppan, J. Math. Phys. 56 (2015) 031701], representation theory of the centrally extended l-conformal Galilei algebra has been applied so as to construct second order differential equations exhibiting the l-conformal Galilei group as kinematical symmetry. It was suggested to treat them as the Schrodinger equations which involve Hamiltonians describing dynamical systems without higher derivatives. The Hamiltonians possess two unusual features, however. First, they involve the standard kinetic term only for one degree of freedom, while the remaining variables provide contributions linear in momenta. This is typical for Ostrogradski's canonical approach to the description of higher derivative systems. Second, the Hamiltonian in the second paper is not Hermitian in the conventional sense. In this work, we study the classical limit of the quantum Hamiltonians and demonstrate that the first of them i...

  19. Conformational Solvation Studies of LIGNOLs with Molecular Dynamics and Conductor-Like Screening Model

    Directory of Open Access Journals (Sweden)

    Thomas Sandberg

    2012-08-01

    Full Text Available Molecular dynamics (MD simulations were performed on sterically hindered -conidendrin-based chiral 1,4-diols (LIGNOLs from the naturally occurring lignan hydroxymatairesinol (HMR using the GROMACS software. The aim of this study was to explore the conformational behaviour of the LIGNOLs in aqueous solution adopting the TIP4P model. The topologies of the LIGNOLs were constructed manually and they were modeled with the OPLS-AA force field implemented in GROMACS. The four most relevant torsional angles in the LIGNOLs were properly analyzed during the simulations. The determining property for the conformation preferred in aqueous solution was found to be the lowest energy in gas phase. The solvation effects on the LIGNOLs were also studied by quantum chemical calculations applying the COnductor-like Screening MOdel (COSMO. The hydration studies of the MD simulations showed that several of these LIGNOLs, produced from a renewable source, have a great potential of acting as chiral catalysts.

  20. Fast 3D Pattern Synthesis with Polarization and Dynamic Range Ratio Control for Conformal Antenna Arrays

    Directory of Open Access Journals (Sweden)

    Massimiliano Comisso

    2014-01-01

    Full Text Available This paper proposes an iterative algorithm for the 3D synthesis of the electric far-field pattern of a conformal antenna array in the presence of requirements on both the polarization and the dynamic range ratio (DRR of the excitations. Thanks to the use of selectable weights, the algorithm allows a versatile control of the DRR and of the polarization in a given angular region and requires a low CPU time to provide the array excitations. Furthermore, a modified version of the algorithm is developed to enable the optimization of the polarization state by phase-only control. Numerical results are presented to verify the usefulness of the proposed approach for the joint pattern and polarization synthesis of conformal arrays with reduced or even unitary DRR.

  1. Conformational dynamics of dry lamellar crystals of sugar based lipids: an atomistic simulation study.

    Directory of Open Access Journals (Sweden)

    Vijayan ManickamAchari

    Full Text Available The rational design of a glycolipid application (e.g. drug delivery with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside and a C12C10 branched β-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (∼20% in the hydrophobic region of the lamellar crystal (LC phase. In contrast, the branched chain glycolipid in the fluid Lα phase has a high gauche population of up to ∼40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11-15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.

  2. DNA Conformational Variations Induced by Stretching 3'5'-Termini Studied by Molecular Dynamics Simulations

    Institute of Scientific and Technical Information of China (English)

    QI Wen-Peng; LEI Xiao-Ling

    2011-01-01

    @@ Investigating the interaction between protein and stretched DNA molecules has become a new way to study the protein DNA interaction.The conformations from different stretching methods give us a further understanding of the interaction between protein and DNA.We study the conformational variations of a 22-mer DNA caused by stretching both 3'-and 5'-termini by molecular dynamics simulations.It requires 250kJ/mol to stretch the DNA molecule by 3'5'-termini for 3.5 run and the force plateau is at 123.8 pN.The stretching 3'5'-termini leads to large values of the angle opening and the dihedral propeller between bases in one base pair, the double helix untwists from 34°to 20°and the successive base pairs rolls to the side of the DNA major groove.The distances between successive base pairs increases from 3.2.(A) to 5.6(A).%Investigating the interaction between protein and stretched DNA molecules has become a new way to study the protein DNA interaction. The conformations from different stretching methods give us a further understanding of the interaction between protein and DNA. We study the conformational variations of a 22-met DNA caused by stretching both 3'- and 5'-termini by molecular dynamics simulations. It requires 250k J/mol to stretch the DNA molecule by 3'5'-termini for 3.5nm and the force plateau is at 123.8pN. The stretching 3'5'-termini leads to large values of the angle opening and the dihedral propeller between bases in one base pair, the double helix untwists from 34° to 20° and the successive base pairs rolls to the side of the DNA major groove. The distances between successive base pairs increases from 3.2 (A) to 5.6 (A).

  3. Accelerated molecular dynamics and protein conformational change: a theoretical and practical guide using a membrane embedded model neurotransmitter transporter.

    Science.gov (United States)

    Gedeon, Patrick C; Thomas, James R; Madura, Jeffry D

    2015-01-01

    Molecular dynamics simulation provides a powerful and accurate method to model protein conformational change, yet timescale limitations often prevent direct assessment of the kinetic properties of interest. A large number of molecular dynamic steps are necessary for rare events to occur, which allow a system to overcome energy barriers and conformationally transition from one potential energy minimum to another. For many proteins, the energy landscape is further complicated by a multitude of potential energy wells, each separated by high free-energy barriers and each potentially representative of a functionally important protein conformation. To overcome these obstacles, accelerated molecular dynamics utilizes a robust bias potential function to simulate the transition between different potential energy minima. This straightforward approach more efficiently samples conformational space in comparison to classical molecular dynamics simulation, does not require advanced knowledge of the potential energy landscape and converges to the proper canonical distribution. Here, we review the theory behind accelerated molecular dynamics and discuss the approach in the context of modeling protein conformational change. As a practical example, we provide a detailed, step-by-step explanation of how to perform an accelerated molecular dynamics simulation using a model neurotransmitter transporter embedded in a lipid cell membrane. Changes in protein conformation of relevance to the substrate transport cycle are then examined using principle component analysis.

  4. Modeling Arcs

    CERN Document Server

    Insepov, Zeke; Veitzer, Seth; Mahalingam, Sudhakar

    2011-01-01

    Although vacuum arcs were first identified over 110 years ago, they are not yet well understood. We have since developed a model of breakdown and gradient limits that tries to explain, in a self-consistent way: arc triggering, plasma initiation, plasma evolution, surface damage and gra- dient limits. We use simple PIC codes for modeling plasmas, molecular dynamics for modeling surface breakdown, and surface damage, and mesoscale surface thermodynamics and finite element electrostatic codes for to evaluate surface properties. Since any given experiment seems to have more variables than data points, we have tried to consider a wide variety of arcing (rf structures, e beam welding, laser ablation, etc.) to help constrain the problem, and concentrate on common mechanisms. While the mechanisms can be comparatively simple, modeling can be challenging.

  5. New perspectives on the dynamics of AC and DC plasma arcs exposed to cross-fields

    Science.gov (United States)

    Abdo, Youssef; Rohani, Vandad; Cauneau, François; Fulcheri, Laurent

    2017-02-01

    Interactions between an arc and external fields are crucially important for the design and the optimization of modern plasma torches. Multiple studies have been conducted to help better understand the behavior of DC and AC current arcs exposed to external and ‘self-induced’ magnetic fields, but the theoretical foundations remain very poorly explored. An analytical investigation has therefore been carried out in order to study the general behavior of DC and AC arcs under the effect of random cross-fields. A simple differential equation describing the general behavior of a planar DC or AC arc has been obtained. Several dimensionless numbers that depend primarily on arc and field parameters and the main arc characteristics (temperature, electric field strength) have also been determined. Their magnitude indicates the general tendency pattern of the arc evolution. The analytical results for many case studies have been validated using an MHD numerical model. The main purpose of this investigation was deriving a practical analytical model for the electric arc, rendering possible its stabilization and control, and the enhancement of the plasma torch power.

  6. Dynamic fluctuations provide the basis of a conformational switch mechanism in apo cyclic AMP receptor protein.

    Directory of Open Access Journals (Sweden)

    Burcu Aykaç Fas

    Full Text Available Escherichia coli cyclic AMP Receptor Protein (CRP undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD simulations and Gaussian Network Model (GNM. The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra- and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.

  7. Global Conformational Dynamics of HIV-1 Reverse Transcriptase Bound to Non-Nucleoside Inhibitors

    Directory of Open Access Journals (Sweden)

    Peter V. Coveney

    2012-07-01

    Full Text Available HIV-1 Reverse Transcriptase (RT is a multifunctional enzyme responsible for the transcription of the RNA genome of the HIV virus into DNA suitable for incorporation within the DNA of human host cells. Its crucial role in the viral life cycle has made it one of the major targets for antiretroviral drug therapy. The Non-Nucleoside RT Inhibitor (NNRTI class of drugs binds allosterically to the enzyme, affecting many aspects of its activity. We use both coarse grained network models and atomistic molecular dynamics to explore the changes in protein dynamics induced by NNRTI binding. We identify changes in the flexibility and conformation of residue Glu396 in the RNaseH primer grip which could provide an explanation for the acceleration in RNaseH cleavage rate observed experimentally in NNRTI bound HIV-1 RT. We further suggest a plausible path for conformational and dynamic changes to be communicated from the vicinity of the NNRTI binding pocket to the RNaseH at the other end of the enzyme.

  8. Conformational dynamics of a protein in the folded and the unfolded state

    Energy Technology Data Exchange (ETDEWEB)

    Fitter, Joerg

    2003-08-01

    In a quasielastic neutron scattering experiment, the picosecond dynamics of {alpha}-amylase was investigated for the folded and the unfolded state of the protein. In order to ensure a reasonable interpretation of the internal protein dynamics, the protein was measured in D{sub 2}O-buffer solution. The much higher structural flexibility of the pH induced unfolded state as compared to the native folded state was quantified using a simple analytical model, describing a local diffusion inside a sphere. In terms of this model the conformational volume, which is explored mainly by confined protein side-chain movements, is parameterized by the radius of a sphere (folded state, r=1.2 A; unfolded state, 1.8 A). Differences in conformational dynamics between the folded and the unfolded state of a protein are of fundamental interest in the field of protein science, because they are assumed to play an important role for the thermodynamics of folding/unfolding transition and for protein stability.

  9. Collective Dynamics of Belief Evolution under Cognitive Coherence and Social Conformity

    Science.gov (United States)

    Rodriguez, Nathaniel; Bollen, Johan

    2016-01-01

    Human history has been marked by social instability and conflict, often driven by the irreconcilability of opposing sets of beliefs, ideologies, and religious dogmas. The dynamics of belief systems has been studied mainly from two distinct perspectives, namely how cognitive biases lead to individual belief rigidity and how social influence leads to social conformity. Here we propose a unifying framework that connects cognitive and social forces together in order to study the dynamics of societal belief evolution. Each individual is endowed with a network of interacting beliefs that evolves through interaction with other individuals in a social network. The adoption of beliefs is affected by both internal coherence and social conformity. Our framework may offer explanations for how social transitions can arise in otherwise homogeneous populations, how small numbers of zealots with highly coherent beliefs can overturn societal consensus, and how belief rigidity protects fringe groups and cults against invasion from mainstream beliefs, allowing them to persist and even thrive in larger societies. Our results suggest that strong consensus may be insufficient to guarantee social stability, that the cognitive coherence of belief-systems is vital in determining their ability to spread, and that coherent belief-systems may pose a serious problem for resolving social polarization, due to their ability to prevent consensus even under high levels of social exposure. We argue that the inclusion of cognitive factors into a social model could provide a more complete picture of collective human dynamics. PMID:27812210

  10. Effects of carbon nanofiller characteristics on PTT chain conformation and dynamics: A computational study

    Science.gov (United States)

    Asadinezhad, Ahmad; Kelich, Payam

    2017-01-01

    The effects of nanofiller chemistry and geometry on static and dynamic properties of an aromatic polyester, poly (trimethylene terephthalate), were addressed thanks to long-run classical molecular dynamics simulation. Two carbon nanofillers, graphene and carbon nanotube, were employed, where graphene was used in pristine and functionalized forms and carbon nanotube was used in two different diameters. The nanofiller geometry and chemistry were found to exert significant effects on conformation and dynamic behavior of PTT chain at the interface within the time scale the simulation was performed. It was found that PTT chain underwent interaction of van der Waals type with nanofiller via two subsequent phases, adsorption and orientation. The former stage, with definite characteristic time, involved translation of polymer chain toward interface while the latter was controlled by vibrational motions of chain atoms. The consequence of interaction was an increase in conformational order of polymer chain by transition to folded shape being favorable for any subsequent structural ordering (crystallization). The interaction of polymer with nanofiller gave rise to a reduction in overall mobility of polymer chain characterized by crossover from normal diffusive motion to subdiffusive mode.

  11. Structural Dynamics and Conformational Equilibria of SERCA Regulatory Proteins in Membranes by Solid-State NMR Restrained Simulations

    Science.gov (United States)

    De Simone, Alfonso; Mote, Kaustubh R.; Veglia, Gianluigi

    2014-01-01

    Solid-state NMR spectroscopy is emerging as a powerful approach to determine structure, topology, and conformational dynamics of membrane proteins at the atomic level. Conformational dynamics are often inferred and quantified from the motional averaging of the NMR parameters. However, the nature of these motions is difficult to envision based only on spectroscopic data. Here, we utilized restrained molecular dynamics simulations to probe the structural dynamics, topology and conformational transitions of regulatory membrane proteins of the calcium ATPase SERCA, namely sarcolipin and phospholamban, in explicit lipid bilayers. Specifically, we employed oriented solid-state NMR data, such as dipolar couplings and chemical shift anisotropy measured in lipid bicelles, to refine the conformational ensemble of these proteins in lipid membranes. The samplings accurately reproduced the orientations of transmembrane helices and showed a significant degree of convergence with all of the NMR parameters. Unlike the unrestrained simulations, the resulting sarcolipin structures are in agreement with distances and angles for hydrogen bonds in ideal helices. In the case of phospholamban, the restrained ensemble sampled the conformational interconversion between T (helical) and R (unfolded) states for the cytoplasmic region that could not be observed using standard structural refinements with the same experimental data set. This study underscores the importance of implementing NMR data in molecular dynamics protocols to better describe the conformational landscapes of membrane proteins embedded in realistic lipid membranes. PMID:24940774

  12. Hadron spectroscopy and dynamics from light-front holography and conformal symmetry

    Directory of Open Access Journals (Sweden)

    de Téramond Guy F.

    2014-06-01

    Full Text Available To a first semiclassical approximation one can reduce the multi-parton light-front problem in QCD to an effective one-dimensional quantum field theory, which encodes the fundamental conformal symmetry of the classical QCD Lagrangian. This procedure leads to a relativistic light-front wave equation for arbitrary spin which incorporates essential spectroscopic and non-perturbative dynamical features of hadron physics. The mass scale for confinement and higher dimensional holographic mapping to AdS space are also emergent properties of this framework.

  13. Volumetric intensity-modulated arc therapy vs. 3-dimensional conformal radiotherapy for primary chemoradiotherapy of anal carcinoma. Effects on treatment-related side effects and survival

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Hanne Elisabeth; Droege, Leif Hendrik; Hennies, Steffen; Herrmann, Markus Karl; Wolff, Hendrik Andreas [University Medical Center Goettingen, Dept. of Radiotherapy and Radiooncology, Goettingen (Germany); Gaedcke, Jochen [University Medical Center Goettingen, Dept. of General Surgery, Goettingen (Germany)

    2015-11-15

    Primary chemoradiotherapy (CRT) is the standard treatment for locally advanced anal carcinoma. This study compared volumetric intensity-modulated arc therapy (VMAT) to 3-dimensional conformal radiotherapy (3DCRT) in terms of treatment-related side effects and survival. From 1992-2014, 103 consecutive patients with anal carcinoma UICC stage I-III were treated. Concomitant CRT consisted of whole pelvic irradiation, including the iliac and inguinal lymph nodes, with 50.4 Gy (1.8 Gy per fractions) by VMAT (n = 17) or 3DCRT (n = 86) as well as two cycles of 5-fluorouracil and mitomycin C. Acute organ and hematological toxicity were assessed according to the Common Terminology Criteria (CTC) for Adverse Events version 3.0. Side effects ≥ grade 3 were scored as high-grade toxicity. High-grade acute organ toxicity CTC ≥ 3 (P < 0.05), especially proctitis (P = 0.03), was significantly reduced in VMAT patients. The 2-year locoregional control (LRC) and disease-free survival (DFS) were both 100 % for VMAT patients compared with 80 and 73 % for 3DCRT patients. VMAT was shown to be a feasible technique, achieving significantly lower rates of acute organ toxicity and promising results for LRC and DFS. Future investigations will aim at assessing the advantages of VMAT with respect to late toxicity and survival after a prolonged follow-up time. (orig.) [German] Die primaere Radiochemotherapie (RCT) gilt als Standardtherapie fuer lokal fortgeschrittene Analkarzinome. In dieser Studie wurde die volumetrisch modulierte Rotationstherapie (''volumetric intensity-modulated arc therapy'', VMAT) mit der klassischen dreidimensionalen konformalen Radiotherapie (3DCRT) hinsichtlich therapieassoziierter Nebenwirkungen und Ueberleben verglichen. Von 1992-2014 wurden 103 aufeinanderfolgende Patienten mit einem Analkarzinom im UICC-Stadium I-III behandelt. Die kombinierte RCT bestand aus der Bestrahlung des gesamten Beckens inklusive der iliakalen und der inguinalen

  14. Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma. A dosimetric comparison

    Energy Technology Data Exchange (ETDEWEB)

    Adeberg, S.; Debus, J. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Harrabi, S.B.; Bougatf, N.; Rieber, J.; Koerber, S.A.; Herfarth, K.; Rieken, S. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Bernhardt, D.; Syed, M.; Sprave, T.; Mohr, A. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Abdollahi, A. [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Haberer, T. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Combs, S.E. [Technische Universitaet Muenchen, Department of Radiation Oncology, Muenchen (Germany); Helmholtz Zentrum Muenchen, Institut fuer Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Neuherberg (Germany)

    2016-11-15

    The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment. We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated. Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (-20.2 %, -22.7 %); supratentorial (-14.2 %, -20,8 %) and infratentorial (-91.0 %, -77.0 %) regions; brainstem (-67.6 %, -28.1 %); pituitary gland (-52.9 %, -52.5 %); contralateral hippocampus (-98.9 %, -98.7 %); and contralateral subventricular zone (-62.7 %, -66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities. Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG. (orig.) [German] Die Prognose bei ''High-grade''-Gliomen (HGG) ist infaust. Gerade bei diesen Patienten sollten therapieassoziierte Nebenwirkungen minimiert werden

  15. Dynamic Conformations of Nucleosome Arrays in Solution from Small-Angle X-ray Scattering

    Science.gov (United States)

    Howell, Steven C.

    Chromatin conformation and dynamics remains unsolved despite the critical role of the chromatin in fundamental genetic functions such as transcription, replication, and repair. At the molecular level, chromatin can be viewed as a linear array of nucleosomes, each consisting of 147 base pairs (bp) of double-stranded DNA (dsDNA) wrapped around a protein core and connected by 10 to 90 bp of linker dsDNA. Using small-angle X-ray scattering (SAXS), we investigated how the conformations of model nucleosome arrays in solution are modulated by ionic condition as well as the effect of linker histone proteins. To facilitate ensemble modeling of these SAXS measurements, we developed a simulation method that treats coarse-grained DNA as a Markov chain, then explores possible DNA conformations using Metropolis Monte Carlo (MC) sampling. This algorithm extends the functionality of SASSIE, a program used to model intrinsically disordered biological molecules, adding to the previous methods for simulating protein, carbohydrates, and single-stranded DNA. Our SAXS measurements of various nucleosome arrays together with the MC generated models provide valuable solution structure information identifying specific differences from the structure of crystallized arrays.

  16. Conformity, anticonformity and polarization of opinions: insights from a mathematical model of opinion dynamics

    CERN Document Server

    Krüger, Tyll; Weron, Tomasz

    2016-01-01

    Understanding and quantifying polarization in social systems is important because of many reasons. It could for instance help to avoid segregation and conflicts in the society (DiMaggio et al. 1996) or to control polarized debates and predict their outcomes (Walton 1991). In a recent paper (Siedlecki et al. 2016) we used an agent-based model of a segmented society to check if the polarization may be induced by a competition between conformity and anticonformity. Among other things we have shown that the interplay of intra-clique conformity and inter-clique anticonformity may indeed lead to a bi-polarized state of the system. This paper is a continuation of the work done in (Siedlecki et al. 2016). We consider here a slightly modified version of the model that allows for mathematical treatment and gives more insight into the dynamics of the system. We determine conditions needed to arrive at consensus in a double-clique network with conformity and anticonformity as types of social influence and find regimes, i...

  17. Ligand-Induced Conformational Changes and Conformational Dynamics in the Solution Structure of the Lactose Repressor Protein

    Science.gov (United States)

    Taraban, Marc; Zhan, Hongli; Whitten, Andrew E.; Langley, David B.; Matthews, Kathleen S.; Swint-Kruse, Liskin; Trewhella, Jill

    2008-01-01

    SUMMARY We present here the results of a series of small-angle X-ray scattering studies aimed at understanding the role of conformational changes and structural flexibility in DNA binding and allosteric signaling in a bacterial transcription regulator, Lactose repressor protein (LacI). Experiments were designed to detect possible conformational changes that occur when LacI binds either DNA or the inducer IPTG, or both. Our studies included the native LacI dimer of homodimers and a dimeric variant (R3), enabling us to probe conformational changes within the homodimers and distinguish them from those involving changes in the homodimer-homodimer relationships. The scattering data indicate that removal of operator DNA (oDNA) from R3 results in an unfolding and extension of the hinge-helix that connects the LacI regulatory and DNA-binding domains. In contrast, only very subtle conformational changes occur in the R3 dimer-oDNA complex upon IPTG binding, indicative of small adjustments in the orientations of domains and/or sub-domains within the structure. The binding of IPTG to native (tetrameric) LacI-oDNA complexes also appears to facilitate a modest change in the average homodimer-homodimer disposition. Notably, the crystal structure of the native LacI-oDNA complex differs significantly from the average solution conformation. The solution scattering data are best-fit by an ensemble of structures that includes (1) ~60% of the V-shaped dimer-of-homodimers observed in the crystal structure, and (2) ~40% of molecules with more “open” forms, such as those generated when the homodimers move with respect to each other about the tetramerization domain. In gene regulation, such a flexible LacI would be beneficial for the interaction of its two DNA binding domains, positioned at the tips of the V, with the required two of three LacI operators needed for full repression. PMID:18164724

  18. NMR and molecular dynamics studies of the conformational epitope of the type III group B Streptococcus capsular polysaccharide and derivatives.

    Science.gov (United States)

    Brisson, J R; Uhrinova, S; Woods, R J; van der Zwan, M; Jarrell, H C; Paoletti, L C; Kasper, D L; Jennings, H J

    1997-03-18

    The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.

  19. Dynamic analysis, transformation, dissemination and applications of scientific multidimensional data in ArcGIS Platform

    Science.gov (United States)

    Shrestha, S. R.; Collow, T. W.; Rose, B.

    2016-12-01

    Scientific datasets are generated from various sources and platforms but they are typically produced either by earth observation systems or by modelling systems. These are widely used for monitoring, simulating, or analyzing measurements that are associated with physical, chemical, and biological phenomena over the ocean, atmosphere, or land. A significant subset of scientific datasets stores values directly as rasters or in a form that can be rasterized. This is where a value exists at every cell in a regular grid spanning the spatial extent of the dataset. Government agencies like NOAA, NASA, EPA, USGS produces large volumes of near real-time, forecast, and historical data that drives climatological and meteorological studies, and underpins operations ranging from weather prediction to sea ice loss. Modern science is computationally intensive because of the availability of an enormous amount of scientific data, the adoption of data-driven analysis, and the need to share these dataset and research results with the public. ArcGIS as a platform is sophisticated and capable of handling such complex domain. We'll discuss constructs and capabilities applicable to multidimensional gridded data that can be conceptualized as a multivariate space-time cube. Building on the concept of a two-dimensional raster, a typical multidimensional raster dataset could contain several "slices" within the same spatial extent. We will share a case from the NOAA Climate Forecast Systems Reanalysis (CFSR) multidimensional data as an example of how large collections of rasters can be efficiently organized and managed through a data model within a geodatabase called "Mosaic dataset" and dynamically transformed and analyzed using raster functions. A raster function is a lightweight, raster-valued transformation defined over a mixed set of raster and scalar input. That means, just like any tool, you can provide a raster function with input parameters. It enables dynamic processing of only the

  20. New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Hugo de Almeida

    Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

  1. Evaluation of volumetric modulated arc therapy for cranial radiosurgery using multiple noncoplanar arcs

    Energy Technology Data Exchange (ETDEWEB)

    Audet, Chantal; Poffenbarger, Brett A.; Chang, Pauling; Jackson, Paul S.; Lundahl, Robert E.; Ryu, Stephen I.; Ray, Gordon R. [Radiation Oncology Department, Palo Alto Medical Foundation, Palo Alto, California 94301 (United States); Neurosurgery Department, Palo Alto Medical Foundation, Palo Alto, California 94301 (United States); Radiation Oncology Department, Palo Alto Medical Foundation, Palo Alto, California 94301 (United States); Neurosurgery Department, Palo Alto Medical Foundation, Palo Alto, California 94301 (United States); Radiation Oncology Department, Palo Alto Medical Foundation, Palo Alto, California 94301 (United States)

    2011-11-15

    Purpose: To evaluate a commercial volumetric modulated arc therapy (VMAT), using multiple noncoplanar arcs, for linac-based cranial radiosurgery, as well as evaluate the combined accuracy of the VMAT dose calculations and delivery. Methods: Twelve patients with cranial lesions of variable size (0.1-29 cc) and two multiple metastases patients were planned (Eclipse RapidArc AAA algorithm, v8.6.15) using VMAT (1-6 noncoplanar arcs), dynamic conformal arc (DCA, {approx}4 arcs), and IMRT (nine static fields). All plans were evaluated according to a conformity index (CI), healthy brain tissue doses and volumes, and the dose to organs at risk. A 2D dose distribution was measured (Varian Novalis Tx, HD120 MLC, 1000 MU/min, 6 MV beam) for the {approx}4 arc VMAT treatment plans using calibrated film dosimetry. Results: The CI (0-1 best) average for all plans was best for {approx}4 noncoplanar arc VMAT at 0.86 compared with {approx}0.78 for IMRT and a single arc VMAT and 0.68 for DCA. The volumes of healthy brain receiving 50% of the prescribed target coverage dose or more (V{sub 50%}) were lowest for the four arc VMAT [RA(4)] and DCA plans. The average ratio of the V{sub 50%} for the other plans to the RA(4) V{sub 50%} were 1.9 for a single noncoplanar arc VMAT [RA(1nc)], 1.4 for single full coplanar arc VMAT [RA(1f)] and 1.3 for IMRT. The V{sub 50%} improved significantly for single isocenter multiple metastases plan when two noncoplanar VMAT arcs were added to a full single coplanar one. The maximum dose to 5 cc of the outer 1 cm rim of healthy brain which one may want to keep below nonconsequential doses of 300-400 cGy, was 2-3 times greater for IMRT, RA(1nc) and RA(1f) plans compared with the multiple noncoplanar arc DCA and RA(4) techniques. Organs at risk near (0-4 mm) to targets were best spared by (i) single noncoplanar arcs when the targets are lateral to the organ at risk and (ii) by skewed nonvertical planes of IMRT fields when the targets are not lateral to the

  2. Examining the conformational dynamics of membrane proteins in situ with site-directed fluorescence labeling.

    Science.gov (United States)

    Richards, Ryan; Dempski, Robert E

    2011-05-29

    Two electrode voltage clamp electrophysiology (TEVC) is a powerful tool to investigate the mechanism of ion transport1 for a wide variety of membrane proteins including ion channels, ion pumps, and transporters. Recent developments have combined site-specific fluorophore labeling alongside TEVC to concurrently examine the conformational dynamics at specific residues and function of these proteins on the surface of single cells. We will describe a method to study the conformational dynamics of membrane proteins by simultaneously monitoring fluorescence and current changes using voltage-clamp fluorometry. This approach can be used to examine the molecular motion of membrane proteins site-specifically following cysteine replacement and site-directed fluorophore labeling. Furthermore, this method provides an approach to determine distance constraints between specific residues. This is achieved by selectively attaching donor and acceptor fluorophores to two mutated cysteine residues of interest. In brief, these experiments are performed following functional expression of the desired protein on the surface of Xenopus leavis oocytes. The large surface area of these oocytes enables facile functional measurements and a robust fluorescence signal. It is also possible to readily change the extracellular conditions such as pH, ligand or cations/anions, which can provide further information on the mechanism of membrane proteins. Finally, recent developments have also enabled the manipulation of select internal ions following co-expression with a second protein. Our protocol is described in multiple parts. First, cysteine scanning mutagenesis proceeded by fluorophore labeling is completed at residues located at the interface of the transmembrane and extracellular domains. Subsequent experiments are designed to identify residues which demonstrate large changes in fluorescence intensity (<5%) upon a conformational change of the protein. Second, these changes in fluorescence

  3. Mapping the conformational dynamics and pathways of spontaneous steric zipper Peptide oligomerization.

    Directory of Open Access Journals (Sweden)

    Dirk Matthes

    Full Text Available The process of protein misfolding and self-assembly into various, polymorphic aggregates is associated with a number of important neurodegenerative diseases. Only recently, crystal structures of several short peptides have provided detailed structural insights into -sheet rich aggregates, known as amyloid fibrils. Knowledge about early events of the formation and interconversion of small oligomeric states, an inevitable step in the cascade of peptide self-assembly, however, remains still limited. We employ molecular dynamics simulations in explicit solvent to study the spontaneous aggregation process of steric zipper peptide segments from the tau protein and insulin in atomistic detail. Starting from separated chains with random conformations, we find a rapid formation of structurally heterogeneous, -sheet rich oligomers, emerging from multiple bimolecular association steps and diverse assembly pathways. Furthermore, our study provides evidence that aggregate intermediates as small as dimers can be kinetically trapped and thus affect the structural evolution of larger oligomers. Alternative aggregate structures are found for both peptide sequences in the different independent simulations, some of which feature characteristics of the known steric zipper conformation (e.g., -sheet bilayers with a dry interface. The final aggregates interconvert with topologically distinct oligomeric states exclusively via internal rearrangements. The peptide oligomerization was analyzed through the perspective of a minimal oligomer, i.e., the dimer. Thereby all observed multimeric aggregates can be consistently mapped onto a space of reduced dimensionality. This novel method of conformational mapping reveals heterogeneous association and reorganization dynamics that are governed by the characteristics of peptide sequence and oligomer size.

  4. Conformational Dynamics of Response Regulator RegX3 from Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Ashfaq Ahmad

    Full Text Available Two-component signal transduction systems (TCS are vital for adaptive responses to various environmental stresses in bacteria, fungi and even plants. A TCS typically comprises of a sensor histidine kinase (SK with its cognate response regulator (RR, which often has two domains-N terminal receiver domain (RD and C terminal effector domain (ED. The histidine kinase phosphorylates the RD to activate the ED by promoting dimerization. However, despite significant progress on structural studies, how RR transmits activation signal from RD to ED remains elusive. Here we analyzed active to inactive transition process of OmpR/PhoB family using an active conformation of RegX3 from Mycobacterium tuberculosis as a model system by computational approaches. An inactive state of RegX3 generated from 150 ns molecular dynamic simulation has rotameric conformations of Thr79 and Tyr98 that are generally conserved in inactive RRs. Arg81 in loop β4α4 acts synergistically with loop β1α1 to change its interaction partners during active to inactive transition, potentially leading to the N-terminal movement of RegX3 helix α1. Global conformational dynamics of RegX3 is mainly dependent on α4β5 region, in particular seven 'hot-spot' residues (Tyr98 to Ser104, adjacent to which several coevolved residues at dimeric interface, including Ile76-Asp96, Asp97-Arg111 and Glu24-Arg113 pairs, are critical for signal transduction. Taken together, our computational analyses suggest a molecular linkage between Asp phosphorylation, proximal loops and α4β5α5 dimeric interface during RR active to inactive state transition, which is not often evidently defined from static crystal structures.

  5. Structure and dynamics of water in crowded environments slows down peptide conformational changes

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Cheng; Prada-Gracia, Diego; Rao, Francesco, E-mail: francesco.rao@frias.uni-freiburg.de [Freiburg Institute for Advanced Studies, School of Soft Matter Research, Albertstrasse 19, 79104 Freiburg im Breisgau (Germany)

    2014-07-28

    The concentration of macromolecules inside the cell is high with respect to conventional in vitro experiments or simulations. In an effort to characterize the effects of crowding on the thermodynamics and kinetics of disordered peptides, molecular dynamics simulations were run at different concentrations by varying the number of identical weakly interacting peptides inside the simulation box. We found that the presence of crowding does not influence very much the overall thermodynamics. On the other hand, peptide conformational dynamics was found to be strongly affected, resulting in a dramatic slowing down at larger concentrations. The observation of long lived water bridges between peptides at higher concentrations points to a nontrivial role of the solvent in the altered peptide kinetics. Our results reinforce the idea for an active role of water in molecular crowding, an effect that is expected to be relevant for problems influenced by large solvent exposure areas like in intrinsically disordered proteins.

  6. Adaptive lambda square dynamics simulation: an efficient conformational sampling method for biomolecules.

    Science.gov (United States)

    Ikebe, Jinzen; Sakuraba, Shun; Kono, Hidetoshi

    2014-01-05

    A novel, efficient sampling method for biomolecules is proposed. The partial multicanonical molecular dynamics (McMD) was recently developed as a method that improved generalized ensemble (GE) methods to focus sampling only on a part of a system (GEPS); however, it was not tested well. We found that partial McMD did not work well for polylysine decapeptide and gave significantly worse sampling efficiency than a conventional GE. Herein, we elucidate the fundamental reason for this and propose a novel GEPS, adaptive lambda square dynamics (ALSD), which can resolve the problem faced when using partial McMD. We demonstrate that ALSD greatly increases the sampling efficiency over a conventional GE. We believe that ALSD is an effective method and is applicable to the conformational sampling of larger and more complicated biomolecule systems. Copyright © 2013 Wiley Periodicals, Inc.

  7. 皮带传动中动弧角曲面的分析%The analysis of the dynamic arc angle surface in belt transmission

    Institute of Scientific and Technical Information of China (English)

    屈翔; 邱香; 廖林清; 谢明; 张君

    2011-01-01

    通过推导,得到皮带初拉力、皮带有效拉力和皮带动弧角这三个重要参数形成曲面所列应的曲面方程,并定义为动弧角曲面方程,在已知其中任意两参数的情况下,可计算第三参数的大小.分析动弧角曲面特性,研究当量摩擦系数对动弧角曲面的影响,及曲面三参数之间的重要关系.%Three parameters including belt initiol tension ,effective belt tension and dynamic arc angle are derived to form the arc angle surface which is correspondent to an arc angle surface equation and this equation is defined as the dynamic arc angle surface equotion.In the eqution,with two of the three parmaeters known,the third paramter can be calculated out. The characteristics of the dynamic arc angle surface is analyzed and the effect of the equivalent coefficient of friction on the dynamic arc angle surface as well as the relationship among the three parameters of the arc angle surface is studied.

  8. Conformational Search on the Lewis X Structure by Molecular Dynamic: Study of Tri- and Pentasaccharide

    Directory of Open Access Journals (Sweden)

    N. Khebichat

    2012-01-01

    Full Text Available Carbohydrates play vital roles in many biological processes, such as recognition, adhesion, and signalling between cells. The Lewis X determinant is a trisaccharide fragment implicated as a specific differentiation antigen, tumor antigen, and key component of the ligand for the endothelial leukocyte adhesion molecule, so it is necessary or essential to determine and to know their conformational and structural properties. In this work, conformational analysis was performed using molecular dynamics (MD simulation with the AMBER10 program package in order to study the dynamic behavior of of the Lewis X trisaccharide (β-D-Gal-(1,4-[α-L-Fuc-(1,3]-β-D-GlcNAc-OMe and the Lewis X pentasaccharide (β-D-Gal-(1,4-[α-L-Fuc-(1,3]-β-D-GlcNAc-(1,3-β-D-Gal-(1,4-β-D-Glu-OMe in explicit water model at 300 K for 10 ns using the GLYCAM 06 force field.

  9. Dose conformation to the spine during palliative treatments using dynamic wedges

    Energy Technology Data Exchange (ETDEWEB)

    Ormsby, Matthew A., E-mail: Matthew.Ormsby@usoncology.com [West Texas Cancer Center at Medical Center Hospital, Odessa, TX (United States); Herndon, R. Craig; Kaczor, Joseph G. [West Texas Cancer Center at Medical Center Hospital, Odessa, TX (United States)

    2013-07-01

    Radiation therapy is commonly used to alleviate pain associated with metastatic disease of the spine. Often, isodose lines are manipulated using dynamic or physical wedges to encompass the section of spine needing treatment while minimizing dose to normal tissue. We will compare 2 methods used to treat the entire thoracic spine. The first method treats the thoracic spine with a single, nonwedged posterior-anterior (PA) field. Dose is prescribed to include the entire spine. Isodose lines tightly conform to the top and bottom vertebrae, but vertebrae between these 2 received more than enough coverage. The second method uses a combination of wedges to create an isodose line that mimics the curvature of the thoracic spine. This “C”-shaped curvature is created by overlapping 2 fields with opposing dynamic wedges. Machine constraints limit the treatment length and therefore 2 isocenters are used. Each of the 2 PA fields contributes a portion of the total daily dose. This technique creates a “C”-shaped isodose line that tightly conforms to the thoracic spine, minimizing normal tissue dose. Spinal cord maximum dose is reduced, as well as mean dose to the liver, esophagus, and heart.

  10. Study of Conformation and Dynamics of Molecules Adsorbed in Zeolites by 1H NMR

    Science.gov (United States)

    Michel, Dieter; Bohlmann, Winfried; Roland, Jorg; Mulla-Osman, Samir

    The chapter Study of Conformation and Dynamics of Molecules Adsorbed in Zeolites by 1H NMR is concerned with the application of high-resolution (HR) solid-state NMR techniques to study the behavior of molecules adsorbed on surfaces of nanoporous solids, such as zeolitic molecular sieves. This includes a combined or alternative application of conventional high-resolution NMR methods and of high-resolution solid-state NMR techniques, including magic-angle sample spinning (MAS), cross-polarization (CP), high-power decoupling and appropriate multiple-pulse sequences for two- or higher dimensional NMR and multiple-quantum spectroscopy. The interaction of adsorbed molecules with adsorption centers in the internal surfaces of porous solids does not only lead to changes in the reorientational and translational mobility of the molecular species but influences also the molecular conformation. Examples will be given for simple olefins in interaction with inner zeolite surfaces. Conclusions about the correlation times of the internal reorientational and translational dynamics are derived in complete agreement with the conclusion obtained from diffusion coefficients by means of PFG NMR (second chapter). Since the methodical approach of HR MAS NMR in heterogeneous systems presented here is also valuable for the investigation of lyotropic crystalline phases using HR MAS NMR (in Chap. 12) And for the NMR studies of cartilage (in Chap. 13) it was also the aim of this chapter to elucidate also the methodical background of these measurements in some more detail.

  11. Two-dimensional NMR investigations of the dynamic conformations of phospholipids and liquid crystals

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Mei [Univ. of California, Berkeley, CA (United States). Applied Science and Technology

    1996-05-01

    Two-dimensional 13C, 1H, and 31P nuclear magnetic resonance (NMR) techniques are developed and used to study molecular structure and dynamics in liquid-crystalline systems, primarily phospholipids and nematic liquid crystals. NMR spectroscopy characterizes molecular conformation in terms of orientations and distances of molecular segments. In anisotropically mobile systems, this is achieved by measuring motionally-averaged nuclear dipolar couplings and chemical shift anisotropies. The short-range couplings yield useful bond order parameters, while the long-range interactions constrain the overall conformation. In this work, techniques for probing proton dipolar local fields are further developed to obtain highlyresolved dipolar couplings between protons and rare spins. By exploiting variable-angle sample spinning techniques, orientation-sensitive NMR spectra are resolved according to sitespecific isotropic chemical shifts. Moreover, the signs and magnitudes of various short-range dipolar couplings are obtained. They are used in novel theoretical analyses that provide information about segmental orientations and their distributions. Such information is obtained in a model-independent fashion or with physically reasonable assumptions. The structural investigation of phospholipids is focused on the dynam

  12. FRET Fluctuation Spectroscopy of Diffusing Biopolymers: Contributions of Conformational Dynamics and Translational Diffusion

    Science.gov (United States)

    Gurunathan, Kaushik; Levitus, Marcia

    2009-01-01

    The use of Fluorescence Correlation Spectroscopy (FCS) to study conformational dynamics in diffusing biopolymers requires that the contributions to the signal due to translational diffusion are separated from those due to conformational dynamics. A simple approach that has been proposed to achieve this goal involves the analysis of fluctuations in Fluorescence Resonance Energy Transfer (FRET) efficiency. In this work, we investigate the applicability of this methodology by combining Monte Carlo simulations and experiments. Results show that diffusion does not contribute to the measured fluctuations in FRET efficiency in conditions where the relaxation time of the kinetic process is much shorter than the mean transit time of the molecules in the optical observation volume. However, in contrast to what has been suggested in previous work, the contributions of diffusion are otherwise significant. Neglecting the contributions of diffusion can potentially lead to an erroneous interpretation of the kinetic mechanisms. As an example, we demonstrate that the analysis of FRET fluctuations in terms of a purely kinetic model would generally lead to the conclusion that the system presents complex kinetic behavior even for an idealized two-state system PMID:20030305

  13. Cosmological consequences of nearly conformal dynamics at the TeV scale

    Science.gov (United States)

    Konstandin, Thomas; Servant, Géraldine

    2011-12-01

    Nearly conformal dynamics at the TeV scale as motivated by the hierarchy problem can be characterized by a stage of significant supercooling at the electroweak epoch. This has important cosmological consequences. In particular, a common assumption about the history of the universe is that the reheating temperature is high, at least high enough to assume that TeV-mass particles were once in thermal equilibrium. However, as we discuss in this paper, this assumption is not well justified in some models of strong dynamics at the TeV scale. We then need to reexamine how to achieve baryogenesis in these theories as well as reconsider how the dark matter abundance is inherited. We argue that baryonic and dark matter abundances can be explained naturally in these setups where reheating takes place by bubble collisions at the end of the strongly first-order phase transition characterizing conformal symmetry breaking, even if the reheating temperature is below the electroweak scale ~ 100 GeV. In particular, non-thermal production of heavy WIMPs during bubble collisions becomes a well-motivated possibility. We also discuss inflation as well as gravity wave smoking gun signatures of this class of models.

  14. Cosmological Consequences of Nearly Conformal Dynamics at the TeV scale

    CERN Document Server

    Konstandin, Thomas

    2011-01-01

    Nearly conformal dynamics at the TeV scale as motivated by the hierarchy problem can be characterized by a stage of significant supercooling at the electroweak epoch. This has important cosmological consequences. In particular, a common assumption about the history of the universe is that the reheating temperature is high, at least high enough to assume that TeV-mass particles were once in thermal equilibrium. However, as we discuss in this paper, this assumption is not well justified in some models of strong dynamics at the TeV scale. We then need to reexamine how to achieve baryogenesis in these theories as well as reconsider how the dark matter abundance is inherited. We argue that baryonic and dark matter abundances can be explained naturally in these setups where reheating takes place by bubble collisions at the end of the strongly first-order phase transition characterizing conformal symmetry breaking, even if the reheating temperature is below the electroweak scale $\\sim 100$ GeV. We also discuss infla...

  15. Probe conformational dynamics of proteins in aqueous solutions by terahertz spectroscopy

    Science.gov (United States)

    Vinh, Nguyen Q.

    2016-10-01

    Proteins solvated in their biologically milieu are expected to exhibit strong absorption in the terahertz frequencies, that contain information on their global and sub-global collective vibrational modes (conformational dynamics) and global dynamic correlations among solvent water and proteins. The dynamics play an important role in enzymatic activities of proteins, but obtaining an accurate and quantitative pictures of these activities, however, is challenging due to the strong absorption of water. In response, we have developed the world's highest precision, highest sensitivity terahertz-frequency domain spectrometer and a standard terahertz-time domain system to probe the collective dynamics of proteins in aqueous solutions. Operating over the frequency range from 5 GHz up to 3 THz, our spectrometers provide an unparalleled ability to probe directly such questions as the hydration level, the dynamics of water and hydrated proteins over the 100 fs to 1 ns timescale. Employing an effective medium approximation to describe the complex dielectric response of the solvated proteins in solution we find that proteins are surrounded by a loosely and tightly held layers of water molecules that behave as if they are an integral part of the protein. The number of water molecules in the protein hydration shells varies with proteins, which can tell us the average surface structure of proteins. These measurements shed light on the macromolecular motions of proteins in their biologically relevant environment.

  16. Real-time dynamic MLC tracking for inversely optimized arc radiotherapy

    DEFF Research Database (Denmark)

    Falk, Marianne; af Rosenschöld, Per Munck; Keall, Paul;

    2010-01-01

    Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory....

  17. Real-time dynamic MLC tracking for inversely optimized arc radiotherapy

    DEFF Research Database (Denmark)

    Falk, Marianne; af Rosenschöld, Per Munck; Keall, Paul

    2010-01-01

    Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory.......Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory....

  18. Dynamic paleogeography of the Jurassic Andean Basin: pattern of transgression and localisation of main straits through the magmatic arc

    Directory of Open Access Journals (Sweden)

    J-C. Vicente

    2005-03-01

    Full Text Available The paleogeographic evolution of the Jurassic Andean retroarc basin is examined at a global scale for the Central Andes. In this paper, it is called for the striking continuity and lasting of the active volcanic arc. Both direct and indirect sedimentologic evidences allow to locate the western border (insular of the basin and opposite it with the eastern border (cratonic. Emphasis is placed on the volcaniclastic deposits and synsedimentary structures associated with this insular border. It is concluded that the arc magmatic activity has contributed considerably in sediment supply to the basin. Extent and continuity of the arc implies to locate the straits connecting with the Paleopacific. Systematic check of the time of transgressions coupled with sequential facies analysis provides a dynamic outlook of the transgressive process. Sectors with early transgression allow to distinguish two main gulfs of passage through the arc from which waters have progressed lengthwise at the same time northward and southward in a narrow retroarc furrow : the first at latitude of Taltal (25°S, the second at latitude of Curepto (35°S. Both initiated in the upper Triassic and extended during the Hettangian. The evolution as separate basins (Tarapacá and Aconcagua-Neuquén ended by fusion in middle Pliensbachian giving rise to a continuous elongated basin from Chubut to northern Peru. The remarkable continuity and narrowness of the Andean Basin leaves no doubt about its tectonic control. This stems to its geotectonic setting as a typical retroarc basin adjacent to a very active magmatic arc and explains the extreme mobility of its insular margin characterized by a huge volcanoclastic apron with associated debris flows and turbidites.

  19. Ethnic difference in risk of toxicity in prostate cancer patients treated with dynamic arc radiation therapy.

    Science.gov (United States)

    Lopez Guerra, Jose L; Matute, Raul; Puebla, Fernando; Sánchez-Reyes, Alberto; Pontes, Beatriz; Rubio, Cristina; Nepomuceno, Isabel; Acevedo, Catalina; Isa, Nicolas; Lengua, Rafael; Praena-Fernandez, Juan Manuel; del Campo, Eleonor Rivin; Ortiz, Maria Jose; Azinovic, Ignacio

    2015-01-01

    The objective of this study was to assess the influence of ethnicity on toxicity in patients treated with dynamic arc radiation therapy (ART) for prostate cancer (PC). From June 2006 to May 2012, 162 cT1-T3 cN0 cM0 PC patients were treated with ART (primary diagnosis, n = 125; post-prostatectomy/brachytherapy biochemical recurrence, n = 26; adjuvant post-prostatectomy, n = 11) at 2 institutions. Forty-five patients were Latin Americans and 117 were Europeans. The dose prescribed to the prostate ranged between 68 Gy and 81 Gy. The median age was 69 years (range 43-87 years). The median follow-up was 18 months (range 2-74 months). Overall, only 3 patients died, none due to a cancer-related cause. Biochemical recurrence was seen in 7 patients. The rates of acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities were 19.7% and 17%, respectively. Only 1 patient experienced acute grade 3 GI toxicity, whereas 11 patients (6.7%) experienced acute grade 3 GU toxicity. Multivariate analysis showed that undergoing whole pelvic lymph node irradiation was associated with a higher grade of acute GI toxicity (OR: 3.46; p = 0.003). In addition, older age was marginally associated with a higher grade of acute GI toxicity (OR: 2.10; p = 0.074). Finally, ethnicity was associated with acute GU toxicity: Europeans had lower-grade toxicity (OR: 0.27; p = 0.001). Our findings suggest an ethnic difference in GU toxicity for PC patients treated with ART. In addition, we found that ART is associated with a very low risk of severe toxicity and a low recurrence rate.

  20. Dynamic Aberration Correction for Conformal Window of High-Speed Aircraft Using Optimized Model-Based Wavefront Sensorless Adaptive Optics

    Science.gov (United States)

    Dong, Bing; Li, Yan; Han, Xin-li; Hu, Bin

    2016-01-01

    For high-speed aircraft, a conformal window is used to optimize the aerodynamic performance. However, the local shape of the conformal window leads to large amounts of dynamic aberrations varying with look angle. In this paper, deformable mirror (DM) and model-based wavefront sensorless adaptive optics (WSLAO) are used for dynamic aberration correction of an infrared remote sensor equipped with a conformal window and scanning mirror. In model-based WSLAO, aberration is captured using Lukosz mode, and we use the low spatial frequency content of the image spectral density as the metric function. Simulations show that aberrations induced by the conformal window are dominated by some low-order Lukosz modes. To optimize the dynamic correction, we can only correct dominant Lukosz modes and the image size can be minimized to reduce the time required to compute the metric function. In our experiment, a 37-channel DM is used to mimic the dynamic aberration of conformal window with scanning rate of 10 degrees per second. A 52-channel DM is used for correction. For a 128 × 128 image, the mean value of image sharpness during dynamic correction is 1.436 × 10−5 in optimized correction and is 1.427 × 10−5 in un-optimized correction. We also demonstrated that model-based WSLAO can achieve convergence two times faster than traditional stochastic parallel gradient descent (SPGD) method. PMID:27598161

  1. Dynamic Aberration Correction for Conformal Window of High-Speed Aircraft Using Optimized Model-Based Wavefront Sensorless Adaptive Optics.

    Science.gov (United States)

    Dong, Bing; Li, Yan; Han, Xin-Li; Hu, Bin

    2016-09-02

    For high-speed aircraft, a conformal window is used to optimize the aerodynamic performance. However, the local shape of the conformal window leads to large amounts of dynamic aberrations varying with look angle. In this paper, deformable mirror (DM) and model-based wavefront sensorless adaptive optics (WSLAO) are used for dynamic aberration correction of an infrared remote sensor equipped with a conformal window and scanning mirror. In model-based WSLAO, aberration is captured using Lukosz mode, and we use the low spatial frequency content of the image spectral density as the metric function. Simulations show that aberrations induced by the conformal window are dominated by some low-order Lukosz modes. To optimize the dynamic correction, we can only correct dominant Lukosz modes and the image size can be minimized to reduce the time required to compute the metric function. In our experiment, a 37-channel DM is used to mimic the dynamic aberration of conformal window with scanning rate of 10 degrees per second. A 52-channel DM is used for correction. For a 128 × 128 image, the mean value of image sharpness during dynamic correction is 1.436 × 10(-5) in optimized correction and is 1.427 × 10(-5) in un-optimized correction. We also demonstrated that model-based WSLAO can achieve convergence two times faster than traditional stochastic parallel gradient descent (SPGD) method.

  2. A dynamic compensation strategy to correct patient-positioning errors in conformal prostate radiotherapy.

    Science.gov (United States)

    Lauve, A D; Siebers, J V; Crimaldi, A J; Hagan, M P; Kealla, P J

    2006-06-01

    Traditionally, pretreatment detected patient-positioning errors have been corrected by repositioning the couch to align the patient to the treatment beam. We investigated an alternative strategy: aligning the beam to the patient by repositioning the dynamic multileaf collimator and adjusting the beam weights, termed dynamic compensation. The purpose of this study was to determine the geometric range of positioning errors for which the dynamic compensation method is valid in prostate cancer patients treated with three-dimensional conformal radiotherapy. Twenty-five previously treated prostate cancer patients were replanned using a four-field technique to deliver 72 Gy to 95% of the planning target volume (PTV). Patient-positioning errors were introduced by shifting the patient reference frame with respect to the treatment isocenter. Thirty-six randomly selected isotropic displacements with magnitudes of 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 cm were sampled for each patient, for a total of 5400 errors. Dynamic compensation was used to correct each of these errors by conforming the beam apertures to the new target position and adjusting the monitor units using inverse-square and off-axis factor corrections. The dynamic compensation plans were then compared with the original treatment plans via dose-volume histogram (DVH) analysis. Changes of more than 5% of the prescription dose, 3.6 Gy, were deemed significant. Compared with the original treatment plans, dynamic compensation produced small discrepancies in isodose distributions and DVH analyses. These differences increased with the magnitudes of the initial patient-positioning errors. Coverage of the PTV was excellent: D95 and Dmean were not increased or decreased by more than 5% of the prescription dose, and D5 was not decreased by more than 5% of the prescription dose for any of the 5400 simulated positioning errors. D5 was increased by more than 5% of the prescription dose in only three of the 5400 positioning errors

  3. Dynamic Optimization and Conformity in Health Behavior and Life Enjoyment over the Life Cycle

    Directory of Open Access Journals (Sweden)

    Hernan Daniel Bejarano

    2015-06-01

    Full Text Available This article examines individual and social influences on investments in health and enjoyment from immediate consumption. Our lab experiment mimics the problem of health investment over a lifetime (Grossman 1972a, 1972b. Incentives to find the appropriate expenditures on life enjoyment and health are given by making in each period come period a function of previous health investments. In order to model social effects in the experiment, we randomly assigned individuals to chat/observation groups. Groups were permitted to freely chat between repeated lifetimes. Two treatments were employed: In the Independent-rewards treatment, an individual’s rewards from investments in life enjoyment depend only on his choice and in the Interdependent-rewards treatment; rewards not only depend on an individual’s choices but also on their similarity to the choices of the others in their group, generating a premium on conformity. The principal hypothesis is that gains from conformity increase variance in health behavior among groups and can lead to suboptimal performance. We tested three predictions and each was supported by the data: the Interdependent-rewards treatment 1 decreased within-group variance, 2 increased between-group variance, and 3 increased the likelihood of behavior far from the optimum with respect to the dynamic problem. We also test and find support for a series of subsidiary hypotheses. We found: 4 Subjects engaged in helpful chat in both treatments; 5 there was significant heterogeneity among both subjects and groups in chat frequencies; and 6 chat was most common early in the experiment, and 7 the interdependent rewards treatment increased strategic chat frequency. Incentives for conformity appear to promote prosocial behavior, but also increase variance among groups, leading to convergence on suboptimal strategies for some groups. We discuss these results in light of the growing literature focusing on social networks and health outcomes.

  4. Assessing polyglutamine conformation in the nucleating event by molecular dynamics simulations.

    Science.gov (United States)

    Miettinen, Markus S; Knecht, Volker; Monticelli, Luca; Ignatova, Zoya

    2012-08-30

    Polyglutamine (polyQ) diseases comprise a group of dominantly inherited pathology caused by an expansion of an unstable polyQ stretch which is presumed to form β-sheets. Similar to other amyloid pathologies, polyQ amyloidogenesis occurs via a nucleated polymerization mechanism, and proceeds through energetically unfavorable nucleus whose existence and structure are difficult to detect. Here, we use atomistic molecular dynamics simulations in explicit solvent to assess the conformation of the polyQ stretch in the nucleus that initiates polyQ fibrillization. Comparison of the kinetic stability of various structures of polyQ peptide with a Q-length in the pathological range (Q40) revealed that steric zipper or nanotube-like structures (β-nanotube or β-pseudohelix) are not kinetically stable enough to serve as a template to initiate polyQ fibrillization as opposed to β-hairpin-based (β-sheet and β-sheetstack) or α-helical conformations. The selection of different structures of the polyQ stretch in the aggregation-initiating event may provide an alternative explanation for polyQ aggregate polymorphism.

  5. Structural Dynamics of the Magnesium-bound Conformation of CorA in a lipid bilayer

    Science.gov (United States)

    Dalmas, Olivier; Cuello, Luis G.; Jogini, Vishwanath; Cortes, D. Marien; Roux, Benoit; Perozo, Eduardo

    2010-01-01

    Summary The transmembrane conformation of Thermotoga maritima CorA, a Magnesium transport system, has been studied in it’s Mg2+-bound form by site-directed spin labeling and electron paramagnetic resonance spectroscopy. Probe mobility together with accessibility data were used to evaluate the overall dynamics and relative arrangement of individual transmembrane segments TM1 and TM2. TM1 extends toward the cytoplasmic side creating a water filled cavity, while TM2 is located in the periphery of the oligomer, contacting the lipid bilayer. A structural model for the conserved extracellular loop was generated based on EPR data and MD simulations, in which residue E316 is located towards the fivefold symmetry axis in position to electrostatically influence divalent ion translocation. Electrostatic analyses of our model suggest that, in agreement with the crystal structure, Mg2+ -bound CorA is in a close conformation. The present results suggest that long-range structural rearrangements are necessary to allow Mg2+ translocation. PMID:20637423

  6. Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1.

    Science.gov (United States)

    Briones, Rodolfo; Weichbrodt, Conrad; Paltrinieri, Licia; Mey, Ingo; Villinger, Saskia; Giller, Karin; Lange, Adam; Zweckstetter, Markus; Griesinger, Christian; Becker, Stefan; Steinem, Claudia; de Groot, Bert L

    2016-09-20

    The voltage-dependent anion channel 1 (VDAC-1) is an important protein of the outer mitochondrial membrane that transports energy metabolites and is involved in apoptosis. The available structures of VDAC proteins show a wide β-stranded barrel pore, with its N-terminal α-helix (N-α) bound to its interior. Electrophysiology experiments revealed that voltage, its polarity, and membrane composition modulate VDAC currents. Experiments with VDAC-1 mutants identified amino acids that regulate the gating process. However, the mechanisms for how these factors regulate VDAC-1, and which changes they trigger in the channel, are still unknown. In this study, molecular dynamics simulations and single-channel experiments of VDAC-1 show agreement for the current-voltage relationships of an "open" channel and they also show several subconducting transient states that are more cation selective in the simulations. We observed voltage-dependent asymmetric distortions of the VDAC-1 barrel and the displacement of particular charged amino acids. We constructed conformational models of the protein voltage response and the pore changes that consistently explain the protein conformations observed at opposite voltage polarities, either in phosphatidylethanolamine or phosphatidylcholine membranes. The submicrosecond VDAC-1 voltage response shows intrinsic structural changes that explain the role of key gating amino acids and support some of the current gating hypotheses. These voltage-dependent protein changes include asymmetric barrel distortion, its interaction with the membrane, and significant displacement of N-α amino acids.

  7. Structural dynamics of the magnesium-bound conformation of CorA in a lipid bilayer.

    Science.gov (United States)

    Dalmas, Olivier; Cuello, Luis G; Jogini, Vishwanath; Cortes, D Marien; Roux, Benoit; Perozo, Eduardo

    2010-07-14

    The transmembrane conformation of Thermotoga maritima CorA, a magnesium transport system, has been studied in its Mg(2+)-bound form by site-directed spin labeling and electron paramagnetic resonance spectroscopy. Probe mobility together with accessibility data were used to evaluate the overall dynamics and relative arrangement of individual transmembrane segments TM1 and TM2. TM1 extends toward the cytoplasmic side creating a water-filled cavity, while TM2 is located in the periphery of the oligomer, contacting the lipid bilayer. A structural model for the conserved extracellular loop was generated based on EPR data and MD simulations, in which residue E316 is located toward the five-fold symmetry axis in position to electrostatically influence divalent ion translocation. Electrostatic analysis of our model suggest that, in agreement with the crystal structure, Mg(2+) -bound CorA is in a closed conformation. The present results suggest that long-range structural rearrangements are necessary to allow Mg(2+) translocation. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Wang-Landau molecular dynamics technique to search for low-energy conformational space of proteins

    CERN Document Server

    Nagasima, Takehiro; Mitsui, Takashi; Nishikawa, Ken-Ichi

    2007-01-01

    Multicanonical molecular dynamics (MD) is a powerful technique for sampling conformations on rugged potential surfaces such as protein. However, it is notoriously difficult to estimate the multicanonical temperature effectively. Wang and Landau developed a convenient method for estimating the density of states based on a multicanonical Monte Carlo method. In their method, the density of states is calculated autonomously during a simulation. In this paper we develop a set of techniques to effectively apply the Wang-Landau method to MD simulations. In the multicanonical MD, the estimation of the derivative of the density of states is critical. In order to estimate it accurately, we devise two original improvements. First, the correction for the density of states is made smooth by using the Gaussian distribution obtained by a short canonical simulation. Second, an approximation is applied to the derivative, which is based on the Gaussian distribution and the multiple weighted histogram technique. A test of this ...

  9. NATO Advanced Study Institute on Photophysical and Photochemical Tools in Polymer Science : Conformation, Dynamics, Morphology

    CERN Document Server

    1986-01-01

    In 1980 the New York Academy of Sciences sponsored a three-day conference on luminescence in biological and synthetic macromolecules. After that meeting, Professor Frans DeSchryver and I began to discuss the possibility of organizing a different kind of meeting, with time for both informal and in-depth discussions, to examine certain aspects of the application of fluorescence and phosphorescence spectroscopy to polymers. Our ideas developed through discussions with many others, particularly Professor Lucien Monnerie. By 1983, when we submitted our proposal to NATO for an Advanced Study Institute, the area had grown enormous ly. It is interesting in retrospect to look back on the points which emerged from these discussions as the basis around which the scientific program would be organized and the speakers chosen. We decided early on to focus on applications of these methods to provide information about polymer molecules and polymer systems: The topics would all relate to the conformation and dynamics of macro...

  10. Water-mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study.

    Science.gov (United States)

    Sankararamakrishnan, R; Sansom, M S

    1995-12-27

    The ion channel of the nicotinic acetylcholine receptor is a water-filled pore formed by five M2 helix segments, one from each subunit. Molecular dynamics simulations on bundles of five M2 alpha 7 helices surrounding a central column of water and with caps of water molecules at either end of the pore have been used to explore the effects of intrapore water on helix packing. Interactions of water molecules with the N-terminal polar sidechains lead to a conformational transition from right- to left-handed supercoils during these stimulations. These studies reveal that the pore formed by the bundle of M2 helices is flexible. A structural role is proposed for water molecules in determining the geometry of bundles of isolated pore-forming helices.

  11. Mapping the Conformational Dynamics of E-selectin upon Interaction with its Ligands

    KAUST Repository

    Aleisa, Fajr A

    2013-05-15

    Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. The adhesion of cells (expressing ligands) to the endothelium (expressing the selectin i.e.,E-selectin) occurs through spatio-temporally regulated interactions that are mediated by multiple intra- and inter-cellular components. The mechanism of cell adhesion is investigated primarily using ensemble-based experiments, which provides indirect information about how individual molecules work in such a complex system. Recent developments in single-molecule (SM) fluorescence detection allow for the visualization of individual molecules with a good spatio-temporal resolution nanometer spatial resolution and millisecond time resolution). Furthermore, advanced SM fluorescence techniques such as Förster Resonance Energy Transfer (FRET) and super-resolution microscopy provide unique opportunities to obtain information about nanometer-scale conformational dynamics of proteins as well as nano-scale architectures of biological samples. Therefore, the state-of-the-art SM techniques are powerful tools for investigating complex biological system such as the mechanism of cell adhesion. In this project, several constructs of fluorescently labeled E-selectin will be used to study the conformational dynamics of E-selectin binding to its ligand(s) using SM-FRET and combination of SM-FRET and force microscopy. These studies will be beneficial to fully understand the mechanistic details of cell adhesion and migration of cells using the established model system of hematopoietic stem cells (HSCs) adhesion to the selectin expressing endothelial cells (such as the E-selectin expressing endothelial cells in the bone marrow).

  12. Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer.

    Science.gov (United States)

    Adhikary, Suraj; Deredge, Daniel J; Nagarajan, Anu; Forrest, Lucy R; Wintrode, Patrick L; Singh, Satinder K

    2017-03-07

    Neurotransmitter:sodium symporters (NSSs) are integral membrane proteins responsible for the sodium-dependent reuptake of small-molecule neurotransmitters from the synaptic cleft. The symporters for the biogenic amines serotonin (SERT), dopamine (DAT), and norepinephrine (NET) are targets of multiple psychoactive agents, and their dysfunction has been implicated in numerous neuropsychiatric ailments. LeuT, a thermostable eubacterial NSS homolog, has been exploited as a model protein for NSS members to canvass the conformational mechanism of transport with a combination of X-ray crystallography, cysteine accessibility, and solution spectroscopy. Despite yielding remarkable insights, these studies have primarily been conducted with protein in the detergent-solubilized state rather than embedded in a membrane mimic. In addition, solution spectroscopy has required site-specific labeling of nonnative cysteines, a labor-intensive process occasionally resulting in diminished transport and/or binding activity. Here, we overcome these limitations by reconstituting unlabeled LeuT in phospholipid bilayer nanodiscs, subjecting them to hydrogen-deuterium exchange coupled with mass spectrometry (HDX-MS), and facilitating interpretation of the data with molecular dynamics simulations. The data point to changes of accessibility and dynamics of structural elements previously implicated in the transport mechanism, in particular transmembrane helices (TMs) 1a and 7 as well as extracellular loops (ELs) 2 and 4. The results therefore illuminate the value of this strategy for interrogating the conformational mechanism of the more clinically significant mammalian membrane proteins including SERT and DAT, neither of which tolerates complete removal of endogenous cysteines, and whose activity is heavily influenced by neighboring lipids.

  13. Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

    CERN Document Server

    Yusuff, Olaniyi K; Bussi, Giovanni; Raugei, Simone

    2012-01-01

    Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\\alpha}1{\\beta}2 and {\\alpha}2{\\b...

  14. Heteronuclear Adiabatic Relaxation Dispersion (HARD) for quantitative analysis of conformational dynamics in proteins.

    Science.gov (United States)

    Traaseth, Nathaniel J; Chao, Fa-An; Masterson, Larry R; Mangia, Silvia; Garwood, Michael; Michaeli, Shalom; Seelig, Burckhard; Veglia, Gianluigi

    2012-06-01

    NMR relaxation methods probe biomolecular motions over a wide range of timescales. In particular, the rotating frame spin-lock R(1ρ) and Carr-Purcell-Meiboom-Gill (CPMG) R(2) experiments are commonly used to characterize μs to ms dynamics, which play a critical role in enzyme folding and catalysis. In an effort to complement these approaches, we introduced the Heteronuclear Adiabatic Relaxation Dispersion (HARD) method, where dispersion in rotating frame relaxation rate constants (longitudinal R(1ρ) and transverse R(2ρ)) is created by modulating the shape and duration of adiabatic full passage (AFP) pulses. Previously, we showed the ability of the HARD method to detect chemical exchange dynamics in the fast exchange regime (k(ex)∼10(4)-10(5) s(-1)). In this article, we show the sensitivity of the HARD method to slower exchange processes by measuring R(1ρ) and R(2ρ) relaxation rates for two soluble proteins (ubiquitin and 10C RNA ligase). One advantage of the HARD method is its nominal dependence on the applied radio frequency field, which can be leveraged to modulate the dispersion in the relaxation rate constants. In addition, we also include product operator simulations to define the dynamic range of adiabatic R(1ρ) and R(2ρ) that is valid under all exchange regimes. We conclude from both experimental observations and simulations that this method is complementary to CPMG-based and rotating frame spin-lock R(1ρ) experiments to probe conformational exchange dynamics for biomolecules. Finally, this approach is germane to several NMR-active nuclei, where relaxation rates are frequency-offset independent. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Young, E-mail: eyhan@uams.edu [Department of Radiation Oncology, University of Arkansas Medical Sciences, Little Rock, AR (United States); Kim, Dong-Wook [Department of Radiation Oncology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Zhang, Xin; Penagaricano, Jose; Liang, Xiaoying; Hardee, Matthew; Morrill, Steve; Ratanatharathorn, Vaneerat [Department of Radiation Oncology, University of Arkansas Medical Sciences, Little Rock, AR (United States)

    2015-10-01

    It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently, the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.

  16. Searching the conformational complexity and binding properties of HDAC6 through docking and molecular dynamic simulations.

    Science.gov (United States)

    Sixto-López, Yudibeth; Bello, Martiniano; Rodríguez-Fonseca, Rolando Alberto; Rosales-Hernández, Martha Cecilia; Martínez-Archundia, Marlet; Gómez-Vidal, José Antonio; Correa-Basurto, José

    2017-10-01

    Histone deacetylases (HDACs) are a family of proteins involved in the deacetylation of histones and other non-histones substrates. HDAC6 belongs to class II and shares similar biological functions with others of its class. Nevertheless, its three-dimensional structure that involves the catalytic site remains unknown for exploring the ligand recognition properties. Therefore, in this contribution, homology modeling, 100-ns-long Molecular Dynamics (MD) simulation and docking calculations were combined to explore the conformational complexity and binding properties of the catalytic domain 2 from HDAC6 (DD2-HDAC6), for which activity and affinity toward five different ligands have been reported. Clustering analysis allowed identifying the most populated conformers present during the MD simulation, which were used as starting models to perform docking calculations with five DD2-HDAC6 inhibitors: Cay10603 (CAY), Rocilinostat (RCT), Tubastatin A (TBA), Tubacin (TBC), and Nexturastat (NXT), and then were also submitted to 100-ns-long MD simulations. Docking calculations revealed that the five inhibitors bind at the DD2-HDAC6 binding site with the lowest binding free energy, the same binding mode is maintained along the 100-ns-long MD simulations. Overall, our results provide structural information about the molecular flexibility of apo and holo DD2-HDAC6 states as well as insight of the map of interactions between DD2-HDAC6 and five well-known DD2-HDAC6 inhibitors allowing structural details to guide the drug design. Finally, we highlight the importance of combining different theoretical approaches to provide suitable structural models for structure-based drug design.

  17. [Dynamics of electron-conformational transitions in proteins and physical mechanisms of biomacromolecule function].

    Science.gov (United States)

    Shaĭtan, K V

    1992-01-01

    The proteins can be considered as a microheterogeneous structured media possessing memory and feedback properties. The conformational energy surface depends on the chemical states of protein groups. Conformational motions are local diffusion with relaxation times much longer than vibrational relaxation times in condensed media. Owing to the hierarchy of relaxation times chemical reaction rates depend on conformation parametrically. Regulation of functional activity by conformational mobility is accomplished via transmission of information in the form of changes in the distribution functions of separate groups along the conformational substates. The interpretation of drastic effects on conformational mobility needs super-stochastic approaches. A possible mechanism of sharp conformational change are discussed in terms of the catastrophe theory.

  18. Molecular dynamics analysis of conformational change of paramyxovirus F protein during the initial steps of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Garcia, Fernando; Mendieta-Moreno, Jesus Ignacio; Mendieta, Jesus [Centro de Biologia Molecular ' Severo Ochoa' (CSIC/UAM), C/ Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid (Spain); Biomol-Informatics SL, Parque Cientifico de Madrid, C/ Faraday, 7, Cantoblanco, 28049 Madrid (Spain); Gomez-Puertas, Paulino, E-mail: pagomez@cbm.uam.es [Centro de Biologia Molecular ' Severo Ochoa' (CSIC/UAM), C/ Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid (Spain)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Initial conformational change of paramyxovirus F protein is caused only by mechanical forces. Black-Right-Pointing-Pointer HRA region undergoes a structural change from a beta + alpha conformation to an extended coil and then to an all-alpha conformation. Black-Right-Pointing-Pointer HRS domains of F protein form three single {alpha}-helices prior to generation of the coiled coil. -- Abstract: The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F protein) present in the virus envelope, which undergoes a dramatic conformational change during the process. Unlike hemagglutinin in orthomyxovirus, this change is not mediated by an alteration of environmental pH, and its cause remains unknown. Steered molecular dynamics analysis leads us to suggest that the conformational modification is mediated only by stretching mechanical forces once the transmembrane fusion peptide of the protein is anchored to the cell membrane. Such elongating forces will generate major secondary structure rearrangement in the heptad repeat A region of the F protein; from {beta}-sheet conformation to an elongated coil and then spontaneously to an {alpha}-helix. In addition, it is proposed that the heptad repeat A region adopts a final three-helix coiled coil and that this structure appears after the formation of individual helices in each monomer.

  19. Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain.

    Science.gov (United States)

    Selwa, Edithe; Huynh, Tru; Ciccotti, Giovanni; Maragliano, Luca; Malliavin, Thérèse E

    2014-10-01

    The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis is activated by interaction with calmodulin (CaM), resulting in cAMP overproduction in the infected cell. In the X-ray crystallographic structure of the complex between AC and the C terminal lobe of CaM, the toxin displays a markedly elongated shape. As for the structure of the isolated protein, experimental results support the hypothesis that more globular conformations are sampled, but information at atomic resolution is still lacking. Here, we use temperature-accelerated molecular dynamics (TAMD) simulations to generate putative all-atom models of globular conformations sampled by CaM-free AC. As collective variables, we use centers of mass coordinates of groups of residues selected from the analysis of standard molecular dynamics (MD) simulations. Results show that TAMD allows extended conformational sampling and generates AC conformations that are more globular than in the complexed state. These structures are then refined via energy minimization and further unrestrained MD simulations to optimize inter-domain packing interactions, thus resulting in the identification of a set of hydrogen bonds present in the globular conformations.

  20. Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer.

    Directory of Open Access Journals (Sweden)

    Giulia Morra

    2009-03-01

    Full Text Available Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine "hot spots" involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a "conformational selection model" of the Hsp90 mechanism, whereby the protein may

  1. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Laurence, Ted Alfred

    2002-07-30

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  2. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Laurence, Ted Alfred [Univ. of California, Berkeley, CA (United States)

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  3. Conformational Study of 8-C-glucosyl-prunetin by Dynamic NMR Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    By means of variable temperature NMR spectra, conformation of 8-C-glucosyl prunetin,isolated from the leaves of Dalbergia hainanensis (Leguminosae), was studied. The restricted rotation around the C (sp3)-C (sp2) bond in the C-glucosides isoflavonoid results in two main conformers (syn and anti). With the help of MM calculation, the preferred conformation A has H-I" gauche to the 7-OCH3. The barrier to rotation was 18.1 kcal/mol. This result agrees with the calculated value 16.2 kcal/mol of free energy of activation for the interconversion between the conformers.

  4. Conformational Study of 8—C—glucosyl—prunetin by Dynamic NMR Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    PeiChengZHANG; YingHongWANG; 等

    2002-01-01

    By means of variable temperature NMR spectra,conformation of 8-C-glucosyl prunetin, isolated from the leaves of Dalbergia hainanensis (Leguminosae), was studied. The restricted rotation around the C(sp3)-C(sp2) bond in the C-glucosides isoflavonoid results in two main conformers (syn and anti). With the help of MM calculation, the preferred conformation A has H-1″ gauche to the 7-OCH3. The barrier to rotation was 18.1 kcal/mol. This result agrees with the calculated value 16.2 kcal/mol of free energy of activation for the interconversion between the conformers.

  5. On dynamical realizations of l-conformal Galilei and Newton–Hooke algebras

    Directory of Open Access Journals (Sweden)

    Anton Galajinsky

    2015-07-01

    Full Text Available In two recent papers (Aizawa et al., 2013 [15] and (Aizawa et al., 2015 [16], representation theory of the centrally extended l-conformal Galilei algebra with half-integer l has been applied so as to construct second order differential equations exhibiting the corresponding group as kinematical symmetry. It was suggested to treat them as the Schrödinger equations which involve Hamiltonians describing dynamical systems without higher derivatives. The Hamiltonians possess two unusual features, however. First, they involve the standard kinetic term only for one degree of freedom, while the remaining variables provide contributions linear in momenta. This is typical for Ostrogradsky's canonical approach to the description of higher derivative systems. Second, the Hamiltonian in the second paper is not Hermitian in the conventional sense. In this work, we study the classical limit of the quantum Hamiltonians and demonstrate that the first of them is equivalent to the Hamiltonian describing free higher derivative nonrelativistic particles, while the second can be linked to the Pais–Uhlenbeck oscillator whose frequencies form the arithmetic sequence ωk=(2k−1, k=1,…,n. We also confront the higher derivative models with a genuine second order system constructed in our recent work (Galajinsky and Masterov, 2013 [5] which is discussed in detail for l=32.

  6. Adiabatic bias molecular dynamics: A method to navigate the conformational space of complex molecular systems

    Science.gov (United States)

    Marchi, Massimo; Ballone, Pietro

    1999-02-01

    This study deals with a novel molecular simulation technique, named adiabatic bias molecular dynamics (MD), which provides a simple and reasonably inexpensive route to generate MD trajectories joining points in conformational space separated by activation barriers. Because of the judicious way the biasing potential is updated during the MD runs, the technique allows with some additional effort the computation of the free energy change experienced during the trajectory. The adiabatic bias method has been applied to a nontrivial problem: The unfolding of an atomistic model of lysozyme. Here, the radius of gyration (Rg) was used as a convenient reaction coordinate. For changes in Rg between 19.7 and 28 Å, we observe a net loss of the native tertiary structure of lysozyme. At the same time, secondary structure elements such as α-helices are retained although some of the original order is diminished. The calculated free energy profile for the unfolding transition shows a monotonous increase with Rg and depends crucially on the nonbonded cutoff used in the potential model.

  7. Probing conformational stability and dynamics of erythroid and nonerythroid spectrin: effects of urea and guanidine hydrochloride.

    Directory of Open Access Journals (Sweden)

    Malay Patra

    Full Text Available We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl. Fluorescence and circular dichroism (CD spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS. Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGuH20 for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from.

  8. Probing Conformational Stability and Dynamics of Erythroid and Nonerythroid Spectrin: Effects of Urea and Guanidine Hydrochloride

    Science.gov (United States)

    Patra, Malay; Mukhopadhyay, Chaitali; Chakrabarti, Abhijit

    2015-01-01

    We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl). Fluorescence and circular dichroism (CD) spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS). Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M) hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGuH20) for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from. PMID:25617632

  9. On dynamical realizations of l-conformal Galilei and Newton-Hooke algebras

    Science.gov (United States)

    Galajinsky, Anton; Masterov, Ivan

    2015-07-01

    In two recent papers (Aizawa et al., 2013 [15]) and (Aizawa et al., 2015 [16]), representation theory of the centrally extended l-conformal Galilei algebra with half-integer l has been applied so as to construct second order differential equations exhibiting the corresponding group as kinematical symmetry. It was suggested to treat them as the Schrödinger equations which involve Hamiltonians describing dynamical systems without higher derivatives. The Hamiltonians possess two unusual features, however. First, they involve the standard kinetic term only for one degree of freedom, while the remaining variables provide contributions linear in momenta. This is typical for Ostrogradsky's canonical approach to the description of higher derivative systems. Second, the Hamiltonian in the second paper is not Hermitian in the conventional sense. In this work, we study the classical limit of the quantum Hamiltonians and demonstrate that the first of them is equivalent to the Hamiltonian describing free higher derivative nonrelativistic particles, while the second can be linked to the Pais-Uhlenbeck oscillator whose frequencies form the arithmetic sequence ωk = (2 k - 1), k = 1, …, n. We also confront the higher derivative models with a genuine second order system constructed in our recent work (Galajinsky and Masterov, 2013 [5]) which is discussed in detail for l =3/2.

  10. Conformational dynamics and aggregation behavior of piezoelectric diphenylalanine peptides in an external electric field.

    Science.gov (United States)

    Kelly, Catherine M; Northey, Thomas; Ryan, Kate; Brooks, Bernard R; Kholkin, Andrei L; Rodriguez, Brian J; Buchete, Nicolae-Viorel

    2015-01-01

    Aromatic peptides including diphenylalanine (FF) have the capacity to self-assemble into ordered, biocompatible nanostructures with piezoelectric properties relevant to a variety of biomedical applications. Electric fields are commonly applied to align FF nanotubes, yet little is known about the effect of the electric field on the assembly process. Using all-atom molecular dynamics with explicit water molecules, we examine the response of FF monomers to the application of a constant external electric field over a range of intensities. We probe the aggregation mechanism of FF peptides, and find that the presence of even relatively weak fields can accelerate ordered aggregation, primarily by facilitating the alignment of individual molecular dipole moments. This is modulated by the conformational response of individual FF peptides (e.g., backbone stretching) and by the cooperative alignment of neighboring FF and water molecules. These observations may facilitate future studies on the controlled formation of nanostructured aggregates of piezoelectric peptides and the understanding of their electro-mechanical properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Comparison of Chain Conformation of Poly(vinyl alcohol) in Solutions and Melts from Quantum Chemistry Based Molecular Dynamics Simulations

    Science.gov (United States)

    Jaffe, Richard; Han, Jie; Matsuda, Tsunetoshi; Yoon, Do; Langhoff, Stephen R. (Technical Monitor)

    1997-01-01

    Confirmations of 2,4-dihydroxypentane (DHP), a model molecule for poly(vinyl alcohol), have been studied by quantum chemistry (QC) calculations and molecular dynamics (MD) simulations. QC calculations at the 6-311G MP2 level show the meso tt conformer to be lowest in energy followed by the racemic tg, due to intramolecular hydrogen bond between the hydroxy groups. The Dreiding force field has been modified to reproduce the QC conformer energies for DHP. MD simulations using this force field have been carried out for DHP molecules in the gas phase, melt, and CHCl3 and water solutions. Extensive intramolecular hydrogen bonding is observed for the gas phase and CHCl3 solution, but not for the melt or aqueous solution, Such a condensed phase effect due to intermolecular interactions results in a drastic change in chain conformations, in agreement with experiments.

  12. Semiempirical and ab initio calculations versus dynamic NMR on conformational analysis of cyclohexyl-N,N-dimethylcarbamate

    Directory of Open Access Journals (Sweden)

    Basso Ernani A.

    2001-01-01

    Full Text Available Axial-equatorial conformational proportions for cyclohexyl-N,N-dimethyl carbamate have been measured, for the first time, by the Eliel method, ¹H and 13C dynamic nuclear magnetic resonance (DNMR. The results were compared against those determined by theoretical calculations. By the Eliel method at least five experimentally independent measureables were used in CCl4, CDCl3 and CD3CN. The ¹H and 13C low temperature experiments were performed in CF2Br2/CD2Cl2 . Semiempirical methods MNDO, AM1 and PM3 and ab initio molecular orbital calculations at the HF/STO-3G and HF/6-31G(d,p levels have been performed on the axial and equatorial conformers populations. All applied methods correctly predict the equatorial conformer preference over the axial one. The resulting equatorial preferences determined by NMR data and theoretical calculations are in good agreement.

  13. Molecular dynamics simulation reveals conformational switching of water-mediated uracil-cytosine base-pairs in an RNA duplex.

    Science.gov (United States)

    Schneider, C; Brandl, M; Sühnel, J

    2001-01-26

    A 4 ns molecular dynamics simulation of an RNA duplex (r-GGACUUCGGUCC)(2 )in solution with Na+ and Cl- as counterions was performed. The X-ray structure of this duplex includes two water-mediated uracil-cytosine pairs. In contrast to the other base-pairs in the duplex the water-mediated pairs switch between different conformations. One conformation corresponds to the geometry of the water-mediated UC pairs in the duplex X-ray structure with water acting both as hydrogen-bond donor and acceptor. Another conformation is close to that of a water-mediated UC base-pair found in the X-ray structure of the 23 S rRNA sarcin/ricin domain. In this case the oxygen of the water molecule is linked to two-base donor sites. For a very short time also a direct UC base-pair and a further conformation that is similar to the one found in the RNA duplex structure but exhibits an increased H3(U)...N3(C) distance is observed. Water molecules with unusually long residence times are involved in the water-mediated conformations. These results indicate that the dynamic behaviour of the water-mediated UC base-pairs differs from that of the duplex Watson-Crick and non-canonical guanine-uracil pairs with two or three direct hydrogen bonds. The conformational variability and increased flexibility has to be taken into account when considering these base-pairs as RNA building blocks and as recognition motifs. Copyright 2001 Academic Press.

  14. Arc Interference Behavior during Twin Wire Gas Metal Arc Welding Process

    Directory of Open Access Journals (Sweden)

    Dingjian Ye

    2013-01-01

    Full Text Available In order to study arc interference behavior during twin wire gas metal arc welding process, the synchronous acquisition system has been established to acquire instantaneous information of arc profile including dynamic arc length variation as well as relative voltage and current signals. The results show that after trailing arc (T-arc is added to the middle arc (M-arc in a stable welding process, the current of M arc remains unchanged while the agitation increases; the voltage of M arc has an obvious increase; the shape of M arc changes, with increasing width, length, and area; the transfer frequency of M arc droplet increases and the droplet itself becomes smaller. The wire extension length of twin arc turns out to be shorter than that of single arc welding.

  15. Molecular dynamics simulation study of conformational changes of transcription factor TFIIS during RNA polymerase II transcriptional arrest and reactivation.

    Directory of Open Access Journals (Sweden)

    Changsun Eun

    Full Text Available Transcription factor IIS (TFIIS is a protein known for catalyzing the cleavage reaction of the 3'-end of backtracked RNA transcript, allowing RNA polymerase II (Pol II to reactivate the transcription process from the arrested state. Recent structural studies have provided a molecular basis of protein-protein interaction between TFIIS and Pol II. However, the detailed dynamic conformational changes of TFIIS upon binding to Pol II and the related thermodynamic information are largely unknown. Here we use computational approaches to investigate the conformational space of TFIIS in the Pol II-bound and Pol II-free (unbound states. Our results reveal two distinct conformations of TFIIS: the closed and the open forms. The closed form is dominant in the Pol II-free (unbound state of TFIIS, whereas the open form is favorable in the Pol II-bound state. Furthermore, we discuss the free energy difference involved in the conformational changes between the two forms in the presence or absence of Pol II. Additionally, our analysis indicates that hydrophobic interactions and the protein-protein interactions between TFIIS and Pol II are crucial for inducing the conformational changes of TFIIS. Our results provide novel insights into the functional interplay between Pol II and TFIIS as well as mechanism of reactivation of Pol II transcription by TFIIS.

  16. Structural dynamics of the monoamine transporter homologue LeuT from accelerated conformational sampling and channel analysis

    Science.gov (United States)

    Thomas, James R.; Gedeon, Patrick C.; Madura, Jeffry D.

    2014-01-01

    The bacterial leucine transporter LeuT retains significant secondary structure similarities to the human monoamine transporters (MAT) such as the dopamine and serotonin reuptake proteins. The primary method of computational study of the MATs has been through the use of the crystallized LeuT structure. Different conformations of LeuT can give insight into mechanistic details of the MAT family. A conformational sampling performed through accelerated molecular dynamics (aMD) simulations testing different combinations of the leucine substrate and bound sodium ions revealed seven distinct conformational clusters. Further analysis has been performed to target salt-bridge residues R30–D404, Y108–F253, and R5–D369 and transmembrane domains on both the seven isolated structures and the total trajectories. In addition, solvent accessibility of LeuT and its substrate binding pockets has been analyzed using a program for calculating channel radii. Occupation of the Na2 site stabilizes the outward conformation and should bind to the open outward conformation before the leucine and Na1 sodium while two possible pathways were found to be available for intracellular transport. PMID:24753369

  17. Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.

    Science.gov (United States)

    Thomas, James R; Gedeon, Patrick C; Madura, Jeffry D

    2014-10-01

    The bacterial leucine transporter LeuT retains significant secondary structure similarities to the human monoamine transporters (MAT) such as the dopamine and serotonin reuptake proteins. The primary method of computational study of the MATs has been through the use of the crystallized LeuT structure. Different conformations of LeuT can give insight into mechanistic details of the MAT family. A conformational sampling performed through accelerated molecular dynamics simulations testing different combinations of the leucine substrate and bound sodium ions revealed seven distinct conformational clusters. Further analysis has been performed to target salt-bridge residues R30-D404, Y108-F253, and R5-D369 and transmembrane domains on both the seven isolated structures and the total trajectories. In addition, solvent accessibility of LeuT and its substrate binding pockets has been analyzed using a program for calculating channel radii. Occupation of the Na2 site stabilizes the outward conformation and should bind to the open outward conformation before the leucine and Na1 sodium while two possible pathways were found to be available for intracellular transport.

  18. Another way to view the chain conformation broadening of the line-width distribution measured in dynamic light scattering

    Institute of Scientific and Technical Information of China (English)

    吴奇; 牛爱珍

    1999-01-01

    In dynamic laser light scattering (LLS), for a given polydisperse sample, a line-width distribution G(Γ) or the translational diffusion coefficient distribution G(D) can be obtained from the measured time correlation function. For rigid colloid particles, G(Γ) can be directly related to the hydrodynamic size distribution. However, for flexible polymer chains, G(Γ) depends not only on the chain length distribution, but also on the relaxation of the chain conformation; that is, even for a monodisperse polymer sample there still exists a chain conformation distribution. If the time scale of the chain conformation relaxation is comparable to that of the translational diffusion, such as in the case of a very long polymer chain, the conformation relaxation might lead to an additional broadening in G (Γ). This "conformation broadening" has been directly observed for the first time by comparing two G(Γ) s obtained from a poly(N-isopropyl-acrylamide) solution at~25℃ and~32℃ at which the solution is ther

  19. Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering.

    Science.gov (United States)

    Wall, Michael E; Van Benschoten, Andrew H; Sauter, Nicholas K; Adams, Paul D; Fraser, James S; Terwilliger, Thomas C

    2014-12-16

    X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculations of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. Decomposition of the MD model into protein and solvent components indicates that protein-solvent interactions contribute substantially to the overall diffuse intensity. We conclude that diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.

  20. MODELING PARAMETERS OF ARC OF ELECTRIC ARC FURNACE

    Directory of Open Access Journals (Sweden)

    R.N. Khrestin

    2015-08-01

    Full Text Available Purpose. The aim is to build a mathematical model of the electric arc of arc furnace (EAF. The model should clearly show the relationship between the main parameters of the arc. These parameters determine the properties of the arc and the possibility of optimization of melting mode. Methodology. We have built a fairly simple model of the arc, which satisfies the above requirements. The model is designed for the analysis of electromagnetic processes arc of varying length. We have compared the results obtained when testing the model with the results obtained on actual furnaces. Results. During melting in real chipboard under the influence of changes in temperature changes its properties arc plasma. The proposed model takes into account these changes. Adjusting the length of the arc is the main way to regulate the mode of smelting chipboard. The arc length is controlled by the movement of the drive electrode. The model reflects the dynamic changes in the parameters of the arc when changing her length. We got the dynamic current-voltage characteristics (CVC of the arc for the different stages of melting. We got the arc voltage waveform and identified criteria by which possible identified stage of smelting. Originality. In contrast to the previously known models, this model clearly shows the relationship between the main parameters of the arc EAF: arc voltage Ud, amperage arc id and length arc d. Comparison of the simulation results and experimental data obtained from real particleboard showed the adequacy of the constructed model. It was found that character of change of magnitude Md, helps determine the stage of melting. Practical value. It turned out that the model can be used to simulate smelting in EAF any capacity. Thus, when designing the system of control mechanism for moving the electrode, the model takes into account changes in the parameters of the arc and it can significantly reduce electrode material consumption and energy consumption

  1. Impact of sulfation pattern on the conformation and dynamics of sulfated fucan oligosaccharides as revealed by NMR and MD.

    Science.gov (United States)

    Queiroz, Ismael N L; Wang, Xiaocong; Glushka, John N; Santos, Gustavo R C; Valente, Ana P; Prestegard, James H; Woods, Robert J; Mourão, Paulo A S; Pomin, Vitor H

    2015-05-01

    Sulfated fucans from sea urchin egg jelly express well-defined chemical structures that vary with species. This species specificity regulates the sperm acrosome reaction, a critical step to assure intra-specific fertilization. In addition, these polysaccharides are involved in other biological activities such as anticoagulation. Although sulfation patterns are relevant to the levels of response in both activities, conformation and dynamics of these glycans are also contributing factors. However, data about these features of sulfated fucans are very rare. To address this, we have employed nuclear magnetic resonance experiments combined with molecular dynamics on structurally defined oligosaccharides derived from two sulfated fucans. The results have indicated that the oligosaccharides are flexible in solution. Ring conformation of their composing units displays just the (1)C4 chair configuration. In a particular octasaccharide, composed of two tetrasaccharide sequences, inter-residual hydrogen bonds play a role to decrease dynamics in these repeating units. Conversely, the linking disaccharide [-3)-α-L-Fucp-2(OSO3(-))-(1-3)-α-L-Fucp-4(OCO3(-))-(1-] located right between the two tetrasaccharide units has amplified motions suggested to be promoted by electrostatic repulsion of sulfates on opposite sides of the central glycosidic bond. This conjunction of information about conformation and dynamics of sulfated fucan oligosaccharides provides new insights to explain how these glycans behave free in solution and influenced by sulfation patterns. It may also serve for future studies concerning structure-function relationship of sulfated fucans, especially those involving sea urchin fertilization and anticoagulation.

  2. Is high–dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors?

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Bo; Yang, Yong, E-mail: yangy2@upmc.edu; Li, Xiang; Li, Tianfang; Heron, Dwight E.; Saiful Huq, M.

    2015-04-01

    In linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT), circular cone(s) or conformal arc(s) are conventionally used to treat intracranial lesions. However, when the target is in close proximity to critical structures, it is frequently quite challenging to generate a quality plan using these techniques. In this study, we investigated the dosimetric characteristics of using high–dose rate RapidArc (RA) technique for radiosurgical treatment of intracranial lesions. A total of 10 intracranial SRS/SRT cases previously planned using dynamic conformal arc (DCA) or cone-based techniques have been included in this study. For each case, 3 treatment plans were generated: (1) a DCA plan with multiple noncoplanar arcs, (2) a high–dose rate RA plan with arcs oriented the same as DCA (multiple-arc RA), and 3) a high–dose rate RA plan with a single coplanar arc (single-arc RA). All treatment plans were generated under the same prescription and similar critical structure dose limits. Plan quality for different plans was evaluated by comparing various dosimetric parameters such as target coverage, conformity index (CI), homogeneity index (HI), critical structures, and normal brain tissue doses as well as beam delivery time. With similar critical structure sparing, high–dose rate RA plans can achieve much better target coverage, dose conformity, and dose homogeneity than the DCA plans can. Plan quality indices CI and HI, for the DCA, multiple-arc RA, and single-arc RA techniques, were measured as 1.67 ± 0.39, 1.32 ± 0.28, and 1.38 ± 0.30 and 1.24 ± 0.11, 1.10 ± 0.04, and 1.12 ± 0.07, respectively. Normal brain tissue dose (V{sub 12} {sub Gy}) was found to be similar for DCA and multiple-arc RA plans but much larger for the single-arc RA plans. Beam delivery was similar for DCA and multiple-arc RA plans but shorter with single-arc RA plans. Multiple-arc RA SRS/SRT can provide better treatment plans than conventional DCA plans, especially for complex cases.

  3. NMR-based conformation and dynamics of a tetrasaccharide-repeating sulfated fucan substituted by different counterions.

    Science.gov (United States)

    Soares, Paulo A G; Queiroz, Ismael N L; Santos, Gustavo R C; Mourão, Paulo A S; Pomin, Vitor H

    2016-11-01

    The sulfated fucan from the sea urchin Lytechinus variegatus is composed of the repetitive sequence [-3)-α-l-Fucp-4( OSO3-)-(1-3)-α-l-Fucp-2,4-di( OSO3-)-(1-3)-α-l-Fucp-2( OSO3-)-(1-3)-α-l-Fucp-2( OSO3-)-(1-]n . Conformation (of rings and chains) and dynamics of this tetrasaccharide-repeating sulfated fucan substituted by Na(+) , Ca(2+) , and Li(+) as counterions have been examined through experiments of liquid-state nuclear magnetic resonance spectroscopy. Scalar coupling and nuclear Overhauser effect (NOE)-based data have confirmed that all composing units occur as (1) C4 chair conformer regardless of the cation type, unit position within the repeating sequence, and sulfation type. Chain conformation determined by NOE signal pattern assisted by molecular modeling for a theoretical octasaccharide has shown a similar linear 3D structure for the three differently substituted forms. Data derived from spin-relaxation measurements have indicated a contribution of counterion type to dynamics. The calcium-based preparation has shown the highest mobility while the sodiated one showed the lowest mobility. The set of results from this work suggests that counterion type can affect the physicochemical properties of the structurally well-defined sulfated fucan. The counterion effect seems to impact more on the structural mobility than on average conformation of the studied sulfated glycan in solution.

  4. Conformational Plasticity in Glycomimetics: Fluorocarbamethyl-L-idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings.

    Science.gov (United States)

    Unione, Luca; Xu, Bixue; Díaz, Dolores; Martín-Santamaría, Sonsoles; Poveda, Ana; Sardinha, João; Rauter, Amelia Pilar; Blériot, Yves; Zhang, Yongmin; Cañada, F Javier; Sollogoub, Matthieu; Jiménez-Barbero, Jesus

    2015-07-13

    Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L-iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free-energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine-containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose- and glucose-like rings. We have used low-temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose-like rings. Under these conditions, the exchange rate becomes slow in the (19) F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of (19) F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.

  5. The dosimetric impact of inversely optimized arc radiotherapy plan modulation for real-time dynamic MLC tracking delivery

    DEFF Research Database (Denmark)

    Falk, Marianne; Larsson, Tobias; Keall, Paul

    2012-01-01

    -to-peak displacement of 2 cm and a cycle time of 6 s. The delivery was adjusted to the target motion using MLC tracking, guided in real-time by an infrared optical system. The dosimetric results were evaluated using gamma index evaluation with static target measurements as reference. Results: The plan quality......Purpose: Real-time dynamic multileaf collimator (MLC) tracking for management of intrafraction tumor motion can be challenging for highly modulated beams, as the leaves need to travel far to adjust for target motion perpendicular to the leaf travel direction. The plan modulation can be reduced...... on the dosimetric accuracy of MLC tracking delivery. Specifically, the possibility of predicting the accuracy of MLC tracking delivery based on the plan modulation was investigated. Methods: Inversely optimized arc radiotherapy plans were created on CT-data of three lung cancer patients. For each case, five plans...

  6. The EF loop in green proteorhodopsin affects conformation and photocycle dynamics.

    Science.gov (United States)

    Mehler, Michaela; Scholz, Frank; Ullrich, Sandra J; Mao, Jiafei; Braun, Markus; Brown, Lynda J; Brown, Richard C D; Fiedler, Sarah A; Becker-Baldus, Johanna; Wachtveitl, Josef; Glaubitz, Clemens

    2013-07-16

    The proteorhodopsin family consists of retinal proteins of marine bacterial origin with optical properties adjusted to their local environments. For green proteorhodopsin, a highly specific mutation in the EF loop, A178R, has been found to cause a surprisingly large redshift of 20 nm despite its distance from the chromophore. Here, we analyze structural and functional consequences of this EF loop mutation by time-resolved optical spectroscopy and solid-state NMR. We found that the primary photoreaction and the formation of the K-like photo intermediate is almost pH-independent and slower compared to the wild-type, whereas the decay of the K-intermediate is accelerated, suggesting structural changes within the counterion complex upon mutation. The photocycle is significantly elongated mainly due to an enlarged lifetime of late photo intermediates. Multidimensional MAS-NMR reveals mutation-induced chemical shift changes propagating from the EF loop to the chromophore binding pocket, whereas dynamic nuclear polarization-enhanced (13)C-double quantum MAS-NMR has been used to probe directly the retinylidene conformation. Our data show a modified interaction network between chromophore, Schiff base, and counterion complex explaining the altered optical and kinetic properties. In particular, the mutation-induced distorted structure in the EF loop weakens interactions, which help reorienting helix F during the reprotonation step explaining the slower photocycle. These data lead to the conclusion that the EF loop plays an important role in proton uptake from the cytoplasm but our data also reveal a clear interaction pathway between the EF loop and retinal binding pocket, which might be an evolutionary conserved communication pathway in retinal proteins.

  7. A note on conformally compactified connection dynamics tailored for anti-de Sitter space

    Science.gov (United States)

    Bodendorfer, N.

    2016-12-01

    A framework conceptually based on the conformal techniques employed to study the structure of the gravitational field at infinity is set up in the context of loop quantum gravity to describe asymptotically anti-de Sitter quantum spacetimes. A conformal compactification of the spatial slice is performed, which, in terms of the rescaled metric, has now finite volume, and can thus be conveniently described by spin networks states. The conformal factor used is a physical scalar field, which has the necessary asymptotics for many asymptotically AdS black hole solutions.

  8. Conformational dynamics of ligand-dependent alternating access in LeuT

    OpenAIRE

    Kazmier, Kelli; Sharma, Shruti; Quick, Matthias; Islam, Shahidul M.; Roux, Benoit; Weinstein, Harel; Javitch, Jonathan A.; Mchaourab, Hassane S.

    2014-01-01

    The leucine transporter (LeuT) from Aquifex aeolicus is a bacterial homolog of neurotransmitter:sodium symporters (NSS) that catalyze reuptake of neurotransmitters at the synapse. Crystal structures of wild type (WT) and mutants of LeuT have been interpreted as conformational states in the coupled transport cycle. However, the mechanistic identities inferred from these structures have not been validated and the ligand-dependent conformational equilibrium of LeuT has not been defined. Here, we...

  9. On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm.

    Science.gov (United States)

    Marcos, Enrique; Crehuet, Ramon; Bahar, Ivet

    2010-04-08

    N-acetyl-L-glutamate kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence-->structure-->dynamics-->function.

  10. Large-Scale Conformational Dynamics Control H5N1 Influenza Polymerase PB2 Binding to Importin α.

    Science.gov (United States)

    Delaforge, Elise; Milles, Sigrid; Bouvignies, Guillaume; Bouvier, Denis; Boivin, Stephane; Salvi, Nicola; Maurin, Damien; Martel, Anne; Round, Adam; Lemke, Edward A; Jensen, Malene Ringkjøbing; Hart, Darren J; Blackledge, Martin

    2015-12-09

    Influenza A RNA polymerase complex is formed from three components, PA, PB1, and PB2. PB2 is independently imported into the nucleus prior to polymerase reconstitution. All crystallographic structures of the PB2 C-terminus (residues 536-759) reveal two globular domains, 627 and NLS, that form a tightly packed heterodimer. The molecular basis of the affinity of 627-NLS for importins remained unclear from these structures, apparently requiring large-scale conformational changes prior to importin binding. Using a combination of solution-state NMR, small-angle neutron scattering, small-angle X-ray scattering (SAXS), and Förster resonance energy transfer (FRET), we show that 627-NLS populates a temperature-dependent dynamic equilibrium between closed and open states. The closed state is stabilized by a tripartite salt bridge involving the 627-NLS interface and the linker, that becomes flexible in the open state, with 627 and NLS dislocating into a highly dynamic ensemble. Activation enthalpies and entropies associated with the rupture of this interface were derived from simultaneous analysis of temperature-dependent chemical exchange saturation transfer measurements, revealing a strong temperature dependence of both open-state population and exchange rate. Single-molecule FRET and SAXS demonstrate that only the open-form is capable of binding to importin α and that, upon binding, the 627 domain samples a dynamic conformational equilibrium in the vicinity of the C-terminus of importin α. This intrinsic large-scale conformational flexibility therefore enables 627-NLS to bind importin through conformational selection from a temperature-dependent equilibrium comprising both functional forms of the protein.

  11. Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex.

    Science.gov (United States)

    Damian, Marjorie; Mary, Sophie; Maingot, Mathieu; M'Kadmi, Céline; Gagne, Didier; Leyris, Jean-Philippe; Denoyelle, Séverine; Gaibelet, Gérald; Gavara, Laurent; Garcia de Souza Costa, Mauricio; Perahia, David; Trinquet, Eric; Mouillac, Bernard; Galandrin, Ségolène; Galès, Céline; Fehrentz, Jean-Alain; Floquet, Nicolas; Martinez, Jean; Marie, Jacky; Banères, Jean-Louis

    2015-02-03

    How G protein-coupled receptor conformational dynamics control G protein coupling to trigger signaling is a key but still open question. We addressed this question with a model system composed of the purified ghrelin receptor assembled into lipid discs. Combining receptor labeling through genetic incorporation of unnatural amino acids, lanthanide resonance energy transfer, and normal mode analyses, we directly demonstrate the occurrence of two distinct receptor:Gq assemblies with different geometries whose relative populations parallel the activation state of the receptor. The first of these assemblies is a preassembled complex with the receptor in its basal conformation. This complex is specific of Gq and is not observed with Gi. The second one is an active assembly in which the receptor in its active conformation triggers G protein activation. The active complex is present even in the absence of agonist, in a direct relationship with the high constitutive activity of the ghrelin receptor. These data provide direct evidence of a mechanism for ghrelin receptor-mediated Gq signaling in which transition of the receptor from an inactive to an active conformation is accompanied by a rearrangement of a preassembled receptor:G protein complex, ultimately leading to G protein activation and signaling.

  12. Mantle Dynamics of Australia-Banda Arc Collision as Inferred from Shear Wave Splitting Analysis of Teleseismic and Local Slab Events

    Science.gov (United States)

    Harris, C. W.; Miller, M. S.; O'Driscoll, L.; Porritt, R. W.; Roosmawati, N.; Widiyantoro, S.

    2015-12-01

    Arc-continent collision is an important factor in continent building, orogensis, and ocean closure, yet the details associated with it are not fully understood. East-Timor and the Nusa Tenggara Timur region of Indonesia provide a unique setting to study a young arc-continent collision (~8 Ma) and incipient orogenesis. The NSF funded Banda Arc project affords a rare opportunity to investigate unconstrained processes such as active continental subduction and slab rupture beneath a regional deployment of broadband seismometers. We use data from 35 broadband sensors to analyze seismic anisotropy through measuring shear wave splitting. These stations span the roughly east-west transition from normal oceanic subduction at the Sunda Arc to collision at the Banda Arc, and cross areas associated with back-arc thrusting, arc volcanism, extinct volcanism and a rapidly exhuming forearc. Thirty of the sensors used in the analysis are temporary stations installed by our research team in 2014 and will remain in the field until 2016 or later. The remaining stations are part of the open-access GFZ GEOFON global seismic network. We present preliminary shear wave splitting results for teleseismic (*KS core phases) and local (direct S phase) arrivals in order to inspect the sub-slab mantle and the supra-slab mantle wedge for anisotropic patterns related to olivine flow fabric. These results can be used to assess regional strain linked to ongoing collision and may elucidate any slab tearing that has resulted from the (partial) subduction of buoyant continental material of Australian affinity. Presently, we observe a trend of primarily trench-parallel sub-slab fast polarization directions and perhaps more complicated anisotropy in the mantle wedge. Relative to the trench, there appears to be more spatial variation in fast axis orientation for direct arrivals than teleseismic phases. We discuss how the interpretation of our initial results provides insight into the mantle dynamics of the

  13. Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance

    Directory of Open Access Journals (Sweden)

    Glantz-Gashai Y

    2017-06-01

    Full Text Available Yitav Glantz-Gashai,* Tomer Meirson,* Eli Reuveni, Abraham O Samson Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel *These authors contributed equally to this work Abstract: Myeloid cell leukemia-1 (Mcl-1 is often overexpressed in human cancer and is an important target for developing antineoplastic drugs. In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB ID 2MHS. The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA, molecular dynamics (MD, and nuclear magnetic resonance (NMR, respectively. The evaluated potential Mcl-1 ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer. The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors. Keywords: virtual screening, Mcl-1, molecular dynamics, NMR, normal modes

  14. Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations.

    Science.gov (United States)

    Wang, Beibei; Weng, Jingwei; Wang, Wenning

    2014-09-01

    Outer membrane protein TolC serves as an exit duct for exporting substances out of cell. The occluded periplasmic entrance of TolC is required to open for substrate transport, although the opening mechanism remains elusive. In this study, systematic molecular dynamics (MD) simulations for wild type TolC and six mutants were performed to explore the conformational dynamics of TolC. The periplasmic gate was shown to sample multiple conformational states with various degrees of gating opening. The gate opening was facilitated by all mutations except Y362F, which adopts an even more closed state than wild type TolC. The interprotomer salt-bridge R367-D153 is turned out to be crucial for periplasmic gate opening. The mutations that disrupt the interactions at the periplasmic tip may affect the stability of the trimeric assembly of TolC. Structural asymmetry of the periplasmic gate was observed to be opening size dependent. Asymmetric conformations are found in moderately opening states, while the most and the least opening states are often more symmetric. Finally, it is shown that lowering pH can remarkably stabilize the closed state of the periplasmic gate.

  15. Single-molecule diffusion and conformational dynamics by spatial integration of temporal fluctuations

    KAUST Repository

    Bayoumi, Maged Fouad

    2014-10-06

    Single-molecule localization and tracking has been used to translate spatiotemporal information of individual molecules to map their diffusion behaviours. However, accurate analysis of diffusion behaviours and including other parameters, such as the conformation and size of molecules, remain as limitations to the method. Here, we report a method that addresses the limitations of existing single-molecular localization methods. The method is based on temporal tracking of the cumulative area occupied by molecules. These temporal fluctuations are tied to molecular size, rates of diffusion and conformational changes. By analysing fluorescent nanospheres and double-stranded DNA molecules of different lengths and topological forms, we demonstrate that our cumulative-area method surpasses the conventional single-molecule localization method in terms of the accuracy of determined diffusion coefficients. Furthermore, the cumulative-area method provides conformational relaxation times of structurally flexible chains along with diffusion coefficients, which together are relevant to work in a wide spectrum of scientific fields.

  16. A unified conformal model for fundamental interactions without dynamical Higgs field

    CERN Document Server

    Pawlowski, M; Marek Pawlowski; Ryszard Raczka

    1994-01-01

    A Higgsless model for strong, electro-weak and gravitational interactions is proposed. This model is based on the local symmetry group SU(3)xSU(2)xU(1)xC where C is the local conformal symmetry group. The natural minimal conformally invariant form of total lagrangian is postulated. It contains all Standard Model fields and gravitational interaction. Using the unitary gauge and the conformal scale fixing conditions we can eliminate all four real components of the Higgs doublet in this model. However the masses of vector mesons, leptons and quarks are automatically generated and are given by the same formulas as in the conventional Standard Model. The gravitational sector is analyzed and it is shown that the model admits in the classical limit the Einsteinian form of gravitational interactions. No figures.

  17. Coupling between internal dynamics and rotational diffusion in the presence of exchange between discrete molecular conformations.

    Science.gov (United States)

    Ryabov, Yaroslav; Clore, G Marius; Schwieters, Charles D

    2012-01-21

    We present a general formalism for the computation of orientation correlation functions involving a molecular system undergoing rotational diffusion in the presence of transitions between discrete conformational states. In this formalism, there are no proscriptions on the time scales of conformational rearrangement relative to that for rotational diffusion, and the rotational diffusion tensors of the different states can be completely arbitrary. Although closed-form results are limited to the frequency domain, this is generally useful for many spectroscopic observables as the result allows the computation of the spectral density function. We specialize the results for the computation of the frequency-domain correlation function associated with the NMR relaxation.

  18. TU-CD-304-02: Planning and Delivery of Fully Dynamic Trajectory Modulated Arc Therapy On Pituitary Adenoma: Dosimetric Advantages Over Conventional Volumetric Modulated Arc Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liang, J; Kim, S [Department of Radiation Oncology, Virginia Commonwealth University, Virginia (United States); Hristov, D [Department of Radiation Oncology, Stanford University, CA (United States); Otto, K [Department of Physics, University of British Columbia, British Columbia (Canada)

    2015-06-15

    Purpose: To assess the potential benefit of trajectory modulated arc therapy (TMAT) for treatments of small benign intracranial tumor, pituitary adenoma. Methods: A TMAT planning platform that incorporates complex source motion trajectory involving synchronized gantry rotation with translational and rotational couch movement was used for the study. The platform couples an interactive trajectory generation tool with a VMAT algorithm that performs multi-resolution, progressive sampling MLC optimization on a user-designed trajectory. A continuous couch rotation of 160° angular span with ±20° mini gantry arcs was used to emulate a non-coplanar horizontal arc-like trajectory. Compared to conventional non-coplanar gantry arcs (60°-100° gantry rotation with couch kicks), TMAT limited the unnecessary low to medium dose spread in the anterior and posterior directions, where primary OARs (e.g., brainstem, optic chiasm, optic nerves, and lens) are in close proximity to the targeted pituitary tumor volume. For 5 standard fractionation pituitary adenoma cases (50.4Gy/28fractions), TMAT and non-coplanar VMAT plans were generated and compared under equivalent objectives/constraints. TMAT delivery was implemented and demonstrated on Varian TrueBeam via XML scripts. Results: Both techniques showed good target coverage while OARs were able to meet the constraints on QUANTEC guidelines. Notably, TMAT decreased the dose deposition in the anterior-to-posterior direction surrounding PTV. TMAT significantly reduced the mean doses on brainstem, optic nerves, eyes and lens by 47.29%±13.17%, 28.51%±8.68%, 80.82%±8.71% and 65.38%±19.99% compared with VMAT, all p≤0.01. Percentage reductions of maximum point dose in eyes and lens were 75.68%±10.30% and 70.72%±18.62% respectively for TMAT versus VMAT, all p≤0.01. A representative isocentric TMAT pituitary plan was delivered via an XML script with 200 control points and 282 MUs. Conclusion: Deliverable TMAT plans were achieved in

  19. Couplings between hierarchical conformational dynamics from multi-time correlation functions and two-dimensional lifetime spectra: Application to adenylate kinase.

    Science.gov (United States)

    Ono, Junichi; Takada, Shoji; Saito, Shinji

    2015-06-07

    An analytical method based on a three-time correlation function and the corresponding two-dimensional (2D) lifetime spectrum is developed to elucidate the time-dependent couplings between the multi-timescale (i.e., hierarchical) conformational dynamics in heterogeneous systems such as proteins. In analogy with 2D NMR, IR, electronic, and fluorescence spectroscopies, the waiting-time dependence of the off-diagonal peaks in the 2D lifetime spectra can provide a quantitative description of the dynamical correlations between the conformational motions with different lifetimes. The present method is applied to intrinsic conformational changes of substrate-free adenylate kinase (AKE) using long-time coarse-grained molecular dynamics simulations. It is found that the hierarchical conformational dynamics arise from the intra-domain structural transitions among conformational substates of AKE by analyzing the one-time correlation functions and one-dimensional lifetime spectra for the donor-acceptor distances corresponding to single-molecule Förster resonance energy transfer experiments with the use of the principal component analysis. In addition, the complicated waiting-time dependence of the off-diagonal peaks in the 2D lifetime spectra for the donor-acceptor distances is attributed to the fact that the time evolution of the couplings between the conformational dynamics depends upon both the spatial and temporal characters of the system. The present method is expected to shed light on the biological relationship among the structure, dynamics, and function.

  20. Periodic orbits and 10 cases of unbounded dynamics for one Hamiltonian system defined by the conformally coupled field

    Energy Technology Data Exchange (ETDEWEB)

    Starkov, Konstantin E., E-mail: kstarkov@ipn.mx

    2015-07-03

    In this paper we study invariant domains with unbounded dynamics for one cosmological Hamiltonian system which is formed by the conformally coupled field; this system was introduced by Maciejewski et al. (2007). We find a few groups of conditions imposed on parameters of this system for which all trajectories are unbounded in both of time directions. Further, we present a few groups of other conditions imposed on system parameters under which we localize the invariant domain with unbounded dynamics; this domain is defined with help of bounds for values of the Hamiltonian level surface parameter. We describe one group of conditions when our system possesses two periodic orbits found explicitly. In some of rest cases we get localization bounds for compact invariant sets. - Highlights: • Equations for periodic orbits are got for many level sets. • Domains with unbounded dynamics are localized. • Localizations for compact invariant sets are obtained.

  1. Degassing dynamics of basaltic lava lake at a top-ranking volatile emitter: Ambrym volcano, Vanuatu arc

    Science.gov (United States)

    Allard, Patrick; Burton, Mike; Sawyer, Georgina; Bani, Philipson

    2016-08-01

    Persistent lava lakes are rare on Earth and provide volcanologists with a remarkable opportunity to directly investigate magma dynamics and degassing at the open air. Ambrym volcano, in Vanuatu, is one of the very few basaltic arc volcanoes displaying such an activity and voluminous gas emission, but whose study has long remained hampered by challenging accessibility. Here we report the first high temporal resolution (every 5 s) measurements of vigorous lava lake degassing inside its 300 m deep Benbow crater using OP-FTIR spectroscopy. Our results reveal a highly dynamic degassing pattern involving (i) recurrent (100-200 s) short-period oscillations of the volcanic gas composition and temperature, correlating with pulsated gas emission and sourced in the upper part of the lava lake, (ii) a continuous long period (∼8 min) modulation probably due to the influx of fresh magma at the bottom of the lake, and (iii) discrete CO2 spike events occurring in coincidence with the sequential bursting of meter-sized bubbles, which indicates the separate ascent of large gas bubbles or slugs in a feeder conduit with estimated diameter of 6 ± 1 m. This complex degassing pattern, measured with unprecedented detail and involving both coupled and decoupled magma-gas ascent over short time scales, markedly differs from that of quieter lava lakes at Erebus and Kilauea. It can be accounted for by a modest size of Benbow lava lake and its very high basalt supply rate (∼20 m3 s-1), favouring its rapid overturn and renewal. We verify a typical basaltic arc signature for Ambrym volcanic gas and, based on contemporaneous SO2 flux measurements, we evaluate huge emission rates of 160 Gg d-1 of H2O, ∼10 Gg d-1 of CO2 and ∼8 Gg d-1 of total acid gas (SO2, HCl and HF) during medium activity of the volcano in 2008. Such rates make Ambrym one of the three most powerful volcanic gas emitters at global scale, whose atmospheric impact at local and regional scale may be considerable.

  2. Children's Gender Identity Development: The Dynamic Negotiation Process between Conformity and Authenticity

    Science.gov (United States)

    Brinkman, Britney G; Rabenstein, Kelly L.; Rosén, Lee A.; Zimmerman, Toni S.

    2014-01-01

    In the current study, 45 girls and 41 boys participated in focus groups following a program designed to teach them about social justice. The children articulated the discrepancy between their own gender identity and gender role stereotypes and discussed potential problems with conforming to gender role expectations as well as consequences of…

  3. From flexibility to function: Molecular dynamics simulations of conformational changes in chaperones and photoreceptors

    NARCIS (Netherlands)

    Singhal, K.

    2016-01-01

    Proteins are uniquely-shaped macromolecules that function as biological machines, and regulate a living cell’s behavior. Crucial to protein function is the folding of the polypeptide chain into a unique well-defined three-dimensional conformation. In complex cell environments, the spontaneous unassi

  4. Children's Gender Identity Development: The Dynamic Negotiation Process between Conformity and Authenticity

    Science.gov (United States)

    Brinkman, Britney G; Rabenstein, Kelly L.; Rosén, Lee A.; Zimmerman, Toni S.

    2014-01-01

    In the current study, 45 girls and 41 boys participated in focus groups following a program designed to teach them about social justice. The children articulated the discrepancy between their own gender identity and gender role stereotypes and discussed potential problems with conforming to gender role expectations as well as consequences of…

  5. Children's Gender Identity Development: The Dynamic Negotiation Process between Conformity and Authenticity

    Science.gov (United States)

    Brinkman, Britney G; Rabenstein, Kelly L.; Rosén, Lee A.; Zimmerman, Toni S.

    2014-01-01

    In the current study, 45 girls and 41 boys participated in focus groups following a program designed to teach them about social justice. The children articulated the discrepancy between their own gender identity and gender role stereotypes and discussed potential problems with conforming to gender role expectations as well as consequences of…

  6. Dynamic energy landscapes of riboswitches help interpret conformational rearrangements and function.

    Directory of Open Access Journals (Sweden)

    Giulio Quarta

    Full Text Available Riboswitches are RNAs that modulate gene expression by ligand-induced conformational changes. However, the way in which sequence dictates alternative folding pathways of gene regulation remains unclear. In this study, we compute energy landscapes, which describe the accessible secondary structures for a range of sequence lengths, to analyze the transcriptional process as a given sequence elongates to full length. In line with experimental evidence, we find that most riboswitch landscapes can be characterized by three broad classes as a function of sequence length in terms of the distribution and barrier type of the conformational clusters: low-barrier landscape with an ensemble of different conformations in equilibrium before encountering a substrate; barrier-free landscape in which a direct, dominant "downhill" pathway to the minimum free energy structure is apparent; and a barrier-dominated landscape with two isolated conformational states, each associated with a different biological function. Sharing concepts with the "new view" of protein folding energy landscapes, we term the three sequence ranges above as the sensing, downhill folding, and functional windows, respectively. We find that these energy landscape patterns are conserved in various riboswitch classes, though the order of the windows may vary. In fact, the order of the three windows suggests either kinetic or thermodynamic control of ligand binding. These findings help understand riboswitch structure/function relationships and open new avenues to riboswitch design.

  7. Dynamical approach to conformal gravity and the bosonic string effective action

    Energy Technology Data Exchange (ETDEWEB)

    Barbero, F.; Julve, J.; Tiemblo, A.; Tresguerres, R.

    1988-09-01

    We show that a theory invariant under the full local conformal group in a coset realization contains naturally the massless degrees of freedom of the closed bosonic string. This effective theory is alternative to the bosonic part of supergravity N = 1 as given by Manton and Chapline.

  8. Maintaining Arc Consistency in Non-Binary Dynamic CSPs using Simple Tabular Reduction

    DEFF Research Database (Denmark)

    Queva, Matthieu Stéphane Benoit; Probst, Christian W.; Ricci, Laurent

    2010-01-01

    Constraint Satisfaction Problems (CSPs) are well known models used in Artificial Intelligence. In order to represent real world systems, CSPs have been extended to Dynamic CSPs (DCSPs), which support adding and removing constraints at runtime. Some approaches to the NP-complete problem of solving...

  9. Single-strand conformation polymorphism (SSCP) of oligodeoxyribonucleotides: an insight into solution structural dynamics of DNAs provided by gel electrophoresis and molecular dynamics simulations.

    Science.gov (United States)

    Biyani, Manish; Nishigaki, Koichi

    2005-10-01

    Studies on the solution structure dynamics of RNA/DNA are becoming crucially important. The phenomena of SSCP (single-strand conformation polymorphism), small RNA dynamics in a cell, and others can be related to the conformational changes of single-stranded (ss) RNAs/DNAs in solution. However, little is known about those dynamics. Only the intra-structural transition of ssDNAs in solution has been reported based on Watson-Crick (W-C) base-pairing. Here, we found a general feature of the SSCP phenomenon by studying the simpler molecules of ss-oligodeoxyribonucleotides. A single base substitution or a positional exchange of nucleotide in a highly homologous series of ss-dodecanucleotides led to a change in the mobility-in-gel. This was unexpected, since most of these nucleotides [such as d(A(11)G) or d(A(11)C)] have no possibility of forming W-C base-pairing. MD (molecular dynamics) experiments revealed differences in shape and size between the dynamic structures of these molecules which could affect their mobility-in-gel. In addition, a high correlation was observed between the electrophoretic mobility and the size-related parameters such as end-to-end distance obtained from MD simulations. Because the simulation was considerably shorter (nanosecond) than the experimental time-scale (second), the result must be considered conservatively; but it is nevertheless encouraging for utilizing MD simulation for structural analysis of oligonucleotides.

  10. Post-transcriptional modifications modulate conformational dynamics in human U2-U6 snRNA complex.

    Science.gov (United States)

    Karunatilaka, Krishanthi S; Rueda, David

    2014-01-01

    The spliceosome catalyzes precursor-mRNA splicing in all eukaryotes. It consists of over 100 proteins and five small nuclear RNAs (snRNAs), including U2 and U6 snRNAs, which are essential for catalysis. Human and yeast snRNAs share structural similarities despite the fact that human snRNAs contain numerous post-transcriptional modifications. Although functions for these modifications have been proposed, their exact roles are still not well understood. To help elucidate these roles in pre-mRNA splicing, we have used single-molecule fluorescence to characterize the effect of several post-transcriptional modifications in U2 snRNA on the conformation and dynamics of the U2-U6 complex in vitro. Consistent with yeast, the human U2-U6 complex reveals the presence of a magnesium-dependent dynamic equilibrium among three conformations. Interestingly, our data show that modifications in human U2 stem I modulate the dynamic equilibrium of the U2-U6 complex by stabilizing the four-helix structure. However, the small magnitude of this effect suggests that post-transcriptional modifications in human snRNAs may have a primary role in the mediation of specific RNA-protein interactions in vivo.

  11. Post-transcriptional modifications modulate conformational dynamics in human U2–U6 snRNA complex

    Science.gov (United States)

    Karunatilaka, Krishanthi S.; Rueda, David

    2014-01-01

    The spliceosome catalyzes precursor-mRNA splicing in all eukaryotes. It consists of over 100 proteins and five small nuclear RNAs (snRNAs), including U2 and U6 snRNAs, which are essential for catalysis. Human and yeast snRNAs share structural similarities despite the fact that human snRNAs contain numerous post-transcriptional modifications. Although functions for these modifications have been proposed, their exact roles are still not well understood. To help elucidate these roles in pre-mRNA splicing, we have used single-molecule fluorescence to characterize the effect of several post-transcriptional modifications in U2 snRNA on the conformation and dynamics of the U2–U6 complex in vitro. Consistent with yeast, the human U2–U6 complex reveals the presence of a magnesium-dependent dynamic equilibrium among three conformations. Interestingly, our data show that modifications in human U2 stem I modulate the dynamic equilibrium of the U2–U6 complex by stabilizing the four-helix structure. However, the small magnitude of this effect suggests that post-transcriptional modifications in human snRNAs may have a primary role in the mediation of specific RNA–protein interactions in vivo. PMID:24243115

  12. Dosimetric Comparison of Volumetric Modulated Arc Therapy, Static Field Intensity Modulated Radiation Therapy, and 3D Conformal Planning for the Treatment of a Right-Sided Reconstructed Chest Wall and Regional Nodal Case

    Directory of Open Access Journals (Sweden)

    Vishruta A. Dumane

    2014-01-01

    Full Text Available We compared 3D conformal planning, static field intensity modulated radiation therapy (IMRT, and volumetric modulated arc therapy (VMAT to investigate the suitable treatment plan and delivery method for a right-sided reconstructed chest wall and nodal case. The dose prescribed for the reconstructed chest wall and regional nodes was 50.4 Gy. Plans were compared for target coverage and doses of the lungs, heart, contralateral breast, and healthy tissue. All plans achieved acceptable coverage of the target and IMNs. The best right lung sparing achieved with 3D was a V20 Gy of 31.09%. Compared to it, VMAT reduced the same by 10.85% and improved the CI and HI over 3D by 18.75% and 2%, respectively. The ipsilateral lung V5 Gy to V20 Gy decreased with VMAT over IMRT by as high as 17.1%. The contralateral lung V5 Gy was also lowered with VMAT compared to IMRT by 16.22%. The MU and treatment beams were lowered with VMAT over IMRT by 30% and 10, respectively, decreasing the treatment time by >50%. VMAT was the treatment plan and delivery method of choice for this case due to a combination of improved lung sparing and reduced treatment time without compromising target coverage.

  13. Conformations of Carnosine in Aqueous Solutions by All-Atom Molecular Dynamics Simulations and 2D-NOSEY Spectrum

    Institute of Scientific and Technical Information of China (English)

    Rong Zhang; Dan Wang; Wen-juan Wu

    2013-01-01

    All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution.Intramolecular distances,root-mean-square deviation,radius of gyration,and solvent-accessible surface are used to characterize the properties of the carnosine.Carnosine can shift between extended and folded states,but exists mostly in extended state in water.Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance (NMR) experiment.The NMR experimental results are consistent with the molecular dynamics simulations.

  14. Cathodic arcs

    Energy Technology Data Exchange (ETDEWEB)

    Anders, Andre

    2003-10-29

    Cathodic arc plasma deposition has become the technology of choice for hard, wear and corrosion resistant coatings for a variety of applications. The history, basic physics of cathodic arc operation, the infamous macroparticle problem and common filter solutions, and emerging high-tech applications are briefly reviewed. Cathodic arc plasmas standout due to their high degree of ionization, with important consequences for film nucleation, growth, and efficient utilization of substrate bias. Industrial processes often use cathodic arc plasma in reactive mode. In contrast, the science of arcs has focused on the case of vacuum arcs. Future research directions include closing the knowledge gap for reactive mode, large area coating, linear sources and filters, metal plasma immersion process, with application in high-tech and biomedical fields.

  15. Acyclic forms of aldohexoses and ketohexoses in aqueous and DMSO solutions: conformational features studied using molecular dynamics simulations.

    Science.gov (United States)

    Plazinski, Wojciech; Plazinska, Anita; Drach, Mateusz

    2016-04-14

    The molecular properties of aldohexoses and ketohexoses are usually studied in the context of their cyclic, furanose or pyranose structures which is due to the abundance of related tautomeric forms in aqueous solution. We studied the conformational features of a complete series of D-aldohexoses (D-allose, D-altrose, D-glucose, D-mannose, D-gulose, d-idose, D-galactose and D-talose) and D-ketohexoses (D-psicose, D-fructose, D-sorbose and D-tagatose) as well as of L-psicose by using microsecond-timescale molecular dynamics in explicit water and DMSO with the use of enhanced sampling methods. In each of the studied cases the preferred conformation corresponded to an extended chain structure; the less populated conformers included the quasi-cyclic structures, close to furanose rings and common for both aldo- and ketohexoses. The orientational preferences of the aldehyde or ketone groups are correlated with the relative populations of anomers characteristic of cyclic aldo- and ketohexoses, respectively, thus indicating that basic features of anomeric equilibria are preserved even if hexose molecules are not in their cyclic forms. No analogous relationship is observed in the case of other structural characteristics, such as the preferences of acyclic molecules to form either the furanose-or pyranose-like structures or maintaining the chair-like geometry of pseudo-pyranose rings.

  16. Conformational change upon ligand binding and dynamics of the PDZ domain from leukemia-associated Rho guanine nucleotide exchange factor.

    Science.gov (United States)

    Liu, Jiangxin; Zhang, Jiahai; Yang, Yinshan; Huang, Hongda; Shen, Weiqun; Hu, Qi; Wang, Xingsheng; Wu, Jihui; Shi, Yunyu

    2008-06-01

    Leukemia-associated Rho guanine nucleotide exchange factor (LARG) is a RhoA-specific guanine nucleotide exchange factor (GEF) that can activate RhoA. The PDZ (PSD-95/Disc-large/ZO-1 homology) domain of LARG interacts with membrane receptors, which can relay extracellular signals to RhoA signal transduction pathways. Until now there is no structural and dynamic information about these interactions. Here we report the NMR structures of the LARG PDZ in the apo form and in complex with the plexin-B1 C-terminal octapeptide. Unobservable resonances of the residues in betaB/betaC and betaE/alphaB loops in apo state were observed in the complex state. A distinct region of the binding groove in the LARG PDZ was found to undergo conformational change compared with other PDZs. Analysis of the (15)N relaxation data using reduced spectral density mapping shows that the apo LARG PDZ (especially its ligand-binding groove) is flexible and exhibits internal motions on both picosecond to nanosecond and microsecond to millisecond timescales. Mutagenesis and thermodynamic studies indicate that the conformation of the betaB/betaC and betaE/alphaB loops affects the PDZ-peptide interaction. It is suggested that the conformational flexibility could facilitate the change of structures upon ligand binding.

  17. Cathodic arcs

    OpenAIRE

    Anders, Andre

    2003-01-01

    Cathodic arc plasma deposition has become the technology of choice for hard, wear and corrosion resistant coatings for a variety of applications. The history, basic physics of cathodic arc operation, the infamous macroparticle problem and common filter solutions, and emerging high-tech applications are briefly reviewed. Cathodic arc plasmas stand out due to their high degree of ionization, with important consequences for film nucleation, growth, and efficient utilization of substrate bia...

  18. The broadband microwave spectra of the monoterpenoids thymol and carvacrol: Conformational landscape and internal dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, D.; Shubert, V. A. [Max Planck Institute for the Structure and Dynamics of Matter, Hamburg (Germany); The Center for Free-Electron Laser Science, Hamburg (Germany); Giuliano, B. M. [Center for Astrobiology, INTA-CSIC, Torrejón de Ardoz, Madrid (Spain); Schnell, M., E-mail: melanie.schnell@mpsd.mpg.de [Max Planck Institute for the Structure and Dynamics of Matter, Hamburg (Germany); The Center for Free-Electron Laser Science, Hamburg (Germany); The Hamburg Centre for Ultrafast Imaging, Universität Hamburg, Hamburg (Germany)

    2014-07-21

    The rotational spectra of the monoterpenoids thymol and carvacrol are reported in the frequency range 2–8.5 GHz, obtained with broadband Fourier-transform microwave spectroscopy. For carvacrol four different conformations were identified in the cold conditions of the molecular jet, whereas only three conformations were observed for thymol. The rotational constants and other molecular parameters are reported and compared with quantum chemical calculations. For both molecules, line splittings due to methyl group internal rotation were observed and the resulting barrier heights could be determined. The experimental barrier heights, 4.0863(25) kJ/mol for trans-carvacrol-A, 4.4024(16) kJ/mol for trans-carvacrol-B, and 0.3699(11) kJ/mol for trans-thymol-A, are compared with similar molecules.

  19. Long-Range Conformational Response of a PDZ Domain to Ligand Binding and Release: A Molecular Dynamics Study.

    Science.gov (United States)

    Lu, Cheng; Knecht, Volker; Stock, Gerhard

    2016-02-09

    The binding of a ligand to a protein may induce long-range structural or dynamical changes in the biomacromolecule even at sites physically well separated from the binding pocket. A system for which such behavior has been widely discussed is the PDZ2 domain of human tyrosine phosphatase 1E. Here, we present results from equilibrium trajectories of the PDZ2 domain in the free and ligand-bound state, as well as nonequilibrium simulations of the relaxation of PDZ2 after removal of its peptide ligand. The study reveals changes in inter-residue contacts, backbone dihedral angles, and C(α) positions upon ligand release. Our findings show a long-range conformational response of the PDZ2 domain to ligand release in the form of a collective shift of the secondary structure elements α2, β2, β3, α1-β4, and the C terminal loop relative to the rest of the protein away from the N-terminus, and a shift of the loops β2-β3 and β1-β2 in the opposite direction. The shifts lead to conformational changes in the backbone, especially in the β2-β3 loop but also in the β5-α2 and the α2-β6 loop, and are accompanied by changes of inter-residue contacts mainly within the β2-β3 loop as well as between the α2 helix and other segments. The residues showing substantial changes of inter-residue contacts, backbone conformations, or C(α) positions are considered "key residues" for the long-range conformational response of PDZ2. By comparing these residues with various sets of residues highlighted by previous studies of PDZ2, we investigate the statistical correlation of the various approaches. Interestingly, we find a considerable correlation of our findings with several works considering structural changes but no significant correlations with approaches considering energy flow or networks based on inter-residue energies.

  20. Effect of hydrophobic groups on the adsorption conformation of modified polycarboxylate superplasticizer investigated by molecular dynamics simulation

    Science.gov (United States)

    Zhao, Hongxia; Wang, Yanwei; Yang, Yong; Shu, Xin; Yan, Han; Ran, Qianping

    2017-06-01

    All-atom molecular dynamics (MD) simulations were used to study the adsorption conformations of hydrophobically-modified comb-shaped polycarboxylate ether-based (PCE) superplasticizer molecules on a model surface of dicalcium silicate (C2S) in vacuum and in an explicit solution, respectively. Three different hydrophobic modifying groups, namely, the ethyl group, the n-butyl group and the phenyl group, decorated to the backbone, were examined. Comparing the hydrophobically-modified PCEs to the unmodified one, differences were found in the binding energy, the adsorption conformation and the water density at the interface. The interaction between PCE molecules and C2S was weakened in a solution with explicit solvents than that obtained from vacuum-based simulations. The presence of hydrophobic groups lowered the polymer-surface binding energy, decreased the radius of gyration (Rg) of the adsorbed polymer, increased the peak position in the heavy-atom density profiles in the direction perpendicular to the surface, and also caused the adsorbed conformations to be more globular in shape. The parallel and perpendicular components (relative to the surface plane) of the geometric sizes of the adsorbed polymers were calculated, and the results showed that the presence of hydrophobically modifying groups decreased the in-plane radius while increased the adsorption layer thickness compared to the unmodified control. The presence of PCEs perturbed the dense water layer above the C2S surface and lowered the water density. Perturbations to the interfacial water density were found to correlate nicely with the adsorbed conformations of PCEs.

  1. The dynamics of back-arc extension: an experimental approach to the opening of the Tyrrhenian Sea

    Science.gov (United States)

    Faccenna, Claudio; Davy, Philippe; Brun, Jean-Pierre; Funiciello, Renato; Giardini, Domenico; Mattei, Massimo; Nalpas, Thierry

    1996-09-01

    The E-W-opening Tyrrhenian Sea developed after the Cretaceous-Palaeogene Alpine collision, nearly perpendicular to the motion of the African plate, as a back-arc of the Adria-Ionian westward subduction. Three driving mechanisms have been proposed to explain the dynamic evolution of the Tyrrhenian-Apennine system: (1) the northward indentation of the African plate; (2) the retreating subduction of the Adria-Ionian lithosphere; and (3) the gravitational collapse of the Alpine post-collisional wedge. In order to define the relative contribution of each of these mechanisms in the Neogene dynamic of the Tyrrhenian-Apennine system, we performed 3-D laboratory experiments, in which we simulated a retreating subduction process in a compressional regime oriented perpendicularly to the direction of subduction; in this framework we also tested the influence of the gravitational collapse of the overriding plate. Experiments were constructed using dry sand and silicone putties to simulate brittle upper crust and ductile lower crust/upper mantle, respectively; these layers floated on a high-density, low-viscosity glucose syrup which simulated the asthenosphere. The main conclusion of our experiments is that large-scale continental extension, similar to that observed in the Tyrrhenian area, could be reproduced perpendicular to the shortening direction induced by the indentation of the African plate; in this framework, extensional processes are indeed possible if the trench retreat velocity is higher than the rate of shortening induced by the advancing African plate. Our experimental results indicate that this high trench retreat velocity could be explained by the coexistence of the gravitational collapse of the post-Alpine wedge with a slab-pull process, linked to the retreating subduction of the Adria-Ionian plate. While the first mechanism is predominant in the Northern Tyrrhenian area, the second one seems to be important in the latest stage of extension and oceanic accretion

  2. The Tachakoucht-Iriri-Tourtit arc complex (Moroccan Anti-Atlas): Neoproterozoic records of polyphased subduction-accretion dynamics during the Pan-African orogeny

    Science.gov (United States)

    Triantafyllou, Antoine; Berger, Julien; Baele, Jean-Marc; Diot, Hervé; Ennih, Nasser; Plissart, Gaëlle; Monnier, Christophe; Watlet, Arnaud; Bruguier, Olivier; Spagna, Paul; Vandycke, Sara

    2016-05-01

    -Atlas belt and that they were separated by an early accretion of the intra-oceanic arc system (IOAS) onto the West African craton passive margin. Our interpretations also validate thermo-mechanical models predicting an intense perturbation of subduction dynamics during arc-continent collision (i.e. composite subductions, polarity reversal) which can expand the production of typical hydrous arc magma and induces a late magmatic phase after partial or total accretion of the IOAS.

  3. Molecular dynamics simulation of phosphorylation-induced conformational transitions in the mycobacterium tuberculosis response regulator PrrA

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Guo [Los Alamos National Laboratory; Mcmahon, Benjamin H [Los Alamos National Laboratory; Tung, Chang - Shung [Los Alamos National Laboratory

    2008-01-01

    Phosphorylation-activated modulation of response regulators (RR) is predominantly used by bacteria as a strategy in regulating their two-component signaling (TCS) systems, the underlying molecular mechanisms are however far from fully understood. In this work we have conducted a molecular dynamics (MD) simulation of the phosphorylation-induced conformational transitions of RRs with the Mycobacterium Tuberculosis PrrA as a particular example. Starting from the full-length inactive structure of PrrA we introduced a local disturbance by phosphorylating the conserved aspartic acid residue, Asp-58, in the regulatory domain. A Go-model-type algorithm packaged with AMBER force fields was then applied to simulate the dynamics upon phosphorylation. The MD simulation shows that the phosphorylation of Asp-58 facilitates PrrA, whose inactive state has a compact conformation with a closed interdomain interface, to open up with its interdomain separation being increased by an average of about 1.5 {angstrom} for a simulation of 20 ns. The trans-activation loop, which is completely buried within the interdomain interface in the inactive PrrA, is found to become more exposed with the phosphorylated structure as well. These results provide more structural details of how the phosphorylation of a local aspartate activates PrrA to undergo a global conformational rearrangement toward its extended active state. This work also indicates that MD simulations can serve as a fast tool to unravel the regulation mechanisms of all RRs, which is especially valuable when the structures of full-length active RRs are currently unavailable.

  4. Kinetic adsorption profile and conformation evolution at the DNA-gold nanoparticle interface probed by dynamic light scattering.

    Science.gov (United States)

    Wang, Wenjie; Ding, XiaoFan; He, Miao; Wang, Jing; Lou, Xinhui

    2014-10-21

    The kinetic adsorption profile at the DNA-gold nanoparticle (AuNP) interface is probed by following the binding and organization of thiolated linear DNA and aptamers of varying chain lengths (15, 30, 44, and 51 mer) to the surface of AuNPs (13.0 ± 1.0 nm diameter). A systematic investigation utilizing dynamic light scattering has been performed to directly measure the changes in particle size during the course of a typical aging-salting thiolated DNA/AuNP preparation procedure. We discuss the effect of DNA chain length, composition, salt concentration, and secondary structure on the kinetics and conformation at the DNA-AuNP interface. The adsorption kinetics are chain-length dependent, composition independent, and not diffusion rate limited for the conditions we report here. The kinetic data support a mechanism of stepwise adsorption of thiols to the surface of AuNPs and reorganization of the thiols at the interface. Very interestingly, the kinetic increases of the particle sizes are modeled accurately by the pseudo-second-order rate model, suggesting that DNA could possess the statistically well-defined conformational evolution. Together with other experimental evidence, we propose a dynamic inner-layer and outer-tail (DILOT) model to describe the evolution of the DNA conformation after the initial adsorption of a single oligonucleotide layer. According to this model, the length of the tails that extend from the surface of AuNPs, capable for hybridization or molecular recognition, can be conveniently calculated. Considering the wide applications of DNA/AuNPs, the results should have important implications in sensing and DNA-directed nanoparticle assembly.

  5. Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1.

    Science.gov (United States)

    Desjardins, Geneviève; Okon, Mark; Graves, Barbara J; McIntosh, Lawrence P

    2016-07-26

    The affinity of the Ets-1 transcription factor for DNA is autoinhibited by an intrinsically disordered serine-rich region (SRR) and a helical inhibitory module (IM) appended to its winged helix-turn-helix ETS domain. Using NMR spectroscopy, we investigated how Ets-1 recognizes specific versus nonspecific DNA, with a focus on the roles of protein dynamics and autoinhibition in these processes. Upon binding either DNA, the two marginally stable N-terminal helices of the IM predominantly unfold, but still sample partially ordered conformations. Also, on the basis of amide chemical shift perturbation mapping, Ets-1 associates with both specific and nonspecific DNA through the same canonical ETS domain interface. These interactions are structurally independent of the SRR, and thus autoinhibition does not impart DNA-binding specificity. However, relative to the pronounced NMR spectroscopic changes in Ets-1 resulting from specific DNA binding, the spectra of the nonspecific DNA complexes showed conformational exchange broadening and lacked several diagnostic amide and indole signals attributable to hydrogen bonding interactions seen in reported X-ray crystallographic structures of this transcription factor with its cognate DNA sequences. Such differences are highlighted by the chemical shift and relaxation properties of several interfacial lysine and arginine side chains. Collectively, these data support a general model in which Ets-1 interacts with nonspecific DNA via dynamic electrostatic interactions, whereas hydrogen bonding drives the formation of well-ordered complexes with specific DNA.

  6. Effect of graphene oxide on the conformational transitions of amyloid beta peptide: A molecular dynamics simulation study.

    Science.gov (United States)

    Baweja, Lokesh; Balamurugan, Kanagasabai; Subramanian, Venkatesan; Dhawan, Alok

    2015-09-01

    The interactions between nanomaterials (NMs) and amyloid proteins are central to the nanotechnology-based diagnostics and therapy in neurodegenerative disorders such as Alzheimer's and Parkinson's. Graphene oxide (GO) and its derivatives have shown to modulate the aggregation pattern of disease causing amyloid beta (Aβ) peptide. However, the mechanism is still not well understood. Using molecular dynamics simulations, the effect of graphene oxide (GO) and reduced graphene oxide (rGO) having carbon:oxygen ratio of 4:1 and 10:1, respectively, on the conformational transitions (alpha-helix to beta-sheet) and the dynamics of the peptide was investigated. GO and rGO decreased the beta-strand propensity of amino acid residues in Aβ. The peptide displayed different modes of adsorption on GO and rGO. The adsorption on GO was dominated by electrostatic interactions, whereas on rGO, both van der Waals and electrostatic interactions contributed in the adsorption of the peptide. Our study revealed that the slight increase in the hydrophobic patches on rGO made it more effective inhibitor of conformational transitions in the peptide. Alpha helix-beta sheet transition in Aβ peptide could be one of the plausible mechanism by which graphene oxide may inhibit amyloid fibrillation.

  7. Molecular Dynamics Simulation on the Conformational Transition of the Mad2 Protein from the Open to the Closed State

    Directory of Open Access Journals (Sweden)

    Chaoqun Li

    2014-03-01

    Full Text Available The Mad2 protein, with two distinct conformations of open- and closed-states, is a key player in the spindle checkpoint. The closed Mad2 state is more active than the open one. We carried out conventional and targeted molecular dynamics simulations for the two stable Mad2 states and their conformational transition to address the dynamical transition mechanism from the open to the closed state. The intermediate structure in the transition process shows exposure of the β6 strand and an increase of space around the binding sites of β6 strand due to the unfolding of the β7/8 sheet and movement of the β6/4/5 sheet close to the αC helix. Therefore, Mad2 binding to the Cdc20 protein in the spindle checkpoint is made possible. The interconversion between these two states might facilitate the functional activity of the Mad2 protein. Motion correlation analysis revealed the allosteric network between the β1 strand and β7/8 sheet via communication of the β5-αC loop and the β6/4/5 sheet in this transition process.

  8. Molecular Dynamics Simulation of Tau Peptides for the Investigation of Conformational Changes Induced by Specific Phosphorylation Patterns.

    Science.gov (United States)

    Gandhi, Neha S; Kukic, Predrag; Lippens, Guy; Mancera, Ricardo L

    2017-01-01

    The Tau protein plays an important role due to its biomolecular interactions in neurodegenerative diseases. The lack of stable structure and various posttranslational modifications such as phosphorylation at various sites in the Tau protein pose a challenge for many experimental methods that are traditionally used to study protein folding and aggregation. Atomistic molecular dynamics (MD) simulations can help around deciphering relationship between phosphorylation and various intermediate and stable conformations of the Tau protein which occur on longer timescales. This chapter outlines protocols for the preparation, execution, and analysis of all-atom MD simulations of a 21-amino acid-long phosphorylated Tau peptide with the aim of generating biologically relevant structural and dynamic information. The simulations are done in explicit solvent and starting from nearly extended configurations of the peptide. The scaled MD method implemented in AMBER14 was chosen to achieve enhanced conformational sampling in addition to a conventional MD approach, thereby allowing the characterization of folding for such an intrinsically disordered peptide at 293 K. Emphasis is placed on the analysis of the simulation trajectories to establish correlations with NMR data (i.e., chemical shifts and NOEs). Finally, in-depth discussions are provided for commonly encountered problems.

  9. Conformational Dynamics and Binding Free Energies of Inhibitors of BACE-1: From the Perspective of Protonation Equilibria.

    Directory of Open Access Journals (Sweden)

    M Olivia Kim

    2015-10-01

    Full Text Available BACE-1 is the β-secretase responsible for the initial amyloidogenesis in Alzheimer's disease, catalyzing hydrolytic cleavage of substrate in a pH-sensitive manner. The catalytic mechanism of BACE-1 requires water-mediated proton transfer from aspartyl dyad to the substrate, as well as structural flexibility in the flap region. Thus, the coupling of protonation and conformational equilibria is essential to a full in silico characterization of BACE-1. In this work, we perform constant pH replica exchange molecular dynamics simulations on both apo BACE-1 and five BACE-1-inhibitor complexes to examine the effect of pH on dynamics and inhibitor binding properties of BACE-1. In our simulations, we find that solution pH controls the conformational flexibility of apo BACE-1, whereas bound inhibitors largely limit the motions of the holo enzyme at all levels of pH. The microscopic pKa values of titratable residues in BACE-1 including its aspartyl dyad are computed and compared between apo and inhibitor-bound states. Changes in protonation between the apo and holo forms suggest a thermodynamic linkage between binding of inhibitors and protons localized at the dyad. Utilizing our recently developed computational protocol applying the binding polynomial formalism to the constant pH molecular dynamics (CpHMD framework, we are able to obtain the pH-dependent binding free energy profiles for various BACE-1-inhibitor complexes. Our results highlight the importance of correctly addressing the binding-induced protonation changes in protein-ligand systems where binding accompanies a net proton transfer. This work comprises the first application of our CpHMD-based free energy computational method to protein-ligand complexes and illustrates the value of CpHMD as an all-purpose tool for obtaining pH-dependent dynamics and binding free energies of biological systems.

  10. On the Chern-Gauss-Bonnet Theorem and Conformally Twisted Spectral Triples for C-Dynamical Systems

    DEFF Research Database (Denmark)

    Fathizadeh, Farzad; Gabriel, Olivier

    2016-01-01

    subalgebra A ⊂ A as noncommutative dif ferential forms on the dynamical system. We conformally perturb the standard metric, which is associated with the unique G-invariant state on A, by means of a Weyl conformal factor given by a positive invertible element of the algebra, and consider the Hermitian......The analog of the Chern–Gauss–Bonnet theorem is studied for a C ∗ -dynamical system consisting of a C ∗ -algebra A equipped with an ergodic action of a compact Lie group G. The structure of the Lie algebra g of G is used to interpret the Chevalley–Eilenberg complex with coef ficients in the smooth...... construction of a spectral triple on A and a twisted spectral triple on its opposite algebra. The conformal invariance of the Euler characteristic is interpreted as an indication of the Chern–Gauss–Bonnet theorem in this setting. The spectral triples encoding the conformally perturbed metrics are shown...

  11. Dynamic Conformational Change Regulates the Protein-DNA Recognition: An Investigation on Binding of a Y-Family Polymerase to Its Target DNA

    Science.gov (United States)

    Chu, Xiakun; Liu, Fei; Maxwell, Brian A.; Wang, Yong; Suo, Zucai; Wang, Haijun; Han, Wei; Wang, Jin

    2014-01-01

    Protein-DNA recognition is a central biological process that governs the life of cells. A protein will often undergo a conformational transition to form the functional complex with its target DNA. The protein conformational dynamics are expected to contribute to the stability and specificity of DNA recognition and therefore may control the functional activity of the protein-DNA complex. Understanding how the conformational dynamics influences the protein-DNA recognition is still challenging. Here, we developed a two-basin structure-based model to explore functional dynamics in Sulfolobus solfataricus DNA Y-family polymerase IV (DPO4) during its binding to DNA. With explicit consideration of non-specific and specific interactions between DPO4 and DNA, we found that DPO4-DNA recognition is comprised of first 3D diffusion, then a short-range adjustment sliding on DNA and finally specific binding. Interestingly, we found that DPO4 is under a conformational equilibrium between multiple states during the binding process and the distributions of the conformations vary at different binding stages. By modulating the strength of the electrostatic interactions, the flexibility of the linker, and the conformational dynamics in DPO4, we drew a clear picture on how DPO4 dynamically regulates the DNA recognition. We argue that the unique features of flexibility and conformational dynamics in DPO4-DNA recognition have direct implications for low-fidelity translesion DNA synthesis, most of which is found to be accomplished by the Y-family DNA polymerases. Our results help complete the description of the DNA synthesis process for the Y-family polymerases. Furthermore, the methods developed here can be widely applied for future investigations on how various proteins recognize and bind specific DNA substrates. PMID:25188490

  12. Conformational selection and functional dynamics of calmodulin: a (19)F nuclear magnetic resonance study.

    Science.gov (United States)

    Hoang, Joshua; Prosser, R Scott

    2014-09-16

    Calcium-bound calmodulin (CaM-4Ca(2+)) is innately promiscuous with regard to its protein interaction network within the cell. A key facet of the interaction process involves conformational selection. In the absence of a binding peptide, CaM-4Ca(2+) adopts an equilibrium between a native state (N) and a weakly populated near-native peptide-bound-like state (I), whose lifetime is on the order of 1.5 ms at 37 °C, based on (19)F nuclear magnetic resonance (NMR) Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion measurements. This peptide-bound-like state of CaM-4Ca(2+) is entropically stabilized (ΔS = 280 ± 35 J mol(-1) K(-1)) relative to the native state, water-depleted, and likely parental to specific bound states. Solvent depletion, conformational selection, and flexibility of the peptide-bound-like state may be important in priming the protein for binding. At higher temperatures, the exchange rate, kex, appears to markedly slow, suggesting the onset of misfolded or off-pathway states, which retards interconversion between N and I. (19)F NMR CPMG relaxation dispersion experiments with both CaM-4Ca(2+) and the separate N-terminal and C-terminal domains reveal the cooperative role of the two domains in the binding process and the flexibility of the N-terminal domain in facilitating binding. Thus, when calcium binds, calmodulin establishes its interaction with a multitude of protein binding partners, through a combination of conformational selection to a state that is parental to the peptide-bound state and, finally, induced fit.

  13. Conformational Dynamics of hSGLT1 during Na+/Glucose Cotransport

    DEFF Research Database (Denmark)

    Loo, D. D.; Hirayama, B. A.; Karakossian, M. H.

    2006-01-01

    . voltage (Q-V) and fluorescence vs. voltage ( F-V) relations (for medium and slow components) obeyed Boltzmann relations with similar parameters: z (apparent valence of voltage sensor) 1; and V0.5 (midpoint voltage) between -15 and -40 mV. Sugar induced an inward current (Na+/glucose cotransport......This study examines the conformations of the Na+/glucose cotransporter (SGLT1) during sugar transport using charge and fluorescence measurements on the human SGLT1 mutant G507C expressed in Xenopus oocytes. The mutant exhibited similar steady-state and presteady-state kinetics as wild-type SGLT1...

  14. Structure and conformational dynamics of molecules in the excited electronic states: theory and experiment

    Science.gov (United States)

    Godunov, I. A.; Bataev, V. A.; Maslov, D. V.; Yakovlev, N. N.

    2016-12-01

    The structure of conformational non-rigid molecules in the excited electronic states are investigated by joint theoretical and experimental methods. The theoretical part of work consist of two stages. In first stage the ab initio quantum-chemical calculations are carried out using high level methods. In second stage the vibrational problems of the various dimensions are solved by variational method for vibrations of large amplitude. In experimental part of work the vibronic spectra are investigated: gas-phase absorption and also, fluorescence excitation spectra of jet-cooled molecules. Some examples are considered.

  15. Dynamics of the His79-heme Alkaline Transition of Yeast Iso-1-cytochrome c Probed by Conformationally-gated Electron Transfer with Co(II)bis(terpyridine)†

    Science.gov (United States)

    Cherney, Melisa M.; Junior, Carolyn C.; Bergquist, Bryan B.; Bowler, Bruce E.

    2013-01-01

    Alkaline conformers of cytochrome c may be involved in both its electron transport and apoptotic functions. We use cobalt(II)bis(terpyridine), Co(terpy)22+, as a reagent for conformationally-gated electron transfer (gated ET) experiments to study the alkaline conformational transition of K79H variants of yeast iso-1-cytochrome c expressed in Escherichia coli, WT*K79H, with alanine at position 72, and Saccharomyces cerevisiae, yK79H, with trimethyllysine (Tml) at position 72. Co(terpy)22+ is well-suited to the 100 ms to 1 s time scale of the His79-mediated alkaline conformational transition of these variants. Reduction of the His79-heme alkaline conformer by Co(terpy)22+ occurs primarily by gated ET, which involves conversion to the native state followed by reduction, with a small fraction of the His79- heme alkaline conformer directly reduced by Co(terpy)22+. The gated ET experiments show that the mechanism of formation of the His79-heme alkaline conformer involves only two ionizable groups. In previous work, we showed that the mechanism of the His73-mediated alkaline conformational transition requires three ionizable groups. Thus, the mechanism of heme crevice opening depends upon the position of the ligand mediating the process. The microscopic rate constants provided by gated ET studies show that mutation of Tml72 (yK79H variant) in the heme crevice loop to Ala72 (WT*K79H variant) affects the dynamics of heme crevice opening through a small destabilization of both the native conformer and the transition state relative to the His79-heme alkaline conformer. Previous pH jump data had indicated that the Tml72→Ala mutation primarily stabilized the transition state for the His79-mediated alkaline conformational transition. PMID:23899348

  16. 弧翼飞行器柔性飞行动力学研究%Study on Flexible Flight Dynamics of an Arc-wing Aicrraft

    Institute of Scientific and Technical Information of China (English)

    杜欢; 王正平

    2014-01-01

    以一种弧翼布局飞行器为背景,介绍了飞行器的特性;建立了线性分布式气动力模型,添加到全机的三维有限元柔性模型上,进行飞行动力学的仿真分析。研究了分布式气动力模型对弧翼布局飞行器的柔性飞行动力学特性造成的影响。通过对不同响应情况下的飞行状态的仿真计算与分析,总结出了采用分布式气动力建模的大展弦比弧翼飞行器的柔性飞行动力学的变化规律。%The characteristics of an arc-wing aircraft are introduced .A distributed aerodynamic force mode are established and applied on three-dimensional finite element flexible-body aircraft models for an arc-wing aircraft .Flight dynamics simulation was processed .This paper mainly studied the effect of dis-tributed aerodynamic force model to the flexible flight dynamics of the arc-wing aircraft .Through the sim-ulation and analysis of the different responses under flight conditions ,corresponding rules of the flexible flight dynamics of high-aspect-ratio arc-wing aircraft which used the distributed aerodynamic force mod-els was summarized .

  17. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Directory of Open Access Journals (Sweden)

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  18. SUMO-1 regulates the conformational dynamics of Thymine-DNA Glycosylase regulatory domain and competes with its DNA binding activity

    Directory of Open Access Journals (Sweden)

    Eilebrecht Sebastian

    2011-02-01

    Full Text Available Abstract Background The human thymine-DNA glycosylase (TDG plays a dual role in base excision repair of G:U/T mismatches and in transcription. Regulation of TDG activity by SUMO-1 conjugation was shown to act on both functions. Furthermore, TDG can interact with SUMO-1 in a non-covalent manner. Results Using NMR spectroscopy we have determined distinct conformational changes in TDG upon either covalent sumoylation on lysine 330 or intermolecular SUMO-1 binding through a unique SUMO-binding motif (SBM localized in the C-terminal region of TDG. The non-covalent SUMO-1 binding induces a conformational change of the TDG amino-terminal regulatory domain (RD. Such conformational dynamics do not exist with covalent SUMO-1 attachment and could potentially play a broader role in the regulation of TDG functions for instance during transcription. Both covalent and non-covalent processes activate TDG G:U repair similarly. Surprisingly, despite a dissociation of the SBM/SUMO-1 complex in presence of a DNA substrate, SUMO-1 preserves its ability to stimulate TDG activity indicating that the non-covalent interactions are not directly involved in the regulation of TDG activity. SUMO-1 instead acts, as demonstrated here, indirectly by competing with the regulatory domain of TDG for DNA binding. Conclusions SUMO-1 increases the enzymatic turnover of TDG by overcoming the product-inhibition of TDG on apurinic sites. The mechanism involves a competitive DNA binding activity of SUMO-1 towards the regulatory domain of TDG. This mechanism might be a general feature of SUMO-1 regulation of other DNA-bound factors such as transcription regulatory proteins.

  19. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Directory of Open Access Journals (Sweden)

    Joseph L Baker

    2013-04-01

    Full Text Available Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon

  20. Intramolecular interactions stabilizing compact conformations of the intrinsically disordered kinase-inhibitor domain of Sic1: a molecular dynamics investigation.

    Directory of Open Access Journals (Sweden)

    Matteo eLambrughi

    2012-11-01

    Full Text Available Cyclin-dependent kinase inhibitors (CKIs are key regulatory proteins of the eukaryotic cell cycle, which modulate cyclin-dependent kinase (Cdk activity. CKIs perform their inhibitory effect by the formation of ternary complexes with a target kinase and its cognate cyclin. These regulators generally belong to the class of intrinsically disordered proteins (IDPs, which lack a well-defined and organized three-dimensional structure in their free state, undergoing folding upon binding to specific partners. Unbound IDPs are not merely random-coil structures, but can present intrinsically folded structural units (IFSUs and collapsed conformations. These structural features can be relevant to protein function in vivo.The yeast CKI Sic1 is a 284-amino acid IDP that binds to Cdk1 in complex with the Clb5,6 cyclins, preventing phosphorylation of G1 substrates and, therefore, entrance to the S phase. Sic1 degradation, triggered by multiple phosphorylation events, promotes cell-cycle progression. Previous experimental studies pointed out a propensity of Sic1 and its isolated domains to populate both extended and compact conformations. The present contribution provides models of the compact conformations of the Sic1 kinase-inhibitory domain (KID by all-atom molecular-dynamics simulations in explicit solvent and in the absence of interactors. The results are integrated by spectroscopic and spectrometric data. Helical IFSUs are identified, along with networks of intramolecular interactions. The results identify a group of hub residues and electrostatic interactions which are likely to be involved in the stabilization of globular states.

  1. ON THE APPROXIMATION OF SOLVENT EFFECTS ON THE CONFORMATION AND DYNAMICS OF CYCLOSPORIN A BY STOCHASTIC DYNAMICS SIMULATION TECHNIQUES

    NARCIS (Netherlands)

    Shi Yun-yu, [No Value; Wang Lu, [No Value; Van Gunsteren, W. F.

    1988-01-01

    The molecular simulation technique of stochastic dynamics (SD) is tested by application to the immunosuppressive drug cyclosporin A (CPA). Two stochastic dynamics simulations are performed, one (SDCCl4) with atomic friction coefficients proportional to the viscosity of the nonpolar solvent CCl4, and

  2. Inter-helical conformational preferences of HIV-1 TAR-RNA from maximum occurrence analysis of NMR data and molecular dynamics simulations.

    Science.gov (United States)

    Andrałojć, Witold; Ravera, Enrico; Salmon, Loïc; Parigi, Giacomo; Al-Hashimi, Hashim M; Luchinat, Claudio

    2016-02-17

    Detecting conformational heterogeneity in biological macromolecules is a key for the understanding of their biological function. We here provide a comparison between two independent approaches to assess conformational heterogeneity: molecular dynamics simulations, performed without inclusion of any experimental data, and maximum occurrence (MaxOcc) distribution over the topologically available conformational space. The latter only reflects the extent of the averaging and identifies regions which are most compliant with the experimentally measured NMR Residual Dipolar Couplings (RDCs). The analysis was performed for the HIV-1 TAR RNA, consisting of two helical domains connected by a flexible bulge junction, for which four sets of RDCs were available as well as an 8.2 μs all-atom molecular dynamics simulation. A sample and select approach was previously applied to extract from the molecular dynamics trajectory conformational ensembles in agreement with the four sets of RDCs. The MaxOcc analysis performed here identifies the most likely sampled region in the conformational space of the system which, strikingly, overlaps well with the structures independently sampled in the molecular dynamics calculations and even better with the RDC selected ensemble.

  3. STIFFNESS AND EXCLUDED VOLUME EFFECTS ON CONFORMATION AND DYNAMICS OF POLYMERS: A SIMULATION STUDY

    Institute of Scientific and Technical Information of China (English)

    An-bang Li; Yuan-gen Yao; Hong Xu

    2012-01-01

    This work investigates the effects of the excluded volume and especially those of the chain stiffness on the structural and dynamical properties of a model polymer chain.The theoretical framework is the same as in the recent works by Steinhauser et al.,where a Rouse approach is adopted.Our model differs in that our chains have a finite average bending angle.As in the works by Steinhauser et al.,Langevin dynamic simulations were performed without hydrodynamic interactions.Whereas this doesn't impact the static properties we obtain,it also allows us to compare our results on dynamic properties to those predicted by Rouse theory,where hydrodynamic interactions are also neglected.Our results show that the structural properties are very sensitive to the chain stiffness,whereas the dynamic scaling laws remain the same as those by Rouse theory,with the prefactor depending on the persistence length.

  4. Exploring transition pathway and free-energy profile of large-scale protein conformational change by combining normal mode analysis and umbrella sampling molecular dynamics.

    Science.gov (United States)

    Wang, Jinan; Shao, Qiang; Xu, Zhijian; Liu, Yingtao; Yang, Zhuo; Cossins, Benjamin P; Jiang, Hualiang; Chen, Kaixian; Shi, Jiye; Zhu, Weiliang

    2014-01-09

    Large-scale conformational changes of proteins are usually associated with the binding of ligands. Because the conformational changes are often related to the biological functions of proteins, understanding the molecular mechanisms of these motions and the effects of ligand binding becomes very necessary. In the present study, we use the combination of normal-mode analysis and umbrella sampling molecular dynamics simulation to delineate the atomically detailed conformational transition pathways and the associated free-energy landscapes for three well-known protein systems, viz., adenylate kinase (AdK), calmodulin (CaM), and p38α kinase in the absence and presence of respective ligands. For each protein under study, the transient conformations along the conformational transition pathway and thermodynamic observables are in agreement with experimentally and computationally determined ones. The calculated free-energy profiles reveal that AdK and CaM are intrinsically flexible in structures without obvious energy barrier, and their ligand binding shifts the equilibrium from the ligand-free to ligand-bound conformation (population shift mechanism). In contrast, the ligand binding to p38α leads to a large change in free-energy barrier (ΔΔG ≈ 7 kcal/mol), promoting the transition from DFG-in to DFG-out conformation (induced fit mechanism). Moreover, the effect of the protonation of D168 on the conformational change of p38α is also studied, which reduces the free-energy difference between the two functional states of p38α and thus further facilitates the conformational interconversion. Therefore, the present study suggests that the detailed mechanism of ligand binding and the associated conformational transition is not uniform for all kinds of proteins but correlated to their respective biological functions.

  5. Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography.

    Science.gov (United States)

    Basudhar, Debashree; Madrona, Yarrow; Kandel, Sylvie; Lampe, Jed N; Nishida, Clinton R; de Montellano, Paul R Ortiz

    2015-04-17

    Defining the conformational states of cytochrome P450 active sites is critical for the design of agents that minimize drug-drug interactions, the development of isoform-specific P450 inhibitors, and the engineering of novel oxidative catalysts. We used two-dimensional (1)H,(15)N HSQC chemical shift perturbation mapping of (15)N-labeled Phe residues and x-ray crystallography to examine the ligand-dependent conformational dynamics of CYP119. Active site Phe residues were most affected by the binding of azole inhibitors and fatty acid substrates, in agreement with active site localization of the conformational changes. This was supported by crystallography, which revealed movement of the F-G loop with various azoles. Nevertheless, the NMR chemical shift perturbations caused by azoles and substrates were distinguishable. The absence of significant chemical shift perturbations with several azoles revealed binding of ligands to an open conformation similar to that of the ligand-free state. In contrast, 4-phenylimidazole caused pronounced NMR changes involving Phe-87, Phe-144, and Phe-153 that support the closed conformation found in the crystal structure. The same closed conformation is observed by NMR and crystallography with a para-fluoro substituent on the 4-phenylimidazole, but a para-chloro or bromo substituent engendered a second closed conformation. An open conformation is thus favored in solution with many azole ligands, but para-substituted phenylimidazoles give rise to two closed conformations that depend on the size of the para-substituent. The results suggest that ligands selectively stabilize discrete cytochrome P450 conformational states.

  6. Conformational Transitions

    Science.gov (United States)

    Czerminski, Ryszard; Roitberg, Adrian; Choi, Chyung; Ulitsky, Alexander; Elber, Ron

    1991-10-01

    Two computational approaches to study plausible conformations of biological molecules and the transitions between them are presented and discussed. The first approach is a new search algorithm which enhances the sampling of alternative conformers using a mean field approximation. It is argued and demonstrated that the mean field approximation has a small effect on the location of the minima. The method is a combination of the LES protocol (Locally Enhanced Sampling) and simulated annealing. The LES method was used in the past to study the diffusion pathways of ligands from buried active sites in myoglobin and leghemoglobin to the exterior of the protein. The present formulation of LES and its implementation in a Molecular Dynamics program is described. An application for side chain placement in a tetrapeptide is presented. The computational effort associated with conformational searches using LES grows only linearly with the number of degrees of freedom, whereas in the exact case the computational effort grows exponentially. Such saving is of course associated with a mean field approximation. The second branch of studies pertains to the calculation of reaction paths in large and flexible biological systems. An extensive mapping of minima and barriers for two different tetrapeptides is calculated from the known minima and barriers of alanine tetrapeptide which we calculated recently.1 The tetrapeptides are useful models for the formation of secondary structure elements since they are the shortest possible polymers of this type which can still form a complete helical turn. The tetrapeptides are isobutyryl-val(χ1=60)-ala-ala and isobutyryl-val(χ1=-60)-ala-ala. Properties of the hundreds of minima and of the hundreds intervening barriers are discussed. Estimates for thermal transition times between the many conformers (and times to explore the complete phase space) are calculated and compared. It is suggested that the most significant effect of the side chain size is

  7. Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein.

    Science.gov (United States)

    Hao, Ge-Fei; Xu, Wei-Fang; Yang, Sheng-Gang; Yang, Guang-Fu

    2015-10-23

    Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation.

  8. Conformations, Transverse Fluctuations and Crossover Dynamics of a Semi-Flexible Chain in Two Dimensions

    CERN Document Server

    Huang, Aiqun; Binder, Kurt

    2014-01-01

    We present a unified scaling theory for the dynamics of monomers of a semiflexible chain under good solvent condition in the free draining limit. We consider both the cases where the contour length $L$ is comparable to the persistence length $\\ell_p$ and the case $L\\gg \\ell_p$. Our theory captures the early time monomer dynamics of a stiff chain characterized by $t^{3/4}$ dependence for the mean square displacement(MSD) of the monomers, but predicts a first crossover to the Rouse regime of $t^{2\

  9. Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method

    Science.gov (United States)

    2011-12-01

    and Biochemistry , U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland §Computational Sciences and Engineering Branch...of motion of a system with constraints: molecular dynamics of n- alkanes . J. Comput. Phys. 1977, 23, 327–341. (29) Feig, M.; Karanicolas, J.; Brooks, C

  10. Assignment of Side-Chain Conformation Using Adiabatic Energy Mapping, Free Energy Perturbation, and Molecular Dynamic Simulations

    DEFF Research Database (Denmark)

    Frimurer, Thomas M.; Günther, Peter H.; Sørensen, Morten Dahl

    1999-01-01

    adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)......adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)...

  11. Arc Plasma Torch Modeling

    CERN Document Server

    Trelles, J P; Vardelle, A; Heberlein, J V R

    2013-01-01

    Arc plasma torches are the primary components of various industrial thermal plasma processes involving plasma spraying, metal cutting and welding, thermal plasma CVD, metal melting and remelting, waste treatment and gas production. They are relatively simple devices whose operation implies intricate thermal, chemical, electrical, and fluid dynamics phenomena. Modeling may be used as a means to better understand the physical processes involved in their operation. This paper presents an overview of the main aspects involved in the modeling of DC arc plasma torches: the mathematical models including thermodynamic and chemical non-equilibrium models, turbulent and radiative transport, thermodynamic and transport property calculation, boundary conditions and arc reattachment models. It focuses on the conventional plasma torches used for plasma spraying that include a hot-cathode and a nozzle anode.

  12. On the dynamics of the space-charge layer inside the nozzle of a cutting torch and its relation with the ``non-destructive'' double-arcing phenomenon

    Science.gov (United States)

    Prevosto, L.; Kelly, H.; Mancinelli, B.

    2011-10-01

    Experimental observations on the plasma dynamics inside the nozzle of a 30 A oxygen cutting torch operated at conditions close to the double arcing are reported. It is employed a technique previously developed in our laboratory consisting in using the nozzle as a large-sized Langmuir probe. Based on the behavior of the ion current signal and simple estimations, it is concluded that (1) the non-equilibrium plasma inside the nozzle is far from the steady state in time, in contrast to what is frequently assumed. The power supply ripple was identified as the main fluctuations source and (2) large-scale plasma fluctuations inside the nozzle could cause transient (total duration of the order of 100 μs) Townsend avalanches developing in the space-charge layer located between the arc plasma and the nozzle wall. Such events trigger the so called non-destructive double-arcing phenomena without appealing to the presence of insulating films deposited inside the nozzle orifice, as was previously proposed in the literature.

  13. Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane

    DEFF Research Database (Denmark)

    Witzke, Sarah; Petersen, Michael; Carpenter, Timothy S.

    2016-01-01

    Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by antibiotics such as the lantibiotics, which achieve their function by disrupting...... of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes....... dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization...

  14. Application of welding science to welding engineering: A lumped parameter gas metal arc welding dynamic process model

    Energy Technology Data Exchange (ETDEWEB)

    Murray, P.E.; Smartt, H.B.; Johnson, J.A. [Lockheed Martin Idaho Technologies, Idaho Falls, ID (United States)

    1997-12-31

    We develop a model of the depth of penetration of the weld pool in gas metal arc welding (GMAW) which demonstrates interaction between the arc, filler wire and weld pool. This model is motivated by the observations of Essers and Walter which suggest a relationship between droplet momentum and penetration depth. A model of gas metal arc welding was augmented to include an improved model of mass transfer and a simple model of accelerating droplets in a plasma jet to obtain the mass and momentum of impinging droplets. The force of the droplets and depth of penetration is correlated by a dimensionless linear relation used to predict weld pool depth for a range of values of arc power and contact tip to workpiece distance. Model accuracy is examined by comparing theoretical predictions and experimental measurements of the pool depth obtained from bead on plate welds of carbon steel in an argon rich shielding gas. Moreover, theoretical predictions of pool depth are compared to the results obtained from the heat conduction model due to Christensen et al. which suggest that in some cases the momentum of impinging droplets is a better indicator of the depth of the weld pool and the presence of a deep, narrow penetration.

  15. Arc Statistics

    CERN Document Server

    Meneghetti, M; Dahle, H; Limousin, M

    2013-01-01

    The existence of an arc statistics problem was at the center of a strong debate in the last fifteen years. With the aim to clarify if the optical depth for giant gravitational arcs by galaxy clusters in the so called concordance model is compatible with observations, several studies were carried out which helped to significantly improve our knowledge of strong lensing clusters, unveiling their extremely complex internal structure. In particular, the abundance and the frequency of strong lensing events like gravitational arcs turned out to be a potentially very powerful tool to trace the structure formation. However, given the limited size of observational and theoretical data-sets, the power of arc statistics as a cosmological tool has been only minimally exploited so far. On the other hand, the last years were characterized by significant advancements in the field, and several cluster surveys that are ongoing or planned for the near future seem to have the potential to make arc statistics a competitive cosmo...

  16. Applications of hydrogen deuterium exchange (HDX for the characterization of conformational dynamics in light-activated photoreceptors

    Directory of Open Access Journals (Sweden)

    Robert eLindner

    2015-06-01

    Full Text Available Rational design of optogenetic tools is inherently linked to the understanding of photoreceptor function. Structural analysis of elements involved in signal integration in individual sensor domains provides an initial idea of their mode of operation, but understanding how local structural rearrangements eventually affect signal transmission to output domains requires inclusion of the effector regions in the characterization. However, the dynamic nature of these assemblies renders their structural analysis challenging and therefore a combination of high- and low-resolution techniques is required to appreciate functional aspects of photoreceptors.This review focuses on the potential of Hydrogen-Deuterium exchange coupled to mass spectrometry (HDX-MS for complementing the structural characterization of photoreceptors. In this respect, the ability of HDX-MS to provide information on the conformational dynamics and the possibility to address multiple functionally relevant states in solution render this methodology ideally suitable. We highlight recent examples demonstrating the potential of HDX-MS and discuss how these results can help to improve existing optogenetic systems or guide the design of novel optogenetic tools.

  17. TU-CD-304-01: FEATURED PRESENTATION and BEST IN PHYSICS (THERAPY): Trajectory Modulated Arc Therapy: Development of Novel Arc Delivery Techniques Integrating Dynamic Table Motion for Extended Volume Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Chin, E; Hoppe, R; Million, L; Loo, B; Koong, A; Xing, L; Hsu, A; Fahimian, B [Stanford University, Stanford, CA (United States); Otto, K [University of British Columbia, Vancouver, BC (Canada)

    2015-06-15

    Purpose: Integration of coordinated robotic table motion with inversely-planned arc delivery has the potential to resolve table-top delivery limitations of large-field treatments such as Total Body Irradiation (TBI), Total Lymphoid Irradiation (TLI), and Cranial-Spinal Irradiation (CSI). We formulate the foundation for Trajectory Modulated Arc Therapy (TMAT), and using Varian Developer Mode capabilities, experimentally investigate its practical implementation for such techniques. Methods: A MATLAB algorithm was developed for inverse planning optimization of the table motion, MLC positions, and gantry motion under extended-SSD geometry. To maximize the effective field size, delivery trajectories for TMAT TBI were formed with the table rotated at 270° IEC and dropped vertically to 152.5cm SSD. Preliminary testing of algorithm parameters was done through retrospective planning analysis. Robotic delivery was programmed using custom XML scripting on the TrueBeam Developer Mode platform. Final dose was calculated using the Eclipse AAA algorithm. Initial verification of delivery accuracy was measured using OSLDs on a solid water phantom of varying thickness. Results: A comparison of DVH curves demonstrated that dynamic couch motion irradiation was sufficiently approximated by static control points spaced in intervals of less than 2cm. Optimized MLC motion decreased the average lung dose to 68.5% of the prescription dose. The programmed irradiation integrating coordinated table motion was deliverable on a TrueBeam STx linac in 6.7 min. With the couch translating under an open 10cmx20cm field angled at 10°, OSLD measurements along the midline of a solid water phantom at depths of 3, 5, and 9cm were within 3% of the TPS AAA algorithm with an average deviation of 1.2%. Conclusion: A treatment planning and delivery system for Trajectory Modulated Arc Therapy of extended volumes has been established and experimentally demonstrated for TBI. Extension to other treatment

  18. Conformational flexibility in calcitonin: The dynamic properties of human and salmon calcitonin in solution

    Energy Technology Data Exchange (ETDEWEB)

    Amodeo, Pietro; Motta, Andrea; Strazzullo, Giuseppe [Istituto per la Chimica di Molecole di Interesse Biologico, Istituto Nazionale di Chimica dei sistemi Biologici del CNR (Italy); Castiglione Morelli, Maria A. [Universita della Basilicata, Dipartimento di Chimica (Italy)

    1999-02-15

    We have studied the dynamic properties of human (h) and salmon (s) calcitonin (CT) in solution. For both hormones, distance geometry in torsion-angle space has been used to generate three-dimensional structures consistent with NMR data obtained in sodium dodecyl sulfate micelles. For sCT and hCT we used, respectively, 356 and 275 interproton distances together with hydrogen-bonds as restraints. To better characterize their flexibility and dynamic properties two fully unrestrained 1100-ps molecular dynamics (MD) simulations in methanol were performed on the lowest-energy structures of both hormones. Statistical analyses of average geometric parameters and of their fluctuations performed in the last 1000 ps of the MD run show typical helical values for residues 9-19 of sCT during the whole trajectory. For hCT a shorter helix was observed involving residues 13-21, with a constant helical region in the range 13-19. Angular order parameters S({phi}) and S({psi}) indicate that hCT exhibits a higher flexibility, distributed along the whole chain, including the helix, while the only flexible amino acid residues in sCT connect three well-defined domains. Finally, our study shows that simulated annealing in torsion-angle space can efficiently be extended to NMR-based three-dimensional structure calculations of helical polypeptides. Furthermore, provided that a sufficient number of NMR restraints describes the system, the method allows the detection of equilibria in solution. This identification occurs through the generation of 'spurious' high-energy structures, which, for right-handed {alpha}-helices, are likely to be represented by left-handed {alpha}-helices.

  19. Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis.

    Science.gov (United States)

    Kanazhevskaya, Lyubov Yu; Koval, Vladimir V; Vorobjev, Yury N; Fedorova, Olga S

    2012-02-14

    Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from exposure to UV light, ionizing radiation, alkylating agents, and oxygen radicals. In human cells, AP endonuclease 1 (APE1) recognizes this mutagenic lesion and initiates its repair via a specific incision of the phosphodiester backbone 5' to the AP site. We have investigated a detailed mechanism of APE1 functioning using fluorescently labeled DNA substrates. A fluorescent adenine analogue, 2-aminopurine, was introduced into DNA substrates adjacent to the abasic site to serve as an on-site reporter of conformational transitions in DNA during the catalytic cycle. Application of a pre-steady-state stopped-flow technique allows us to observe changes in the fluorescence intensity corresponding to different stages of the process in real time. We also detected an intrinsic Trp fluorescence of the enzyme during interactions with 2-aPu-containing substrates. Our data have revealed a conformational flexibility of the abasic DNA being processed by APE1. Quantitative analysis of fluorescent traces has yielded a minimal kinetic scheme and appropriate rate constants consisting of four steps. The results obtained from stopped-flow data have shown a substantial influence of the 2-aPu base location on completion of certain reaction steps. Using detailed molecular dynamics simulations of the DNA substrates, we have attributed structural distortions of AP-DNA to realization of specific binding, effective locking, and incision of the damaged DNA. The findings allowed us to accurately discern the step that corresponds to insertion of specific APE1 amino acid residues into the abasic DNA void in the course of stabilization of the precatalytic complex.

  20. Molecular Dynamics Simulations of Ligand-Induced Flap Conformational Changes in Cathepsin-D-A Comparative Study.

    Science.gov (United States)

    Arodola, Olayide A; Soliman, Mahmoud E S

    2016-11-01

    The flap region in aspartic proteases is a unique structural feature to this class of enzymes, and found to have a profound impact on protein overall structure, function, and dynamics. Understanding the structure and dynamic behavior of the flap regions is crucial in the design of selective inhibitors against aspartic proteases. Cathepsin-D, an aspartic protease enzyme, has been implicated in a long list of degenerative diseases as well as breast cancer progression. Presented herein, for the first time, is a comprehensive description of the conformational flap dynamics of cathepsin-D using a comparative 50 ns "multiple" molecular dynamics simulations. Diverse collective metrics were proposed to accurately define flap dynamics. These are distance d1 between the flap tips residues (Gly79 and Met301); dihedral angle ϕ; in addition to TriCα angles Gly79-Asp33-Asp223, θ1 , and Gly79-Asp223-Met301, θ2 . The maximum distance attained throughout the simulation was 17.42 and 11.47 Å for apo and bound cathepsin-D, respectively, while the minimum distance observed was 8.75 and 6.32 Å for apo and bound cathepsin-D, respectively. The movement of the flap as well as the twist of the active pocket can properly be explained by measuring the angle, θ1 , between Gly79-Asp33-Met301 and correlating it with the distance Cα of the flap tip residues. The asymmetrical opening of the binding cavity was best described by the large shift of -6.26° to +20.94° in the dihedral angle, ϕ, corresponding to the full opening of the flap at a range of 31-33 ns. A wide-range of post-dynamic analyses was also applied in this report to supplement our findings. We believe that this report would augment current efforts in designing potent structure-based inhibitors against cathepsin-D in the treatment of breast cancer and other degenerative diseases. J. Cell. Biochem. 117: 2643-2657, 2016. © 2016 Wiley Periodicals, Inc.

  1. A protein dynamics study of photosystem II: the effects of protein conformation on reaction center function.

    Science.gov (United States)

    Vasil'ev, Sergej; Bruce, Doug

    2006-05-01

    Molecular dynamics simulations have been performed to study photosystem II structure and function. Structural information obtained from simulations was combined with ab initio computations of chromophore excited states. In contrast to calculations based on the x-ray structure, the molecular-dynamics-based calculations accurately predicted the experimental absorbance spectrum. In addition, our calculations correctly assigned the energy levels of reaction-center (RC) chromophores, as well as the lowest-energy antenna chlorophyll. The primary and secondary quinone electron acceptors, Q(A) and Q(B), exhibited independent changes in position over the duration of the simulation. Q(B) fluctuated between two binding sites similar to the proximal and distal sites previously observed in light- and dark-adapted RC from purple bacteria. Kinetic models were used to characterize the relative influence of chromophore geometry, site energies, and electron transport rates on RC efficiency. The fluctuating energy levels of antenna chromophores had a larger impact on quantum yield than did their relative positions. Variations in electron transport rates had the most significant effect and were sufficient to explain the experimentally observed multi-component decay of excitation in photosystem II. The implications of our results are discussed in the context of competing evolutionary selection pressures for RC structure and function.

  2. Conformal coupling associated with the Noether symmetry and its connection with the $\\Lambda$CDM dynamics

    CERN Document Server

    de Souza, Rudinei C

    2013-01-01

    The aim of the present work is to investigate a non-minimally coupled scalar field model through the Noether symmetry approach. The radiation, matter and cosmological constant eras are analyzed. By means of a change of coordinates in the configuration space generated by the Noether symmetry, the field equations can be reduced to a single equation which is of the form of the Friedmann equation for the $\\Lambda$CDM model. In this way, it is formally shown that the dynamical system can furnish solutions with the same form as those of the $\\Lambda$CDM model, although the theory here considered is physically different from the former. The conserved quantity associated with the Noether symmetry can be related to the kinetic term of the scalar field and could constrain the possible deviations of the model from the $\\Lambda$CDM picture.

  3. Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

    DEFF Research Database (Denmark)

    Goldar, A.; Arneodo, A.; Audit, B.

    2016-01-01

    We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations......, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement...... with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic...

  4. Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

    Science.gov (United States)

    Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.

    2016-03-01

    We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

  5. A molecular dynamics study of the BACE1 conformational change from Apo to closed form induced by hydroxyethylamine derived compounds.

    Science.gov (United States)

    Gueto-Tettay, Carlos; Zuchniarz, Joshua; Fortich-Seca, Yeyson; Gueto-Tettay, Luis Roberto; Drosos-Ramirez, Juan Carlos

    2016-11-01

    BACE1 is an aspartyl protease which is a therapeutic target for Alzheimer's disease (AD) because of its participation in the rate-limiting step in the production of Aβ-peptide, the accumulation of which produces senile plaques and, in turn, the neurodegenerative effects associated with AD. The active site of this protease is composed in part by two aspartic residues (Asp93 and Asp289). Additionally, the catalytic site has been found to be covered by an antiparallel hairpin loop called the flap. The dynamics of this flap are fundamental to the catalytic function of the enzyme. When BACE1 is inactive (Apo), the flap adopts an open conformation, allowing a substrate or inhibitor to access the active site. Subsequent interaction with the ligand induces flap closure and the stabilization of the macromolecular complex. Further, the protonation state of the aspartic dyad is affected by the chemical nature of the species entering the active site, so that appropriate selection of protonation states for the ligand and the catalytic residues will permit the elucidation of the inhibitory pathway for BACE1. In the present study, comparative analysis of different combinations of protonation states for the BACE1-hydroxyethylamine (HEA) system is reported. HEAs are potent inhibitors of BACE1 with favorable pharmacological and kinetic properties, as well as oral bioavailability. The results of Molecular Dynamics (MD) simulations and population density calculations using 8 different parameters demonstrate that the LnAsp289 configuration (HEA with a neutral amine and the Asp289 residue protonated) is the only one which permits the expected conformational change in BACE1, from apo to closed form, after flap closure. Additionally, differences in their capacities to establish and maintain interactions with residues such as Asp93, Gly95, Thr133, Asp289, Gly291, and Asn294 during this step allow differentiation among the inhibitory activities of the HEAs. The results and methodology here

  6. Feedback Linearization Based Arc Length Control for Gas Metal Arc Welding

    DEFF Research Database (Denmark)

    Thomsen, Jesper Sandberg

    2005-01-01

    In this paper a feedback linearization based arc length controller for gas metal arc welding (GMAW) is described. A nonlinear model describing the dynamic arc length is transformed into a system where nonlinearities can be cancelled by a nonlinear state feedback control part, and thus, leaving only...

  7. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-03-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  8. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  9. A coupling of homology modeling with multiple molecular dynamics simulation for identifying representative conformation of GPCR structures: a case study on human bombesin receptor subtype-3.

    Science.gov (United States)

    Nowroozi, Amin; Shahlaei, Mohsen

    2017-02-01

    In this study, a computational pipeline was therefore devised to overcome homology modeling (HM) bottlenecks. The coupling of HM with molecular dynamics (MD) simulation is useful in that it tackles the sampling deficiency of dynamics simulations by providing good-quality initial guesses for the native structure. Indeed, HM also relaxes the severe requirement of force fields to explore the huge conformational space of protein structures. In this study, the interaction between the human bombesin receptor subtype-3 and MK-5046 was investigated integrating HM, molecular docking, and MD simulations. To improve conformational sampling in typical MD simulations of GPCRs, as in other biomolecules, multiple trajectories with different initial conditions can be employed rather than a single long trajectory. Multiple MD simulations of human bombesin receptor subtype-3 with different initial atomic velocities are applied to sample conformations in the vicinity of the structure generated by HM. The backbone atom conformational space distribution of replicates is analyzed employing principal components analysis. As a result, the averages of structural and dynamic properties over the twenty-one trajectories differ significantly from those obtained from individual trajectories.

  10. Conformational sampling enhancement of replica exchange molecular dynamics simulations using swarm particle intelligence

    Energy Technology Data Exchange (ETDEWEB)

    Kamberaj, Hiqmet, E-mail: hkamberaj@ibu.edu.mk [Department of Computer Engineering, International Balkan University, Tashko Karadza 11A, Skopje (Macedonia, The Former Yugoslav Republic of)

    2015-09-28

    In this paper, we present a new method based on swarm particle social intelligence for use in replica exchange molecular dynamics simulations. In this method, the replicas (representing the different system configurations) are allowed communicating with each other through the individual and social knowledge, in additional to considering them as a collection of real particles interacting through the Newtonian forces. The new method is based on the modification of the equations of motion in such way that the replicas are driven towards the global energy minimum. The method was tested for the Lennard-Jones clusters of N = 4,  5, and 6 atoms. Our results showed that the new method is more efficient than the conventional replica exchange method under the same practical conditions. In particular, the new method performed better on optimizing the distribution of the replicas among the thermostats with time and, in addition, ergodic convergence is observed to be faster. We also introduce a weighted histogram analysis method allowing analyzing the data from simulations by combining data from all of the replicas and rigorously removing the inserted bias.

  11. Subdiffusion in hair bundle dynamics: The role of protein conformational fluctuations

    Science.gov (United States)

    Sharma, Rati; Cherayil, Binny J.

    2012-12-01

    The detection of sound signals in vertebrates involves a complex network of different mechano-sensory elements in the inner ear. An especially important element in this network is the hair bundle, an antenna-like array of stereocilia containing gated ion channels that operate under the control of one or more adaptation motors. Deflections of the hair bundle by sound vibrations or thermal fluctuations transiently open the ion channels, allowing the flow of ions through them, and producing an electrical signal in the process, eventually causing the sensation of hearing. Recent high frequency (0.1-10 kHz) measurements by Kozlov et al. [Proc. Natl. Acad. Sci. U.S.A. 109, 2896 (2012)], 10.1073/pnas.1121389109 of the power spectrum and the mean square displacement of the thermal fluctuations of the hair bundle suggest that in this regime the dynamics of the hair bundle are subdiffusive. This finding has been explained in terms of the simple Brownian motion of a filament connecting neighboring stereocilia (the tip link), which is modeled as a viscoelastic spring. In the present paper, the diffusive anomalies of the hair bundle are ascribed to tip link fluctuations that evolve by fractional Brownian motion, which originates in fractional Gaussian noise and is characterized by a power law memory. The predictions of this model for the power spectrum of the hair bundle and its mean square displacement are consistent with the experimental data and the known properties of the tip link.

  12. Conformational dynamics of Rouse chains during creep/recovery processes: a review

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroshi; Inoue, Tadashi [Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2005-05-18

    The Rouse model is a well-established model for non-entangled polymer chains and also serves as a fundamental model for entangled chains. The dynamic behaviour of this model under strain-controlled conditions has been fully analysed in the literature. However, despite the importance of the Rouse model, no analysis has been made so far of the orientational anisotropy of the Rouse eigenmodes during the stress-controlled, creep and recovery processes. For completeness of the analysis of the model, the Rouse equation of motion is solved to calculate this anisotropy for monodisperse chains and their binary blends during the creep/recovery processes. The calculation is simple and straightforward, but the result is intriguing in the sense that each Rouse eigenmode during these processes has a distribution in the retardation times. This behaviour, reflecting the interplay/correlation among the Rouse eigenmodes of different orders (and for different chains in the blends) under the constant stress condition, is quite different from the behaviour under rate-controlled flow (where each eigenmode exhibits retardation/relaxation associated with a single characteristic time). Furthermore, the calculation indicates that the Rouse chains exhibit affine deformation on sudden imposition/removal of the stress and the magnitude of this deformation is inversely proportional to the number of bond vectors per chain. In relation to these results, a difference between the creep and relaxation properties is also discussed for chains obeying multiple relaxation mechanisms (Rouse and reptation mechanisms). (topical review)

  13. Suture Dynamics of the Banda Arc Collision Zone: Geochemical and Age Analysis of Ultramafic and Mafic Bodies in Timor, Indonesia

    Science.gov (United States)

    Valenza, J. M.; Harris, R. A.; Spencer, C. J.; Hoiland, C. W.; Flores, J. A.

    2013-12-01

    New age and geochemical data confirm that most ultramafic bodies on the north coast of Timor are derived from the distal reaches of the Australian continental margin lower plate that was exhumed by extension during Late Paleozoic to Mesozoic rifting. The ultramafic bodies were accreted to Timor during Late Miocene to present arc-continent collision. One of the lherzolitic ultramafic bodies near Caicua was previously unknown, but yields clear isotopic indicators that it is kin to the Hili Manu mafic and ultramafic complex further to the west. Zircon grains from metagabbro of the Hili Manu complex have cores with mostly Early Permian ages and rims of Latest Miocene ages. Isotopic analysis indicates abyssal plain, or passive margin affinity of the Caicua ultramafic body. One important exception to this pattern are mafic and ultramafic bodies associated with the Ocussi volcanics, which yield Miocene and Pliocene ages and supra-subduction zone chemical signatures. The Ocussi body is clearly part of the upper plate of the collision and formed after collision initiated further to the east. It is also structurally higher than the Hili Manu complex and has no affinities with the Australian plate. This study documents that both the upper and lower plates of the active arc-continent collision contribute mafic and ultramafic rocks to the evolving suture zone between the Indo-Australian and Asian plates in the Banda Arc region.

  14. Conformational Dynamics and Proton Relay Positioning in Nickel Catalysts for Hydrogen Production and Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Franz, James A.; O' Hagan, Molly J.; Ho, Ming-Hsun; Liu, Tianbiao L.; Helm, Monte L.; Lense, Sheri; DuBois, Daniel L.; Shaw, Wendy J.; Appel, Aaron M.; Raugei, Simone; Bullock, R. Morris

    2013-12-09

    The [Ni(PR2NR’2)2]2+ catalysts, (where PR2NR´2 is 1,5-R´-3,7-R-1,5-diaza-3,7-diphosphacyclooctane), are some of the fastest reported for hydrogen production and oxidation, however, chair/boat isomerization and the presence of a fifth solvent ligand have the potential to slow catalysis by incorrectly positioning the pendant amines or blocking the addition of hydrogen. Here, we report the structural dynamics of a series of [Ni(PR2NR’2)2]n+ complexes, characterized by NMR spectroscopy and theoretical modeling. A fast exchange process was observed for the [Ni(CH3CN)(PR2NR’2)2]2+ complexes which depends on the ligand. This exchange process was identified to occur through a three step mechanism including dissociation of the acetonitrile, boat/chair isomerization of each of the four rings identified by the phosphine ligands (including nitrogen inversion), and reassociation of acetonitrile on the opposite side of the complex. The rate of the chair/boat inversion can be influenced by varying the substituent on the nitrogen atom, but the rate of the overall exchange process is at least an order of magnitude faster than the catalytic rate in acetonitrile demonstrating that the structural dynamics of the [Ni(PR2NR´2)2]2+ complexes does not hinder catalysis. This material is based upon work supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under FWP56073. Research by J.A.F., M.O., M-H. H., M.L.H, D.L.D. A.M.A., S. R. and R.M.B. was carried out in the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science. W.J.S. and S.L. were funded by the DOE Office of Science Early Career Research Program through the Office of Basic Energy Sciences. T.L. was supported by the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences

  15. Water clusters adsorbed on polycyclic aromatic hydrocarbons: Energetics and conformational dynamics

    Science.gov (United States)

    Simon, Aude; Spiegelman, Fernand

    2013-05-01

    In this work, we present some classical molecular dynamics (MD) simulations and finite temperature infrared (IR) spectra of water clusters adsorbed on coronene (C24H12), a compact polycyclic aromatic hydrocarbon (PAH). The potential energy surface is obtained within the self-consistent-charge density-functional based tight-binding approach with modifications insuring the correct description of water-water and water-PAH interactions. This scheme is benchmarked for the minimal energy structures of (C24H12)(H2O)n (n = 3-10) against density-functional theory (DFT) calculations and for the low-energy isomers of (H2O)6 and (C6H6)(H2O)3 against correlated wavefunction and DFT calculations. A detailed study of the low energy isomers of (C24H12)(H2O)3, 6 complexes is then provided. On-the-fly Born-Oppenheimer MD simulations are performed in the temperature T range 10-350 K for (C24H12)(H2O)n (n = 3-7) complexes. The description of the evolution of the systems with T is provided with emphasis on (C24H12)(H2O)n (n = 3,6). For T in the range 50-150 K, isomerisation processes are observed and when T increases, a solid-to-liquid phase-change like behavior is shown. The desorption of one water molecule is frequently observed at 300 K. The isomerisation processes are evidenced on the finite temperature IR spectra and the results are presented for (C24H12)(H2O)n (n = 3,6). A signature for the edge-coordination of the water cluster on the PAH is also proposed.

  16. Conformation change of an isotactic poly (N-isopropylacrylamide) membrane: Molecular dynamics

    Science.gov (United States)

    Adroher-Benítez, Irene; Moncho-Jordá, Arturo; Odriozola, Gerardo

    2017-05-01

    In this work, isotactic Poly (N-Isopropylacrylamide)—PNIPAM—in neat water and in electrolyte solutions is studied by means of molecular dynamics simulations. This is done for an infinitely diluted oligomer and for an assembly of several PNIPAM chains arranged into a planar membrane configuration with a core-shell morphology. We employed two different force fields, AMBER (assisted model building with energy refinement) and OPLS-AA (all atom - optimized potentials for liquid simulations) in combination with extended simple point charge water. Despite the more water insoluble character of isotactic oligomers, our results support the existence of a coil to globule transition for the isolated 30-mer. This may imply the existence of an oligomer rich phase of coil-like structures in equilibrium with a water rich phase for temperatures close but below the coil to globule transition temperature, TΘ. However, the obtained coil structure is much more compact than that corresponding to the syndiotactic chain. Our estimations of TΘ are (308 ±5 ) K and (303 ±5 ) K for AMBER and OPLS-AA, respectively. The membrane configuration allows one to include chain-chain interactions, to follow density profiles of water, polymer, and solutes, and accessing the membrane-water interface tension. Results show gradual shrinking and swelling of the membrane by switching temperature above and below TΘ, as well as the increase and decrease of the membrane-water interface tension. Finally, concentration profiles for 1M NaCl and 1M NaI electrolytes are shown, depicting a strong salting-out effect for NaCl and a much lighter effect for NaI, in good qualitative agreement with experiments.

  17. Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells

    KAUST Repository

    Kadaré, Gress

    2015-01-02

    Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule.

  18. Trapping conformational states along ligand-binding dynamics of peptide deformylase: the impact of induced fit on enzyme catalysis.

    Directory of Open Access Journals (Sweden)

    Sonia Fieulaine

    2011-05-01

    Full Text Available For several decades, molecular recognition has been considered one of the most fundamental processes in biochemistry. For enzymes, substrate binding is often coupled to conformational changes that alter the local environment of the active site to align the reactive groups for efficient catalysis and to reach the transition state. Adaptive substrate recognition is a well-known concept; however, it has been poorly characterized at a structural level because of its dynamic nature. Here, we provide a detailed mechanism for an induced-fit process at atomic resolution. We take advantage of a slow, tight binding inhibitor-enzyme system, actinonin-peptide deformylase. Crystal structures of the initial open state and final closed state were solved, as well as those of several intermediate mimics captured during the process. Ligand-induced reshaping of a hydrophobic pocket drives closure of the active site, which is finally "zipped up" by additional binding interactions. Together with biochemical analyses, these data allow a coherent reconstruction of the sequence of events leading from the encounter complex to the key-lock binding state of the enzyme. A "movie" that reconstructs this entire process can be further extrapolated to catalysis.

  19. Targeted molecular dynamics reveals overall common conformational changes upon hybrid domain swing-out in beta3 integrins.

    Science.gov (United States)

    Provasi, Davide; Murcia, Marta; Coller, Barry S; Filizola, Marta

    2009-11-01

    The beta3 integrin family members alphaIIbeta3 and alphaVbeta3 signal bidirectionally through long-range allosteric changes, including a transition from a bent unliganded-closed low-affinity state to an extended liganded-open high-affinity state. To obtain an atomic-level description of this transition in an explicit solvent, we carried out targeted molecular dynamics simulations of the headpieces of alphaIIbeta3 and alphaVbeta3 integrins. Although minor differences were observed between these receptors, our results suggest a common transition pathway in which the hybrid domain swing-out is accompanied by conformational changes within the beta3 betaA (I-like) domain that propagate through the alpha7 helix C-terminus, and are followed by the alpha7 helix downward motion and the opening of the beta6-alpha7 loop. Breaking of contact interactions between the beta6-alpha7 loop and the alpha1 helix N-terminus results in helix straightening, internal rearrangements of the specificity determining loop (SDL), movement of the beta1-alpha1 loop toward the metal ion dependent adhesion site (MIDAS), and final changes at the interfaces between the beta3 betaA (I-like) domain and either the hybrid or the alpha beta-propeller domains. Taken together, our results suggest novel testable hypotheses of intradomain and interdomain interactions responsible for beta3 integrin activation.

  20. Structural insights for designed alanine-rich helices: Comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation

    Science.gov (United States)

    Song, Kun; Stewart, James M.; Fesinmeyer, R. Matthew

    2013-01-01

    The temperature dependence of helical propensities for the peptides Ac-ZGG-(KAAAA)3X-NH2 (Z = Y or G, X = A, K, and d-Arg) were studied both experimentally and by molecular dynamics simulations. Good agreement is observed in both the absolute helical propensities as well as relative helical content along the sequence; the global minimum on the calculated free energy landscape corresponds to a single α-helical conformation running from K4 – A18 with some terminal fraying, particularly at the C-terminus. Energy component analysis shows that the single helix state has favorable intramolecular electrostatic energy due to hydrogen bonds, and that less-favorable two-helix globular states have favorable solvation energy. The central lysine residues do not appear to increase helicity; however, both experimental and simulation studies show increasing helicity in the series X = Ala → Lys → d-Arg. This C-capping preference was also experimentally confirmed in Ac-(KAAAA)3X-GY-NH2 and (KAAAA)3X-GY-NH2 sequences. The roles of the C-capping groups, and of lysines throughout the sequence, in the MD-derived ensembles are analyzed in detail. PMID:18428207

  1. Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel.

    Directory of Open Access Journals (Sweden)

    Pär Bjelkmar

    2009-02-01

    Full Text Available Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120 degrees rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation ( approximately 35 degrees of the extracellular end of all S4 segments is present also in a reference 0.5 micros simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3(10 helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4-lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros. Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane

  2. Hamming distance geometry of a protein conformational space. Application to the clustering of a 4 ns molecular dynamics trajectory of the HIV-1 integrase catalytic core

    CERN Document Server

    Laboulais, C; Le Bret, M; Gabarro-Arpa, J; Laboulais, Cyril; Ouali, Mohammed; Bret, Marc Le; Gabarro-Arpa, Jacques

    2001-01-01

    Protein structures can be encoded into binary sequences, these are used to define a Hamming distance in conformational space: the distance between two different molecular conformations is the number of different bits in their sequences. Each bit in the sequence arises from a partition of conformational space in two halves. Thus, the information encoded in the binary sequences is also used to characterize the regions of conformational space visited by the system. We apply this distance and their associated geometric structures, to the clustering and analysis of conformations sampled during a 4 ns molecular dynamics simulation of the HIV-1 integrase catalytic core. The cluster analysis of the simulation shows a division of the trajectory into two segments of 2.6 and 1.4 ns length, which are qualitatively different: the data points to the fact that equilibration is only reached at the end of the first segment. Some length of the paper is devoted to compare the Hamming distance to the r.m.s. deviation measure. Th...

  3. Hydrocarbons depending on the chain length and head group adopt different conformations within a water-soluble nanocapsule: 1H NMR and molecular dynamics studies.

    Science.gov (United States)

    Choudhury, Rajib; Barman, Arghya; Prabhakar, Rajeev; Ramamurthy, V

    2013-01-10

    In this study we have examined the conformational preference of phenyl-substituted hydrocarbons (alkanes, alkenes, and alkynes) of different chain lengths included within a confined space provided by a molecular capsule made of two host cavitands known by the trivial name "octa acid" (OA). One- and two-dimensional (1)H NMR experiments and molecular dynamics (MD) simulations were employed to probe the location and conformation of hydrocarbons within the OA capsule. In general, small hydrocarbons adopted a linear conformation while longer ones preferred a folded conformation. In addition, the extent of folding and the location of the end groups (methyl and phenyl) were dependent on the group (H(2)C-CH(2), HC═CH, and C≡C) adjacent to the phenyl group. In addition, the rotational mobility of the hydrocarbons within the capsule varied; for example, while phenylated alkanes tumbled freely, phenylated alkenes and alkynes resisted such a motion at room temperature. Combined NMR and MD simulation studies have confirmed that molecules could adopt conformations within confined spaces different from that in solution, opening opportunities to modulate chemical behavior of guest molecules.

  4. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    Science.gov (United States)

    Dai, Jin; Niemi, Antti J.; He, Jianfeng

    2016-07-01

    The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

  5. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics.

    Science.gov (United States)

    Dai, Jin; Niemi, Antti J; He, Jianfeng

    2016-07-28

    The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

  6. Quantitative conformational analysis of the core region of N-glycans using residual dipolar couplings, aqueous molecular dynamics, and steric alignment

    Energy Technology Data Exchange (ETDEWEB)

    Almond, Andrew; Duus, Jens O. [Carlsberg Laboratory (Denmark)

    2001-08-15

    A method is described for quantitatively investigating the dynamic conformation of small oligosaccharides containing an {alpha}(1{sup {yields}}6) linkage. It was applied to the oligosaccharide Man-{alpha}(1{sup {yields}}3) {l_brace}Man-{alpha} (1{sup {yields}}6){r_brace}Man-{alpha}-O-Me, which is a core region frequently observed in N-linked glycans. The approach tests an aqueous molecular dynamics simulation, capable of predicting microscopic dynamics, against experimental residual dipolar couplings, by assuming that alignment is caused purely by steric hindrance. The experimental constraints were heteronuclear and homonuclear residual dipolar couplings, and in particular those within the {alpha}(1{sup {yields}}6) linkage itself. Powerful spin-state-selective pulse sequences and editing schemes were used to obtain the most relevant couplings for testing the model. Molecular dynamics simulations in water over a period of 50 ns were not able to predict the correct rotamer population at the {alpha}(1{sup {yields}}6) linkage to agree with the experimental data. However, this sampling problem could be corrected using a simple maximum likelihood optimisation, indicating that the simulation was modelling local dynamics correctly. The maximum likelihood prediction of the residual dipolar couplings was found to be an almost equal population of the gg and gt rotamer conformations at the {alpha}(1{sup {yields}}6) linkage, and the tg conformation was predicted to be unstable and unpopulated in aqueous solution. In this case all twelve measured residual dipolar couplings could be satisfied. This conformer population could also be used to make predictions of scalar couplings with the use of a previously derived empirical equation, and is qualitatively in agreement with previous predictions based on NMR, X-ray crystallography and optical data.

  7. CyberArc: a non-coplanar-arc optimization algorithm for CyberKnife

    Science.gov (United States)

    Kearney, Vasant; Cheung, Joey P.; McGuinness, Christopher; Solberg, Timothy D.

    2017-07-01

    The goal of this study is to demonstrate the feasibility of a novel non-coplanar-arc optimization algorithm (CyberArc). This method aims to reduce the delivery time of conventional CyberKnife treatments by allowing for continuous beam delivery. CyberArc uses a 4 step optimization strategy, in which nodes, beams, and collimator sizes are determined, source trajectories are calculated, intermediate radiation models are generated, and final monitor units are calculated, for the continuous radiation source model. The dosimetric results as well as the time reduction factors for CyberArc are presented for 7 prostate and 2 brain cases. The dosimetric quality of the CyberArc plans are evaluated using conformity index, heterogeneity index, local confined normalized-mutual-information, and various clinically relevant dosimetric parameters. The results indicate that the CyberArc algorithm dramatically reduces the treatment time of CyberKnife plans while simultaneously preserving the dosimetric quality of the original plans.

  8. Sorting of LPXTG peptides by archetypal sortase A: role of invariant substrate residues in modulating the enzyme dynamics and conformational signature of a productive substrate.

    Science.gov (United States)

    Biswas, Tora; Pawale, Vijaykumar S; Choudhury, Devapriya; Roy, Rajendra P

    2014-04-22

    Transpeptidase sortase catalyzes the covalent anchoring of surface proteins to the cell wall in Gram-positive bacteria. Sortase A (SrtA) of Staphylococcus aureus is a prototype enzyme and considered a bona fide drug target because several substrate proteins are virulence-related and implicated in pathogenesis. Besides, SrtA also works as a versatile tool in protein engineering. Surface proteins destined for cell wall anchoring contain a LPXTG sequence located in their C-terminus which serves as a substrate recognition motif for SrtA. Recent studies have implicated substrate-induced conformational dynamics in SrtA. In the present work, we have explored the roles of invariant Leu and Pro residues of the substrate in modulating the enzyme dynamics with a view to understand the selection process of a catalytically competent substrate. Overall results of molecular dynamics simulations and experiments carried out with noncanonical substrates and site-directed mutagenesis reveal that the kinked conformation due to Pro in LPXTG is obligatory for productive binding but does not per se control the enzyme dynamics. The Leu residue of the substrate appears to play the crucial role of an anchor to the beta6-beta7 loop directing the conformational transition of the enzyme from an "open" to a "closed" state subsequent to which the Pro residue facilitates the consummation of binding through predominant engagement of the loop and catalytic motif residues in hydrophobic interactions. Collectively, our study provides insights about specificity, tolerance, and conformational sorting of substrate by SrtA. These results have important implications in designing newer substrates and inhibitors for this multifaceted enzyme.

  9. Molecular Dynamics Investigations of the Local Structural Characteristics of DNA Oligonucleotides: Studies of Helical Axis Deformations, Conformational Sequence Dependence and Modified Nucleoside Perturbations.

    Science.gov (United States)

    Louise-May, Shirley

    The present DNA studies investigate the local structure of DNA oligonucleotides in order to characterize helical axis deformations, sequence dependent fine structure and modified nucleoside perturbations of selected oligonucleotide sequences. The molecular dynamics method is used to generate an ensemble of energetically feasible DNA conformations which can then be analyzed for dynamical conformational properties, some of which can be compared to experimentally derived values. A theory and graphical presentation for the analysis of helical deformations of DNA based on the configurational statistics of polymers, called "Persistence Analysis", was designed. The results of the analysis on prototype forms, static crystal structures and two solvated MD simulations of the sequence d(CGCGAATTCGCG) indicate that all of the expected features of bending can be sensitively and systematically identified by this approach. Comparison of the relative performance of three molecular dynamics potential functions commonly used for dynamical modeling of biological macromolecules; CHARMm, AMBER and GROMOS was investigated via in vacuo MD simulations on the dodecamer sequence d(CGCGAATTCGCG)_2 with respect to the conformational properties of each dynamical model and their ability to support A and B families of DNA. Vacuum molecular dynamics simulations using the CHARMm force field carried out on simple homo- and heteropolymers of DNA led to the conclusion that sequence dependent fine structure appears to be well defined for adenine-thymine rich sequences both at the base pair and base step level whereas much of the the fine structure found in cytosine -guanine rich sequences appears to be context dependent. The local conformational properties of the homopolymer poly (dA) -poly (dT) revealed one dynamical model which was found in general agreement with fiber models currently available. Investigation of the relative structural static and dynamical effect of the misincorporation of

  10. Application of time series analysis on molecular dynamics simulations of proteins: A study of different conformational spaces by principal component analysis

    Science.gov (United States)

    Alakent, Burak; Doruker, Pemra; Camurdan, Mehmet C.

    2004-09-01

    Time series analysis is applied on the collective coordinates obtained from principal component analysis of independent molecular dynamics simulations of α-amylase inhibitor tendamistat and immunity protein of colicin E7 based on the Cα coordinates history. Even though the principal component directions obtained for each run are considerably different, the dynamics information obtained from these runs are surprisingly similar in terms of time series models and parameters. There are two main differences in the dynamics of the two proteins: the higher density of low frequencies and the larger step sizes for the interminima motions of colicin E7 than those of α-amylase inhibitor, which may be attributed to the higher number of residues of colicin E7 and/or the structural differences of the two proteins. The cumulative density function of the low frequencies in each run conforms to the expectations from the normal mode analysis. When different runs of α-amylase inhibitor are projected on the same set of eigenvectors, it is found that principal components obtained from a certain conformational region of a protein has a moderate explanation power in other conformational regions and the local minima are similar to a certain extent, while the height of the energy barriers in between the minima significantly change. As a final remark, time series analysis tools are further exploited in this study with the motive of explaining the equilibrium fluctuations of proteins.

  11. Modeling rf breakdown arcs

    CERN Document Server

    Insepov, Zeke; Huang, Dazhang; Mahalingam, Sudhakar; Veitzer, Seth

    2010-01-01

    We describe breakdown in 805 MHz rf accelerator cavities in terms of a number of mechanisms. We devide the breakdown process into three stages: (1) we model surface failure using molecular dynamics of fracture caused by electrostatic tensile stress, (2) we model the ionization of neutrals responsible for plasma initiation and plasma growth using a particle in cell code, and (3) we model surface damage by assuming a process similar to unipolar arcing. Although unipolar arcs are strictly defined with equipotential boundaries, we find that the cold, dense plasma in contact with the surface produces very small Debye lengths and very high electric fields over a large area. These high fields produce strong erosion mechanisms, primarily self sputtering, compatible with the crater formation that we see. Results from the plasma simulation are included as a guide to experimental verification of this model.

  12. Water drives peptide conformational transitions

    CERN Document Server

    Nerukh, Dmitry

    2011-01-01

    Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that water is the main driving force of the conformational changes.

  13. Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis

    Science.gov (United States)

    Chen, Jianzhong; Wang, Jinan; Zhu, Weiliang

    2016-11-01

    More and more researchers are interested in and focused on how a limited repertoire of antibodies can bind and correspondingly protect against an almost limitless diversity of invading antigens. In this work, a series of 200-ns molecular dynamics (MD) simulations followed by principal component (PC) analysis and free energy calculations were performed to probe potential mechanism of conformational diversity of antibody SPE7. The results show that the motion direction of loops H3 and L3 is different relative to each other, implying that a big structural difference exists between these two loops. The calculated energy landscapes suggest that the changes in the backbone angles ψ and φ of H-Y101 and H-Y105 provide significant contributions to the conformational diversity of SPE7. The dihedral angle analyses based on MD trajectories show that the side-chain conformational changes of several key residues H-W33, H-Y105, L-Y34 and L-W93 around binding site of SPE7 play a key role in the conformational diversity of SPE7, which gives a reasonable explanation for potential mechanism of cross-reactivity of single antibody toward multiple antigens.

  14. Arc Jet Testing of Thermal Protection Materials: 3 Case Studies

    Science.gov (United States)

    Johnson, Sylvia; Conley, Joe

    2015-01-01

    Arc jet testing is used to simulate entry to test thermal protection materials. This paper discusses the usefulness of arc jet testing for 3 cases. Case 1 is MSL and PICA, Case 2 is Advanced TUFROC, and Case 3 is conformable ablators.

  15. Transportation Conformity

    Science.gov (United States)

    This section provides information on: current laws, regulations and guidance, policy and technical guidance, project-level conformity, general information, contacts and training, adequacy review of SIP submissions

  16. Group Cohesiveness, Deviation, Stress, and Conformity

    Science.gov (United States)

    1993-08-11

    Yuke1son, Weinberg & Jackson , 1984; Carron & Chelladurai, 1981). The classical studies of jury dynamics began to appear within the field of...1987), individuation was negatively correlated with conformity (Santee & Maslach , 1982). Conformity Paradi&ms Host studies of conformity have...appear to affect conformity rates independently of attraction . However, later ~tudies by Dittes and Kelley (1956) and Jackson and Saltzstein (1958

  17. Arcing Model of a Disconnector and its Effect on VFTO

    Science.gov (United States)

    Lin, Xin; Wang, Na; Xu, Jianyuan

    2013-07-01

    In the computational process of very fast transient over-voltage (VFTO), it is essential to find an accurate model for a gas insulated substation. The arcing model of the disconnector is particularly important. The general arcing model is not able to give a good description of the arc development process. In this paper, based on the physical process of arcing and existing arc models (the exponential time-varying resistance model and the segmental arcing models), a dynamic arcing model is proposed, which is divided into two stages before and after the zero crossing. The dynamic arcing model combines hyperbola time-varying resistance and the Mayr model to describe the dynamic process of arcing. The present paper creates an arc model blockset upon the Matlab/Simulink software platform. Moreover for a specific 1100 kV station, VFTO is simulated in detail based on different arcing models. It is demonstrated that the dynamic arcing model can describe the physical arc process precisely and is useful for improving the accuracy of VFTO simulations.

  18. Conformational and entropy analyses of extended molecular dynamics simulations of α-, β- and γ-cyclodextrins and of the β-cyclodextrin/nabumetone complex.

    Science.gov (United States)

    Suárez, Dimas; Díaz, Natalia

    2017-01-04

    Herein, we report the results of 5.0 μs molecular dynamics simulations of native α-, β- and γ-cyclodextrins (CDs) in explicit water solvent that are useful to describe, in a comparative manner, the distorted geometry of the CD molecules in aqueous solution, the width and fluctuations of their cavities, and the number of cavity waters. By discretizing the time evolution of the dihedral angles, the rate of conformational change of the torsional motions and the conformational entropy are calculated for the three CDs, thus allowing the analysis of the extent of the MD sampling and the entropic significance of the CD flexibility. To obtain a first estimation of the conformational and entropy changes in the host molecule upon ligand binding, the inclusion complex formed between β-CD and nabumetone is also studied. Overall, the simulations complement previous experimental results on the structure and dynamics of native CDs, and together with the results obtained for the inclusion complex, provide insight into the entropic effects at work on the binding equilibria between CDs and guest ligands.

  19. Conformational dynamics of a hydrophobic prion fragment (113-127) in different pH and osmolyte solutions.

    Science.gov (United States)

    Inayathullah, Mohammed; Rajadas, Jayakumar

    2016-06-01

    Prion diseases are characterized by a conformational change in prion protein from its native state into beta-sheet rich aggregates that are neurotoxic. The central domain that contain a highly conserved hydrophobic region of the protein play an important role in the toxicity. The conformation of the proteins is largely influenced by various solvent environments. Here we report results of study of hydrophobic prion fragment peptide PrP(113-127) under different pH and osmolytes solution conditions. The secondary structure and the folding of PrP(113-127) was determined using circular dichroism and fluorescence spectroscopic methods. The results indicate that PrP(113-127) adopts a random coil conformation in aqueous buffer at neutral pH and that converted into beta sheet on aging. Even though the initial random coil conformation was similar in different pH conditions, the acidic as well as basic pH conditions delays the conformational transition to beta sheet. FRET results indicate that the distance between N and C-terminal regions increased on aging due to unfolding by self-assembly of the peptide into an organized beta sheet structure. Presence of osmolytes, prevented or decelerated the aggregation process of PrP(113-127) peptide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Dynamic MLC tracking of moving targets with a single kV imager for 3D conformal and IMRT treatments

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Per R. (Dept. of Oncology, Aarhus Univ. Hospital (Denmark)), E-mail: perpolse@rm.dk; Cho, Byungchul; Sawant, Amit; Ruan, Dan; Keall, Paul J. (Dept. of Radiation Oncology, Stanford Univ., Stanford (United States))

    2010-10-15

    Background. Tumor motion during radiotherapy is a major challenge for accurate dose delivery, in particular for hypofractionation and dose painting. The motion may be compensated by dynamic multileaf collimator (DMLC) tracking. Previous work has demonstrated that a single kV imager can accurately localize moving targets for DMLC tracking during rotational delivery, however this method has not been investigated for the static gantry geometry used for conformal and IMRT treatments. In this study we investigate the accuracy of single kV-imager based DMLC tracking for static-gantry delivery. Material and methods. A 5-field treatment plan with circular field shape and 200 MU per field was delivered in 20 s per field to a moving phantom with an embedded gold marker. Fluoroscopic kV images were acquired at 5 Hz perpendicular to the treatment beam axis during a 120 deg pre-treatment gantry rotation, during treatment delivery, and during inter-field gantry rotations. The three-dimensional marker position was estimated from the kV images and used for MLC adaptation. Experiments included 12 thoracic/abdominal tumor trajectories and five prostate trajectories selected from databases with 160 and 548 trajectories, respectively. The tracking error was determined as the mismatch between the marker position and the MLC aperture center in portal images. Simulations extended the study to all trajectories in the databases and to treatments with prolonged duration of 60 s per field. Results. In the experiments, the mean root-mean-square (rms) tracking error was 0.9 mm (perpendicular to MLC) and 1.1 mm (parallel to MLC) for thoracic/abdominal tumor trajectories and 0.6 mm (perpendicular) and 0.5 mm (parallel) for prostate trajectories. Simulations of these experiments agreed to within 0.1 mm. Simulations of all trajectories in the databases resulted in mean rms tracking errors of 0.6 mm (perpendicular) and 0.9 mm (parallel) for thorax/abdomen tumors and 0.4 mm (perpendicular) and 0

  1. Comparison of 2D and 3D modeled tumor motion estimation/prediction for dynamic tumor tracking during arc radiotherapy

    Science.gov (United States)

    Liu, Wu; Ma, Xiangyu; Yan, Huagang; Chen, Zhe; Nath, Ravinder; Li, Haiyun

    2017-05-01

    Many real-time imaging techniques have been developed to localize a target in 3D space or in a 2D beam’s eye view (BEV) plane for intrafraction motion tracking in radiation therapy. With tracking system latency, the 3D-modeled method is expected to be more accurate even in terms of 2D BEV tracking error. No quantitative analysis, however, has been reported. In this study, we simulated co-planar arc deliveries using respiratory motion data acquired from 42 patients to quantitatively compare the accuracy between 2D BEV and 3D-modeled tracking in arc therapy and to determine whether 3D information is needed for motion tracking. We used our previously developed low kV dose adaptive MV-kV imaging and motion compensation framework as a representative of 3D-modeled methods. It optimizes the balance between additional kV imaging dose and 3D tracking accuracy and solves the MLC blockage issue. With simulated Gaussian marker detection errors (zero mean and 0.39 mm standard deviation) and ~155/310/460 ms tracking system latencies, the mean percentage of time that the target moved  >2 mm from the predicted 2D BEV position are 1.1%/4.0%/7.8% and 1.3%/5.8%/11.6% for the 3D-modeled and 2D-only tracking, respectively. The corresponding average BEV RMS errors are 0.67/0.90/1.13 mm and 0.79/1.10/1.37 mm. Compared to the 2D method, the 3D method reduced the average RMS unresolved motion along the beam direction from ~3 mm to ~1 mm, resulting in on average only  <1% dosimetric advantage in the depth direction. Only for a small fraction of the patients, when tracking latency is long, the 3D-modeled method showed significant improvement of BEV tracking accuracy, indicating potential dosimetric advantage. However, if the tracking latency is short (~150 ms or less), those improvements are limited. Therefore, 2D BEV tracking has sufficient targeting accuracy for most clinical cases. The 3D technique is, however, still important in solving the MLC blockage problem

  2. Continuous wave W- and D-Band EPR spectroscopy offer “sweet-spots” for characterizing conformational changes and dynamics in intrinsically disordered proteins

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Thomas M.; Liu, Zhanglong; Esquiaqui, Jackie M.; Pirman, Natasha L.; Milshteyn, Eugene; Fanucci, Gail E., E-mail: fanucci@chem.ufl.edu

    2014-07-18

    Highlights: • W- and D-Band line shapes are sensitive to motions in the 0.1–2 ns time regime. • These frequencies effectively report on conformational dynamics of IDPs. • W-band spectra reflecting helical formation in IA{sub 3} is experimentally demonstrated. - Abstract: Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy is a powerful tool for characterizing conformational sampling and dynamics in biological macromolecules. Here we demonstrate that nitroxide spectra collected at frequencies higher than X-band (∼9.5 GHz) have sensitivity to the timescale of motion sampled by highly dynamic intrinsically disordered proteins (IDPs). The 68 amino acid protein IA{sub 3}, was spin-labeled at two distinct sites and a comparison of X-band, Q-band (35 GHz) and W-band (95 GHz) spectra are shown for this protein as it undergoes the helical transition chemically induced by tri-fluoroethanol. Experimental spectra at W-band showed pronounced line shape dispersion corresponding to a change in correlation time from ∼0.3 ns (unstructured) to ∼0.6 ns (α-helical) as indicated by comparison with simulations. Experimental and simulated spectra at X- and Q-bands showed minimal dispersion over this range, illustrating the utility of SDSL EPR at higher frequencies for characterizing structural transitions and dynamics in IDPs.

  3. Optical diagnostics of a gliding arc

    DEFF Research Database (Denmark)

    Sun, Z.W.; Zhu, J.J.; Li, Z.S.;

    2013-01-01

    Dynamic processes in a gliding arc plasma generated between two diverging electrodes in ambient air driven by 31.25 kHz AC voltage were investigated using spatially and temporally resolved optical techniques. The life cycles of the gliding arc were tracked in fast movies using a high-speed camera...

  4. VP40 of the Ebola Virus as a Target for EboV Therapy: Comprehensive Conformational and Inhibitor Binding Landscape from Accelerated Molecular Dynamics.

    Science.gov (United States)

    Balmith, Marissa; Soliman, Mahmoud E S

    2017-03-01

    The first account of the dynamic features of the loop region of VP40 of the Ebola virus was studied using accelerated molecular dynamics simulations and reported herein. Among the proteins of the Ebola virus, the matrix protein (VP40) plays a significant role in the virus lifecycle thereby making it a promising therapeutic target. Of interest is the newly elucidated N-terminal domain loop region of VP40 comprising residues K127, T129, and N130 which when mutated to alanine have demonstrated an unrecognized role for N-terminal domain-plasma membrane interaction for efficient VP40-plasma membrane localization, oligomerization, matrix assembly, and egress. The molecular understanding of the conformational features of VP40 in complex with a known inhibitor still remains elusive. Using accelerated molecular dynamics approaches, we conducted a comparative study on VP40 apo and bound systems to understand the conformational features of VP40 at the molecular level and to determine the effect of inhibitor binding with the aid of a number of post-dynamic analytical tools. Significant features were seen in the presence of an inhibitor as per molecular mechanics/generalized born surface area binding free energy calculations. Results revealed that inhibitor binding to VP40 reduces the flexibility and mobility of the protein as supported by root mean square fluctuation and root mean square deviation calculations. The study revealed a characteristic "twisting" motion and coiling of the loop region of VP40 accompanied by conformational changes in the dimer interface upon inhibitor binding. We believe that results presented in this study will ultimately provide useful insight into the binding landscape of VP40 which could assist researchers in the discovery of potent Ebola virus inhibitors for anti-Ebola therapies.

  5. Workers’ Conformism

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2013-10-01

    Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

  6. Use of simulation models to study the dynamic of recall of non-conform perishable produce through the supply chain

    DEFF Research Database (Denmark)

    Busato, P.; Sopegno, A.; Berruto, R.

    2013-01-01

    together to form a large size lot at some points in the supply-chain. Larger lot size could imply higher risk for the consumers in case of recall of the produce and much higher recall time and cost for the supply-chain. When a non-conformity occurs, the time to recall the produce depends on many factors...

  7. Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Youngjoo; Kim, Dong Kyun [School of Pharmacy, Sungkyunkwan University, Suwon (Korea, Republic of); Seo, Min-Duk [College of Pharmacy & Department of Molecular Science and Technology, Ajou University, Suwon (Korea, Republic of); Kim, Kyeong-Man [College of Pharmacy, Chonnam National University, Gwang-Ju (Korea, Republic of); Chung, Ka Young, E-mail: kychung2@skku.edu [School of Pharmacy, Sungkyunkwan University, Suwon (Korea, Republic of)

    2015-01-30

    Highlights: • The conformational dynamics of β-arrestin1 or β-arrestin2 were analyzed by HDX-MS. • β-Strands II through IV were more dynamic in β-arrestin2 than in β-arrestin1. • The middle loop was less dynamic in β-arrestin2 than in β-arrestin1. • Upon pre-activation by the R169E mutation, β-arrestins became more dynamic. • Pre-activation affected a wider region of β-arrestin1 compared to β-arrestin2. - Abstract: Arrestins have important roles in G protein-coupled receptor (GPCR) signaling including desensitization of GPCRs and G protein-independent signaling. There have been four arrestins identified: arrestin1, arrestin2 (e.g. β-arrestin1), arrestin3 (e.g. β-arrestin2), and arrestin4. β-Arrestin1 and β-arrestin2 are ubiquitously expressed and regulate a broad range of GPCRs, while arrestin1 and arrestin4 are expressed in the visual system. Although the functions of β-arrestin1 and β-arrestin2 widely overlap, β-arrestin2 has broader receptor selectivity, and a few studies have suggested that β-arrestin1 and β-arrestin2 have distinct cellular functions. Here, we compared the conformational dynamics of β-arrestin1 and β-arrestin2 by hydrogen/deuterium exchange mass spectrometry (HDX-MS). We also used the R169E mutant as a pre-activation model system. HDX-MS data revealed that β-strands II through IV were more dynamic in β-arrestin2 in the basal state, while the middle loop was more dynamic in β-arrestin1. With pre-activation, both β-arrestin1 and β-arrestin2 became more flexible, but broader regions of β-arrestin1 became flexible compared to β-arrestin2. The conformational differences between β-arrestin1 and β-arrestin2 in both the basal and pre-activated states might determine their different receptor selectivities and different cellular functions.

  8. Ligand-dependent conformations and dynamics of the serotonin 5-HT(2A receptor determine its activation and membrane-driven oligomerization properties.

    Directory of Open Access Journals (Sweden)

    Jufang Shan

    Full Text Available From computational simulations of a serotonin 2A receptor (5-HT(2AR model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011, we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i-the involvement of cholesterol in the activation of the 5-HT(2AR, and (ii-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization.

  9. Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood-brain barrier.

    Science.gov (United States)

    Duarte, João M N; Gruetter, Rolf

    2012-05-01

    Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics.

  10. TH-C-12A-09: Planning and Delivery of the Fully Dynamic Trajectory Modulated Arc Therapy: Application to Accelerated Partial Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Liang, J; Atwood, T; Fahimian, B; Chin, E; Hristov, D [Department of Radiation Oncology, Stanford University, CA (United States); Otto, K [Department of Physics, University of British Columbia, BC (Canada)

    2014-06-15

    Purpose: A novel trajectory modulated arc therapy (TMAT) system was developed that uses source motion trajectory involving synchronized gantry rotation with translational and rotational couch movement. MLC motion and dose rate were fully optimized for dynamic beam delivery. This work presents a platform for planning deliverable TMAT on a collision free coronal trajectory and evaluates its benefit for accelerated partial breast irradiation (APBI) in a prone position. Methods: The TMAT algorithm was built on VMAT with modifications (physical properties on couch movement were defined) and enhancements (pencil beam dose calculation engine to support extended SSDs) to make it feasible for TMAT delivery. A Matlab software environment for TMAT optimization and dose calculation was created to allow any user specified motion axis. TMAT delivery was implemented on Varian TrueBeamTM STx via XML scripts. 10 prone breast irradiation cases were evaluated in VMAT and compared with a 6- field non-coplanar IMRT plan. Patient selection/exclusion criteria and structure contouring followed the guidelines of NSABP B-39/RTOG 0413 protocol. Results: TMAT delivery time was ∼4.5 minutes. 251.5°±7.88° of non-isocentric couch arc was achieved by the optimized trajectory with 180– 210 control points at 1°–2° couch increments. The improved dose distribution by TMAT was most clearly observed by the marked reduction in the volume of irradiated normal breast tissue in the high dose region. The ratios of the normal breast tissue volume receiving more than 50%, 80% and 100% of the prescription dose for TMAT versus IMRT were: V50%(TMAT/IMRT) = 78.38%±13.03%, V80%(TMAT/IMRT) = 44.19%±9.04% and V100% (TMAT/IMRT) = 9.96%±7.55%, all p≤0.01. Conclusion: The study is the first demonstration of planning and delivery implementation of a fully dynamic APBI TMAT system with continuous couch motion. TMAT achieved significantly improved dosimetry over noncoplanar IMRT on dose volume parameters

  11. Dynamics and structural changes induced by ATP and/or substrate binding in the inward-facing conformation state of P-glycoprotein

    Science.gov (United States)

    Watanabe, Yurika; Hsu, Wei-Lin; Chiba, Shuntaro; Hayashi, Tomohiko; Furuta, Tadaomi; Sakurai, Minoru

    2013-02-01

    P-glycoprotein (P-gp) is a multidrug transporter that catalyzes the transport of a substrate. To elucidate the underlying mechanism of this type of substrate transport, we performed molecular dynamics (MD) simulations using the X-ray crystal structure of P-gp, which has an inward-facing conformation. Our simulations indicated that the dimerization of the nucleotide binding domains (NBDs) is driven by the binding of ATP to the NBDs and/or the binding of the substrate to a cavity in the transmembrane domains (TMDs). Based on these results, we discuss a role of ATP in the allosteric communication that occurs between the NBDs and the TMDs.

  12. Dynamic stability of a curved pipe bent in the arc of a circle on hinge supports at the ends

    Indian Academy of Sciences (India)

    D S Lolov; S V Lilkova-Markova

    2006-10-01

    Curved pipes conveying fluids are investigated in the paper. Methods of numerical solution of the dynamic stability of a pipe in its plane are developed. An example of a curved pipe is solved by these methods. A non-dimensional parameter of flow velocity and a non-dimensional circular frequency are obtained.

  13. 宫颈癌术后快速旋转调强放疗和三维适形放疗计划的对比研究%RapidArc radiotherapy for postoperative cervical cancer: comparison with three-dimensional conformal radiotherapy

    Institute of Scientific and Technical Information of China (English)

    蒋军; 李莉; 张利文; 廖珊; 黄荣

    2013-01-01

    Objective To compare the differences of dose distribution in clinical target volume and organ at risk (OAR) between volumetric-modulated arc therapy(RapidArc) and conventional three-dimensional conformal radiotherapy (3D-CRT) in the radiotherapy of postoperative cervical cancer.Methods Ten postoperative patients with cervical cancer were chosen randomly.The next steps were CT scan,PTV and OAR contouring.The RapidArc plan and 3D-CRT plan were performed for each patient with the prescribed dose 50Gy,respectively.Homogeneity index (HI),conformity index (CI),maximum dose (PTVmax),minimum dose (PTVmin),mean dose(PTVmean) of PTV and irradiated volume of OARs were calculated and the results were compared.Results Conformity index (CI) of PTV and PTV Dmean in RapidArc plan were better than those in 3D-CRT plan with statistically significant difference (P < 0.05).Compared with 3D-CRT plans,V20 of the left and right femoral head,V50 of the bladder and V40,V50 of rectumin RapidArc plans all reduced and the differences were statistically significant (P < 0.05).While there were no significant difference on the PTV Dmax,PTV Dmin,HI and OARs(V10,V20,V30,V40,V50 of the small bowel,V10,V20,V30 of the rectum,V1o,V20,V30,V40 of the bladder,V10,V30,V40,V50 of the left and right femoral head) between 3D-CRT and RapidArc group (P > 0.05).Conclusion RapidArc plans are better than 3D-CRT plans in CI of PTV and PTV Dmean in the radiotherapy of postoperative cervical cancer.Meanwhile,compared with 3D-CRT plans,there are more advantages in sparing the OAR in RapidArc plans.%目的 探讨宫颈癌术后快速旋转调强放疗(RapidArc)和三维适形放疗(3D-CRT)计划靶区及其周围危及器官(0AR)受照剂量的差异.方法 随机选择10例宫颈癌术后患者,进行CT扫描、靶区(PTV)和OAR的勾画,处方剂量50Gy.分别进行RapidArc和3D-CRT计划设计,计算并比较两种计划的PTV剂量均匀度指数(HI)、适形度指数(CI)、最大受照剂量(PTV Dmax

  14. Correlating excipient effects on conformational and storage stability of an IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry.

    Science.gov (United States)

    Manikwar, Prakash; Majumdar, Ranajoy; Hickey, John M; Thakkar, Santosh V; Samra, Hardeep S; Sathish, Hasige A; Bishop, Steven M; Middaugh, C Russell; Weis, David D; Volkin, David B

    2013-07-01

    The effects of sucrose and arginine on the conformational and storage stability of an IgG1 monoclonal antibody (mAb) were monitored by differential scanning calorimetry (DSC) and size-exclusion chromatography (SEC), respectively. Excipient effects on protein physical stability were then compared with their effects on the local flexibility of the mAb in solution at pH 6, 25°C using hydrogen/deuterium-exchange mass spectrometry (H/D-MS). Compared with a 0.1 M NaCl control, sucrose (0.5 M) increased conformational stability (T(m) values), slowed the rate of monomer loss, reduced the formation of insoluble aggregates, and resulted in a global trend of small decreases in local flexibility across most regions of the mAb. In contrast, the addition of arginine (0.5 M) decreased the mAb's conformational stability, increased the rate of loss of monomer with elevated levels of soluble and insoluble aggregates, and led to significant increases in the local flexibility in specific regions of the mAb, most notably within the constant domain 2 of the heavy chain (C(H)2). These results provide new insights into the effect of sucrose and arginine on the local dynamics of IgG1 domains as well as preliminary correlations between local flexibility within specific segments of the C(H)2 domain (notably heavy chain 241-251) and the mAb's overall physical stability.

  15. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2000-08-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, ``conformal infinity'' is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  16. Conformal Infinity

    Science.gov (United States)

    Frauendiener, Jörg

    2004-12-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  17. General Conformity

    Science.gov (United States)

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  18. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2004-01-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  19. Numerical Study on Arc Plasma Behavior During Arc Commutation Process in Direct Current Circuit Breaker

    Institute of Scientific and Technical Information of China (English)

    杨飞; 马瑞光; 吴翊; 孙昊; 纽春萍; 荣命哲

    2012-01-01

    This paper focuses on the numerical investigation of arc plasma behavior during arc commutation process in a medium-voltage direct current circuit breaker (DCCB) contact system. A three-dimensional magneto-hydrodynamic (MHD) model of air arc plasma in the contact system of a DCCB is developed, based on commercial software FLUENT. Coupled electromagnetic and gas dynamic interactions are considered as usual, and a thin layer of nonlinear electrical resistance elements is used to represent the voltage drop of plasma sheath and the formation of new arc root. The distributions of pressure, temperature, gas flow and current density of arc plasma in arc region are calculated. The simulation results indicate that the pressure distribution related to the contact system has a strong effect on the arc commutation process, arising from the change of electrical conductivity in the arc root region. In DCCB contact system, the pressure of arc root region will be concentrated and higher if the space above the moving contact is enclosed, which is not good for arc root commutation. However, when the region is opened, the pressure distribution would be lower and more evenly, which is favorable for the arc root commutation.

  20. Contralog: a Prolog conform forward-chaining environment and its application for dynamic programming and natural language parsing

    Directory of Open Access Journals (Sweden)

    Kilián Imre

    2016-06-01

    Full Text Available The backward-chaining inference strategy of Prolog is inefficient for a number of problems. The article proposes Contralog: a Prolog-conform, forward-chaining language and an inference engine that is implemented as a preprocessor-compiler to Prolog. The target model is Prolog, which ensures mutual switching from Contralog to Prolog and back. The Contralog compiler is implemented using Prolog's de facto standardized macro expansion capability. The article goes into details regarding the target model.

  1. Conformational sampling techniques.

    Science.gov (United States)

    Hatfield, Marcus P D; Lovas, Sándor

    2014-01-01

    The potential energy hyper-surface of a protein relates the potential energy of the protein to its conformational space. This surface is useful in determining the native conformation of a protein or in examining a statistical-mechanical ensemble of structures (canonical ensemble). In determining the potential energy hyper-surface of a protein three aspects must be considered; reducing the degrees of freedom, a method to determine the energy of each conformation and a method to sample the conformational space. For reducing the degrees of freedom the choice of solvent, coarse graining, constraining degrees of freedom and periodic boundary conditions are discussed. The use of quantum mechanics versus molecular mechanics and the choice of force fields are also discussed, as well as the sampling of the conformational space through deterministic and heuristic approaches. Deterministic methods include knowledge-based statistical methods, rotamer libraries, homology modeling, the build-up method, self-consistent electrostatic field, deformation methods, tree-based elimination and eigenvector following routines. The heuristic methods include Monte Carlo chain growing, energy minimizations, metropolis monte carlo and molecular dynamics. In addition, various methods to enhance the conformational search including the deformation or smoothing of the surface, scaling of system parameters, and multi copy searching are also discussed.

  2. The Effect of Flattening Filter Free on Three-dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT) Plans for Metastatic Brain Tumors from Non-small Cell Lung Cancer.

    Science.gov (United States)

    Shi, Li-Wan; Lai, You-Qun; Lin, Qin; Ha, Hui-Ming; Fu, Li-Rong

    2015-07-01

    Flattening filter free (FFF) may affect outcome measures of radiotherapy. The objective of this study is to compare the dosimetric parameters in three types of radiotherapy plans, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), with or without the flattening filter (FF), developed for the treatment of metastatic brain tumors from non-small cell lung cancer (NSCLC). From July 2013 to October 2013, 3D-CRT, IMRT, and VMAT treatment plans were designed using 6 MV and 10 MV, with and without FF, for 10 patients with brain metastasis from NSCLC. The evaluation of the treatment plans included homogeneity index (HI), conformity index (CI), monitor units (MU), mean dose (Dmean), treatment time, and the influence of FFF on volumes. There was no difference in CI or HI between FFF and FF models with 3D-CRT, IMRT, and VMAT plans. At 6 MV, a lower Dmean was seen in the FFF model of 3D-CRT and in the VMAT plan at 10 MV. In the IMRT 6 MV, IMRT 10 MV, and VMAT 10 MV plans, higher MUs were seen in the FFF models. FFF treatments are similar in quality to FF plans, generally lead to more monitor units, and are associated with shorter treatment times. FFF plans ranked by the order of superiority in terms of a time advantage are VMAT, 3D-CRT, and IMRT.

  3. What a Difference an OH Makes: Conformational Dynamics as the Basis for the Ligand Specificity of the Neomycin-Sensing Riboswitch.

    Science.gov (United States)

    Duchardt-Ferner, Elke; Gottstein-Schmidtke, Sina R; Weigand, Julia E; Ohlenschläger, Oliver; Wurm, Jan-Philip; Hammann, Christian; Suess, Beatrix; Wöhnert, Jens

    2016-01-22

    To ensure appropriate metabolic regulation, riboswitches must discriminate efficiently between their target ligands and chemically similar molecules that are also present in the cell. A remarkable example of efficient ligand discrimination is a synthetic neomycin-sensing riboswitch. Paromomycin, which differs from neomycin only by the substitution of a single amino group with a hydroxy group, also binds but does not flip the riboswitch. Interestingly, the solution structures of the two riboswitch-ligand complexes are virtually identical. In this work, we demonstrate that the local loss of key intermolecular interactions at the substitution site is translated through a defined network of intramolecular interactions into global changes in RNA conformational dynamics. The remarkable specificity of this riboswitch is thus based on structural dynamics rather than static structural differences. In this respect, the neomycin riboswitch is a model for many of its natural counterparts.

  4. An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase

    Science.gov (United States)

    Matthes, Dirk; Gapsys, Vytautas; Brennecke, Julian T.; de Groot, Bert L.

    2016-09-01

    The formation of well-defined filamentous amyloid structures involves a polydisperse collection of oligomeric states for which relatively little is known in terms of structural organization. Here we use extensive, unbiased explicit solvent molecular dynamics (MD) simulations to investigate the structural and dynamical features of oligomeric aggregates formed by a number of highly amyloidogenic peptides at atomistic resolution on the μs time scale. A consensus approach has been adopted to analyse the simulations in multiple force fields, yielding an in-depth characterization of pre-fibrillar oligomers and their global and local structure properties. A collision cross section analysis revealed structurally heterogeneous aggregate ensembles for the individual oligomeric states that lack a single defined quaternary structure during the pre-nucleation phase. To gain insight into the conformational space sampled in early aggregates, we probed their substructure and found emerging β-sheet subunit layers and a multitude of ordered intermolecular β-structure motifs with growing aggregate size. Among those, anti-parallel out-of-register β-strands compatible with toxic β-barrel oligomers were particularly prevalent already in smaller aggregates and formed prior to ordered fibrillar structure elements. Notably, also distinct fibril-like conformations emerged in the oligomeric state and underscore the notion that pre-nucleated oligomers serve as a critical intermediate step on-pathway to fibrils.

  5. Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

    Science.gov (United States)

    Ratnaparkhi, Aditi; Muthu, Shivani A; Shiriskar, Sonali M; Pissurlenkar, Raghuvir R S; Choudhary, Sinjan; Ahmad, Basir

    2015-09-01

    Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences.

  6. The conformational dynamics of H2-H3n and S2-H6 in gating ligand entry into the buried binding cavity of vitamin D receptor

    Science.gov (United States)

    Tee, Wei-Ven; Ripen, Adiratna Mat; Mohamad, Saharuddin Bin

    2016-01-01

    Crystal structures of holo vitamin D receptor (VDR) revealed a canonical conformation in which the ligand is entrapped in a hydrophobic cavity buried in the ligand-binding domain (LBD). The mousetrap model postulates that helix 12 is positioned away from the domain to expose the interior cavity. However, the extended form of helix 12 is likely due to artifacts during crystallization. In this study, we set out to investigate conformational dynamics of apo VDR using molecular dynamics simulation on microsecond timescale. Here we show the neighboring backbones of helix 2-helix 3n and beta strand 2-helix 6 of LBD, instead of the helix 12, undergo large-scale motion, possibly gating the entrance of ligand to the ligand binding domain. Docking analysis to the simulated open structure of VDR with the estimated free energy of −37.0 kJ/mol, would emphasise the role of H2-H3n and S2-H6 in facilitating the entrance of calcitriol to the LBD of VDR. PMID:27786277

  7. Conformational analysis of processivity clamps in solution demonstrates that tertiary structure does not correlate with protein dynamics.

    Science.gov (United States)

    Fang, Jing; Nevin, Philip; Kairys, Visvaldas; Venclovas, Ceslovas; Engen, John R; Beuning, Penny J

    2014-04-08

    The relationship between protein sequence, structure, and dynamics has been elusive. Here, we report a comprehensive analysis using an in-solution experimental approach to study how the conservation of tertiary structure correlates with protein dynamics. Hydrogen exchange measurements of eight processivity clamp proteins from different species revealed that, despite highly similar three-dimensional structures, clamp proteins display a wide range of dynamic behavior. Differences were apparent both for structurally similar domains within proteins and for corresponding domains of different proteins. Several of the clamps contained regions that underwent local unfolding with different half-lives. We also observed a conserved pattern of alternating dynamics of the α helices lining the inner pore of the clamps as well as a correlation between dynamics and the number of salt bridges in these α helices. Our observations reveal that tertiary structure and dynamics are not directly correlated and that primary structure plays an important role in dynamics.

  8. Gas arc constriction for plasma arc welding

    Science.gov (United States)

    McGee, William F. (Inventor); Rybicki, Daniel J. (Inventor)

    1994-01-01

    A welding torch for plasma arc welding apparatus has an inert gas applied circumferentially about the arc column externally of the constricting nozzle so as to apply a constricting force on the arc after it has exited the nozzle orifice and downstream of the auxiliary shielding gas. The constricting inert gas is supplied to a plenum chamber about the body of the torch and exits through a series of circumferentially disposed orifices in an annular wall forming a closure at the forward end of the constricting gas plenum chamber. The constricting force of the circumferential gas flow about the arc concentrates and focuses the arc column into a more narrow and dense column of energy after exiting the nozzle orifice so that the arc better retains its energy density prior to contacting the workpiece.

  9. Structural and mechanistic insight into substrate binding from the conformational dynamics in apo and substrate-bound DapE enzyme.

    Science.gov (United States)

    Dutta, Debodyuti; Mishra, Sabyashachi

    2016-01-21

    Conformational dynamics in large biomolecular systems is often associated with their physiological roles. The dynamics of a dimeric microbial enzyme, DapE, with great potential as an antibiotic target, has been studied employing long molecular dynamics simulations of the enzyme in apo form and in substrate bound complex form. The essential dynamics of the apo enzyme and the enzyme-substrate complex are extracted from the principal component analysis of the simulations of these two systems where the first two principal components are analyzed in detail. The essential motion of the enzyme in the substrate bound form exhibits a folding motion of its two catalytic domains over the two dimerization domains, which results in repulsion of water molecules away from the active site of the enzyme-substrate complex. This folding motion also leads to a stabilizing binding free energy of the substrate arising from the favorable interaction of the substrate and side chains of the enzyme. The dynamics in the enzyme-substrate complex results in stronger interaction between the catalytic and dimerization domains reflected by an increased number of inter-domain hydrogen bonds. The substrate, located in the catalytic domain of DapE, establishes contacts with the side chains of the dimerization domain of DapE by extended chains of hydrogen bonds, which emphasizes the role of the dimerization domain in substrate binding.

  10. Simulation of the Effects of Several Factors on Arc Plasma Behavior in Low Voltage Circuit Breaker

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Taking into account the properties of the arc plasma and the electromagnetic, heat and radiative phenomena, commercial computational fluid dynamics software PHOENICS has been adapted and modified to develop the three-dimensional magneto-hydrodynamic (MHD)model of arc in a low voltage circuit breaker. The effects of the arc ignition location, venting size and gassing material on arc behavior have been investigated. The analysis of the results show that the arc velocity accelerates with the increase in the distance between arc ignition location and of the venting size, and the existence of the gassing material is beneficial to improving the arc voltage and reducing the arc temperature.

  11. Non-coplanar volumetric-modulated arc therapy (VMAT) for craniopharyngiomas reduces radiation doses to the bilateral hippocampus: A planning study comparing dynamic conformal arc therapy, coplanar VMAT, and non-coplanar VMAT

    OpenAIRE

    Uto, Megumi; Mizowaki, Takashi; OGURA, KENGO; Hiraoka, Masahiro

    2016-01-01

    Background Recent studies suggest that radiation-induced injuries to the hippocampus play important roles in compromising neurocognitive functioning for patients with brain tumors and it could be important to spare the hippocampus using modern planning methods for patients with craniopharyngiomas. As bilateral hippocampus are located on the same level as the planning target volume (PTV) in patients with craniopharyngioma, it seems possible to reduce doses to hippocampus using non-coplanar bea...

  12. Use of simulation models to study the dynamic of recall of non-conform perishable produce through the supply chain

    DEFF Research Database (Denmark)

    Busato, P.; Sopegno, A.; Berruto, R.

    2013-01-01

    together to form a large size lot at some points in the supply-chain. Larger lot size could imply higher risk for the consumers in case of recall of the produce and much higher recall time and cost for the supply-chain. When a non-conformity occurs, the time to recall the produce depends on many factors...... the consumer. Each of these is a system itself that interacts with the other components of the supply-chain. The nonconformity could occur in each of these links. Because of processing plant requirement, storage requirements, and because of savings in the traceability process, often small size lots are merged...

  13. Oligosaccharides from the 3-linked 2-sulfated alpha-L-fucan and alpha-L-galactan show similar conformations but different dynamics.

    Science.gov (United States)

    Queiroz, Ismael N L; Vilela-Silva, Ana-Cristina E S; Pomin, Vitor H

    2016-11-01

    Here we have performed an nuclear magnetic resonance-based study on the ring and chain conformations as well as dynamics of oligosaccharides generated by acid hydrolysis on two structurally related glycans, a 3-linked 2-sulfated alpha-L-galactan and a 3-linked 2-sulfated alpha-L-fucan. Results derived from scalar couplings have confirmed the (1)C4 chair configuration to both alpha-L-fucose and alpha-L-galactose, and a similar solution 3D structure for the oligosaccharide chains of both sulfated glycans as seen on the basis of NOE patterns. Measurements of spin-relaxation rates have suggested, however, a slight difference dynamical property to these glycans. The fucose-based oligosaccharides showed an enhanced dynamical property if compared to the galactose-based oligosaccharides of same anomericity, sugar configuration, glycosidic bond and sulfation type. This distinction solely on the dynamical aspect has been driven therefore by the different sugar composition of the two studied sulfated glycans. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

    Energy Technology Data Exchange (ETDEWEB)

    Yi, B; Xu, H; Mutaf, Y; Prado, K [Univ. of Maryland School Of Medicine, Baltimore, MD (United States)

    2015-06-15

    Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speed of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.

  15. Lattice Monte-Carlo study of pre-conformal dynamics in strongly flavoured QCD in the light of the chiral phase transition at finite temperature

    CERN Document Server

    Miura, Kohtaroh

    2012-01-01

    We study the thermal phase transition in colour SU(3) Quantum Chromodynamics (QCD) with a variable number of fermions in the fundamental representation by using lattice Monte-Carlo simulations. We collect the (pseudo) critical couplings for N_f=(0, 4, 6,8), and we investigate the pre-conformal dynamics associated with the infra-red fixed point in terms of the N_f dependence of the transition temperature. We propose three independent estimates of the number of flavour N_f^* where the conformal phase would emerge, which give consistent results within the largish errors. We consider lines of fixed N_t in the space of (N_f, bare lattice coupling), and locate the vanishing of the step scaling function for N_f^*\\sim 11.1\\pm 1.6. We define a typical interaction strength (g_TC) at the scale of critical temperature T_c, and we find that g_TC meets the zero temperature critical couplings estimated by the two-loop Schwinger Dyson equation or the IRFP coupling in the four-loop beta-function at N_f^*\\sim 12.5\\pm 0.7. Furt...

  16. Structural insight into epothilones antitumor activity based on the conformational preferences and tubulin binding modes of epothilones A and B obtained from molecular dynamics simulations.

    Science.gov (United States)

    Jiménez, Verónica A; Alderete, Joel B; Navarrete, Karen R

    2015-01-01

    Molecular dynamics simulations were employed to analyze the conformational preferences and binding modes of epothilones A and B as a source of structural information regarding the antitumor properties of these species. Our results suggest that the conformation of free and tubulin-bound epothilones is strongly influenced by the presence of a methyl group at C12 and that epothilones A and B exploit the binding cavity in a unique and different way. The binding sites of epothilones A and B share a common region of association (Leu215, Leu217, His227, Leu228, Ala231, Phe270, Gly360, and Leu361), but lead to different ligand-residue interactions. Average interaction energies predict a larger stabilization for the epothilone B-tubulin complex, which is mainly driven by the enhancement of the electrostatic component of ligand-residue interactions compared to the epothilone A-tubulin complex. These structural and energetic results can be useful to account for the activity difference between epothilones A and B, and to design more active and potent analogs that resemble the mechanism of action of epothilones against cancer cells.

  17. Conformational studies by dynamic NMR. 88.(1) stereomutation processes in the diastereoisomers of a representative amino alcohol and related amide precursors.

    Science.gov (United States)

    Bartoli, Giuseppe; Grilli, Stefano; Lunazzi, Lodovico; Massaccesi, Massimo; Mazzanti, Andrea; Rinaldi, Samuele

    2002-04-19

    The barriers for three internal motions (i.e., phenyl and tert-butyl rotation as well as N-inversion) have been determined by dynamic NMR spectroscopy in the two diastereoisomeric forms of a typical amino alcohol [dimethylamino-2,4,4-trimethyl-3-phenyl-3-pentanol, Me(2)NCH(2)CHMeC(OH)PhBu(t)]. The two structures were assigned by connection with those of the corresponding amide precursors determined by single-crystal X-ray diffraction. These amides (C=O in place of CH(2)) too were found to undertake internal motions amenable to NMR observation, i.e., phenyl, tert-butyl, and N-CO rotations: the corresponding barriers were also measured. Ab initio computations indicate that H-bonding makes all these molecules adopt six-membered cyclic conformations, a conclusion which agrees well with the X-ray crystal structure determined for the amide precursors.

  18. Comparison study of intensity modulated arc therapy using single or multiple arcs to intensity modulated radiation therapy for high-risk prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ashamalla, Hani; Tejwani, Ajay; Parameritis, Loannis; Swamy, Uma; Luo, Pei Ching; Guirguis, Adel; Lavaf, Amir [Weill Medical College of Cornell University, Brooklyn, NY (United States)

    2013-06-15

    Intensity modulated arc therapy (IMAT) is a form of intensity modulated radiation therapy (IMRT) that delivers dose in single or multiple arcs. We compared IMRT plans versus single-arc field (1ARC) and multi-arc fields (3ARC) IMAT plans in high-risk prostate cancer. Sixteen patients were studied. Prostate (PTV{sub P}), right pelvic (PTV{sub RtLN}) and left pelvic lymph nodes (PTV{sub LtLN}), and organs at risk were contoured. PTVP, PTV{sub RtLN}, and PTV{sub LtLN} received 50.40 Gy followed by a boost to PTV{sub B} of 28.80 Gy. Three plans were per patient generated: IMRT, 1ARC, and 3ARC. We recorded the dose to the PTV, the mean dose (D{sub MEAN}) to the organs at risk, and volume covered by the 50% isodose. Efficiency was evaluated by monitor units (MU) and beam on time (BOT). Conformity index (CI), Paddick gradient index, and homogeneity index (HI) were also calculated. Average Radiation Therapy Oncology Group CI was 1.17, 1.20, and 1.15 for IMRT, 1ARC, and 3ARC, respectively. The plans' HI were within 1% of each other. The D{sub MEAN} of bladder was within 2% of each other. The rectum D{sub MEAN} in IMRT plans was 10% lower dose than the arc plans (p < 0.0001). The GI of the 3ARC was superior to IMRT by 27.4% (p = 0.006). The average MU was highest in the IMRT plans (1686) versus 1ARC (575) versus 3ARC (1079). The average BOT was 6 minutes for IMRT compared to 1.3 and 2.9 for 1ARC and 3ARC IMAT (p < 0.05). For high-risk prostate cancer, IMAT may offer a favorable dose gradient profile, conformity, MU and BOT compared to IMRT.

  19. Multiple internal reflectance infrared spectra of variably hydrated hemoglobin and myoglobin films: effects of globin hydration on ligand conformer dynamics and reactivity at the heme.

    Science.gov (United States)

    Brown, W E; Sutcliffe, J W; Pulsinelli, P D

    1983-06-07

    Multiple internal reflectance infrared (IR) spectra are reported for variably hydrated films (1.2-0.1 g of H2O/g of protein) of the carbon monoxy and oxy forms of human Hb and sperm whale Mb. The spectra show that even the limited removal of liquid and icelike hydration constraints at the globin surface is sufficient to cause a dramatic, but completely reversible, shift toward a normally minute population of sterically unhindered, linear-perpendicular, Fe-CO conformer modes (nu CO = 1968-1967 cm-1), and the destabilization of distally hindered, tilted (or bent), Fe-CO modes (nu CO = 1951, 1944-1933 cm-1). Corroborative evidence from IR band broadening trends [delta delta nu 1/2 (1968, 1967 cm-1) approximately 2-4 cm-1], corresponding changes in the visible, and H-D exchange kinetics confirm that the shift toward 1968-1967 cm-1 results in a more open distal heme pocket configuration and that it is also accompanied by a buildup of deoxy-like steric hindrance proximal to the heme. Denaturation effects are eliminated as a potential cause of the shifts, as are specific protein-protein, ion-protein, intersubunit, and MIR crystal-film surface interactions. The hydration effect exhibits globin-dependent and ligand-dependent differences, which highlight the intrinsic importance of distal steric effects within the heme pocket and their dynamic coupling with exterior solvent constraints. CO-photodissociation and O2-exchange experiments conducted on rapidly interconverting (coupled and fully hydrated) and noninterconverting (uncoupled and partially hydrated) Fe-CO conformers also suggest that the open linear-perpendicular mode corresponds to a more tightly bound form of CO than the axially distorted Fe-CO species; similar differences are not evident in Fe-O2, which already prefers a bent end-on geometry within the heme pocket. Control IR spectra aimed at monitoring the progressive effects of various denaturants on HbCO further indicate that this same open mode serves as a

  20. Rapid magmatic processes accompany arc-continent collision: the Western Bismarck arc, Papua New Guinea

    Science.gov (United States)

    Cunningham, Heather; Gill, Jim; Turner, Simon; Caulfield, John; Edwards, Louise; Day, Simon

    2012-11-01

    New U-Th-Ra, major and trace element, and Sr-Nd-Pb isotope data are presented for young lavas from the New Britain and Western Bismarck arcs in Papua New Guinea. New Britain is an oceanic arc, whereas the latter is the site of an arc-continent collision. Building on a recent study of the Manus Basin, contrasts between the two arcs are used to evaluate the processes and timescales of magma generation accompanying arc-continent collision and possible slab detachment. All three suites share many attributes characteristic of arc lavas that can be ascribed to the addition of a regionally uniform subduction component derived from the subducting altered oceanic crust and sediment followed by dynamic melting of the modified mantle. However, the Western Bismarck arc lavas diverge from the Pb isotope mixing array formed by the New Britain and the Manus Basin lavas toward elevated 208Pb/204Pb. We interpret this to reflect a second and subsequent addition of sediment melt at crustal depth during collision. 238U and 226Ra excesses are preserved in all of the lavas and are greatest in the Western Bismarck arc. High-Mg andesites with high Sr/Y ratios in the westernmost arc are attributed to recent shallow mantle flux melting at the slab edge. Data for two historical rhyolites are also presented. Although these rhyolites formed in quite different tectonic settings and display different geochemical and isotopic compositions, both formed from mafic parents within millennia.

  1. Characterization of the conformational space of a triple-stranded beta-sheet forming peptide with molecular dynamics simulations

    NARCIS (Netherlands)

    Soto, P; Colombo, G

    2004-01-01

    Molecular dynamics (MD) simulations have been performed on a series of mutants of the 20 amino acid peptide Betanova in order to critically assess the ability of MD simulations to reproduce the folding and stability of small beta-sheet-forming peptides on currently accessible timescales. Simulations

  2. An Arc in Saturn's G Ring

    Science.gov (United States)

    Burns, Joseph A.; Hedman, M.; Tiscareno, M.; Porco, C.; Jones, G.; Roussos, E.; Krupp, N.

    2006-09-01

    The G ring is a narrow, faint ring located between the orbits of Janus and Mimas. Approximately 4000 km wide, it has a strongly asymmetric brightness profile with a sharp inner edge between 167,000 km and 168,000 km from Saturn's center and a more diffuse outer part. In Cassini images, a portion of the ring contains a bright arc that abuts the G-ring's inner edge and extends over 30 degrees in longitude. By tracking this arc over the first two years of the Cassini Mission, we find its orbital period is 0.80813 day, corresponding to a semi-major axis of 167,496 km. Since this location places the arc within 6 km of the Mimas 7:6 Co-rotation Eccentricity Resonance and within 12 km of the Mimas 7:6 Inner Lindblad Resonance, the arc is likely confined in longitude by Mimas just as Neptune's ring arcs are held in place by Galatea. The arc's longitude relative to Mimas is consistent with this model. Cassini now has the opportunity to study the dynamics of this sort of system in detail over a period of years. The arc, which may be the debris of a fragmented moon, may also supply the particles found in the rest of the G ring; micron-sized grains drift outwards by non-gravitational processes in this region. The G-ring is responsible for a broad, relatively modest decrease in the fluxes of magnetospheric charged particles. When Cassini passed over the G ring in the vicinity of the arc, on September 5, 2005, the MIMI instrument detected a particularly sharp and deep charged particle absorption signature. Such a pronounced charged particle absorption was not seen in the other G-ring passages that occurred longitudinally far from the arc. The nature of this absorption provides constraints on the population of large particles in this arc.

  3. Characteristics of Atmospheric Pressure Rotating Gliding Arc Plasmas

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hao; ZHU Fengsen; TU Xin; BO Zheng; CEN Kefa; LI Xiaodong

    2016-01-01

    In this work,a novel direct current (DC) atmospheric pressure rotating gliding arc (RGA) plasma reactor has been developed for plasma-assisted chemical reactions.The influence of the gas composition and the gas flow rate on the arc dynamic behaviour and the formation of reactive species in the N2 and air gliding arc plasmas has been investigated by means of electrical signals,high speed photography,and optical emission spectroscopic diagnostics.Compared to conventional gliding arc reactors with knife-shaped electrodes which generally require a high flow rate (e.g.,10-20 L/min) to maintain a long arc length and reasonable plasma discharge zone,in this RGA system,a lower gas flow rate (e.g.,2 L/min) can also generate a larger effective plasma reaction zone with a longer arc length for chemical reactions.Two different motion patterns can be clearly observed in the N2 and air RGA plasmas.The time-resolved arc voltage signals show that three different arc dynamic modes,the arc restrike mode,takeover mode,and combined modes,can be clearly identified in the RGA plasmas.The occurrence of different motion and arc dynamic modes is strongly dependent on the composition of the working gas and gas flow rate.

  4. Characteristics of Atmospheric Pressure Rotating Gliding Arc Plasmas

    Science.gov (United States)

    Zhang, Hao; Zhu, Fengsen; Tu, Xin; Bo, Zheng; Cen, Kefa; Li, Xiaodong

    2016-05-01

    In this work, a novel direct current (DC) atmospheric pressure rotating gliding arc (RGA) plasma reactor has been developed for plasma-assisted chemical reactions. The influence of the gas composition and the gas flow rate on the arc dynamic behaviour and the formation of reactive species in the N2 and air gliding arc plasmas has been investigated by means of electrical signals, high speed photography, and optical emission spectroscopic diagnostics. Compared to conventional gliding arc reactors with knife-shaped electrodes which generally require a high flow rate (e.g., 10-20 L/min) to maintain a long arc length and reasonable plasma discharge zone, in this RGA system, a lower gas flow rate (e.g., 2 L/min) can also generate a larger effective plasma reaction zone with a longer arc length for chemical reactions. Two different motion patterns can be clearly observed in the N2 and air RGA plasmas. The time-resolved arc voltage signals show that three different arc dynamic modes, the arc restrike mode, takeover mode, and combined modes, can be clearly identified in the RGA plasmas. The occurrence of different motion and arc dynamic modes is strongly dependent on the composition of the working gas and gas flow rate. supported by National Natural Science Foundation of China (No. 51576174), the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20120101110099) and the Fundamental Research Funds for the Central Universities (No. 2015FZA4011)

  5. Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel

    DEFF Research Database (Denmark)

    Bjelkmar, Pär; Niemelä, Perttu S; Vattulainen, Ilpo;

    2009-01-01

    Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how...... transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements...... process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions...

  6. Hotspot mutations in KIT receptor differentially modulate its allosterically coupled conformational dynamics: impact on activation and drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Isaure Chauvot de Beauchêne

    2014-07-01

    Full Text Available Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D localized in crucial regulatory segments, the juxtamembrane region (JMR and the activation (A- loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations. The mutational outcomes predicted in silico were correlated with in vitro and in vivo activation rates and drug sensitivities of KIT mutants. The allosteric regulation of KIT in the native and mutated forms is described in terms of communication between the two remote segments, JMR and A-loop. A strong correlation between the communication profile and the structural and dynamical features of KIT in the native and mutated forms was established. Our results provide new insight on the determinants of receptor KIT constitutive activation by mutations and resistance of KIT mutants to inhibitors. Depiction of an intra-molecular component of the communication network constitutes a first step towards an integrated description of vast communication pathways established by KIT in physiopathological contexts.

  7. Discharge Characteristics of DC Arc Water Plasma for Environmental Applications

    Institute of Scientific and Technical Information of China (English)

    LI Tianming; Sooseok CHOI; Takayuki WATANABE

    2012-01-01

    A water plasma was generated by DC arc discharge with a hafnium embedded rodtype cathode and a nozzle-type anode. The discharge characteristics were examined by changing the operation parameter of the arc current. The dynamic behavior of the arc discharge led to significant fluctuations in the arc voltage and its frequency. Analyses of the high speed image and the arc voltage waveform showed that the arc discharge was in the restrike mode and its frequency varied within several tens of kilohertz according to the operating conditions. The larger thermal plasma volume was generated by the higher flow from the forming steam with a higher restrike frequency in the higher arc current conditions. In addition, the characteristics of the water plasma jet were investigated by means of optical emission spectroscopy to identify the abundant radicals required in an efficient waste treatment process.

  8. Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site [v2; ref status: indexed, http://f1000r.es/3pc

    Directory of Open Access Journals (Sweden)

    Kate A. Stafford

    2014-06-01

    Full Text Available Ribonuclease H1 (RNase H enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and may primarily be imposed by the distinctive RNase H protein fold.

  9. Low molecular weight oligomers of amyloid peptides display β-barrel conformations: A replica exchange molecular dynamics study in explicit solvent

    Science.gov (United States)

    De Simone, Alfonso; Derreumaux, Philippe

    2010-04-01

    The self-assembly of proteins and peptides into amyloid fibrils is connected to over 40 pathological conditions including neurodegenerative diseases and systemic amyloidosis. Diffusible, low molecular weight protein and peptide oligomers that form in the early steps of aggregation appear to be the harmful cytotoxic species in the molecular etiology of these diseases. So far, the structural characterization of these oligomers has remained elusive owing to their transient and dynamic features. We here address, by means of full atomistic replica exchange molecular dynamics simulations, the energy landscape of heptamers of the amyloidogenic peptide NHVTLSQ from the beta-2 microglobulin protein. The simulations totaling 5 μs show that low molecular weight oligomers in explicit solvent consist of β-barrels in equilibrium with amorphous states and fibril-like assemblies. The results, also accounting for the influence of the pH on the conformational properties, provide a strong evidence of the formation of transient β-barrel assemblies in the early aggregation steps of amyloid-forming systems. Our findings are discussed in terms of oligomers cytotoxicity.

  10. Single Arc VMAT of H&N cancer

    DEFF Research Database (Denmark)

    Bertelsen, Anders

      Background: A few radiation treatment planning systems are currently able to plan volumetric modulated arc therapy (VMAT). The VMAT algorithm in Pinnacle3 TM is called SmartArc. The capability of SmartArc to generate complex treatment plans for the head and neck (H&N) region was tested...... - when corrected for offset in output - satisfied a gamma criterion of 3mm and 3% of 2Gy compared to 99.7±0.1% for IMRT.   Conclusion: SmartArc generated single arc VMAT plans with improved target coverage and sparing of OARs compared to IMRT. The conformity was increased by VMAT compared to IMRT...... reducing high dose volumes in normal tissues. The VMAT plans used fewer MUs compared to the IMRT plans and reduced the treatment time by approximately 40% compared to IMRT. Both IMRT and VMAT radiation treatment plans delivered on an Elekta Synergy accelerator produced clinically acceptable geometric dose...

  11. Comparative study of two box H/ACA ribonucleoprotein pseudouridine-synthases: relation between conformational dynamics of the guide RNA, enzyme assembly and activity.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Fourmann

    Full Text Available Multiple RNA-guided pseudouridine synthases, H/ACA ribonucleoprotein particles (RNPs which contain a guide RNA and four proteins, catalyze site-specific post-transcriptional isomerization of uridines into pseudouridines in substrate RNAs. In archaeal particles, the guide small RNA (sRNA is anchored by the pseudouridine synthase aCBF5 and the ribosomal protein L7Ae. Protein aNOP10 interacts with both aCBF5 and L7Ae. The fourth protein, aGAR1, interacts with aCBF5 and enhances catalytic efficiency. Here, we compared the features of two H/ACA sRNAs, Pab21 and Pab91, from Pyrococcus abyssi. We found that aCBF5 binds much more weakly to Pab91 than to Pab21. Surprisingly, the Pab91 sRNP exhibits a higher catalytic efficiency than the Pab21 sRNP. We thus investigated the molecular basis of the differential efficiencies observed for the assembly and catalytic activity of the two enzymes. For this, we compared profiles of the extent of lead-induced cleavages in these sRNAs during a stepwise reconstitution of the sRNPs, and analyzed the impact of the absence of the aNOP10-L7Ae interaction. Such probing experiments indicated that the sRNAs undergo a series of conformational changes upon RNP assembly. These changes were also evaluated directly by circular dichroism (CD spectroscopy, a tool highly adapted to analyzing RNA conformational dynamics. In addition, our results reveal that the conformation of helix P1 formed at the base of the H/ACA sRNAs is optimized in Pab21 for efficient aCBF5 binding and RNP assembly. Moreover, P1 swapping improved the assembly of the Pab91 sRNP. Nonetheless, efficient aCBF5 binding probably also relies on the pseudouridylation pocket which is not optimized for high activity in the case of Pab21.

  12. Comparative study of two box H/ACA ribonucleoprotein pseudouridine-synthases: relation between conformational dynamics of the guide RNA, enzyme assembly and activity.

    Science.gov (United States)

    Fourmann, Jean-Baptiste; Tillault, Anne-Sophie; Blaud, Magali; Leclerc, Fabrice; Branlant, Christiane; Charpentier, Bruno

    2013-01-01

    Multiple RNA-guided pseudouridine synthases, H/ACA ribonucleoprotein particles (RNPs) which contain a guide RNA and four proteins, catalyze site-specific post-transcriptional isomerization of uridines into pseudouridines in substrate RNAs. In archaeal particles, the guide small RNA (sRNA) is anchored by the pseudouridine synthase aCBF5 and the ribosomal protein L7Ae. Protein aNOP10 interacts with both aCBF5 and L7Ae. The fourth protein, aGAR1, interacts with aCBF5 and enhances catalytic efficiency. Here, we compared the features of two H/ACA sRNAs, Pab21 and Pab91, from Pyrococcus abyssi. We found that aCBF5 binds much more weakly to Pab91 than to Pab21. Surprisingly, the Pab91 sRNP exhibits a higher catalytic efficiency than the Pab21 sRNP. We thus investigated the molecular basis of the differential efficiencies observed for the assembly and catalytic activity of the two enzymes. For this, we compared profiles of the extent of lead-induced cleavages in these sRNAs during a stepwise reconstitution of the sRNPs, and analyzed the impact of the absence of the aNOP10-L7Ae interaction. Such probing experiments indicated that the sRNAs undergo a series of conformational changes upon RNP assembly. These changes were also evaluated directly by circular dichroism (CD) spectroscopy, a tool highly adapted to analyzing RNA conformational dynamics. In addition, our results reveal that the conformation of helix P1 formed at the base of the H/ACA sRNAs is optimized in Pab21 for efficient aCBF5 binding and RNP assembly. Moreover, P1 swapping improved the assembly of the Pab91 sRNP. Nonetheless, efficient aCBF5 binding probably also relies on the pseudouridylation pocket which is not optimized for high activity in the case of Pab21.

  13. Dynamic conformations of nucleophosmin (NPM1 at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

    Directory of Open Access Journals (Sweden)

    Wei D Duan-Porter

    Full Text Available Nucleophosmin (NPM1 is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM that shared all these properties. We used deuterium exchange mass spectrometry (DXMS to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We tested the importance of interactions at the β-hairpin "latch" by replacing a conserved tyrosine in the middle of the β-hairpin loop with glutamic acid, generating Y67E-NPM. Y67E-NPM did not form stable oligomers and further, prevented wild-type NPM1 oligomerization in a dominant-negative fashion, supporting the critical role of the β-hairpin "latch" in monomer-monomer interactions. Also, we show preferential cleavage by granzyme B at one of two available aspartates (either D161 or D122 in M7-NPM and Y67E-NPM, whereas wild-type NPM1 was cleaved at both sites. Thus, we observed a correlation between the propensity to form oligomers and granzyme B cleavage site selection in nucleophosmin proteins, suggesting that a small change at an important monomer-monomer interface can affect conformational shifts and impact protein-protein interactions.

  14. Dynamic Growth of Pinhole-Free Conformal CH3NH3PbI3 Film for Perovskite Solar Cells.

    Science.gov (United States)

    Li, Bo; Tian, Jianjun; Guo, Lixue; Fei, Chengbin; Shen, Ting; Qu, Xuanhui; Cao, Guozhong

    2016-02-01

    Two-step dipping is one of the popular low temperature solution methods to prepare organic-inorganic halide perovskite (CH3NH3PbI3) films for solar cells. However, pinholes in perovskite films fabricated by the static growth method (SGM) result in low power conversion efficiency (PCE) in the resulting solar cells. In this work, the static dipping process is changed into a dynamic dipping process by controlled stirring PbI2 substrates in CH3NH3I isopropanol solution. The dynamic growth method (DGM) produces more nuclei and decreases the pinholes during the nucleation and growth of perovskite crystals. The compact perovskite films with free pinholes are obtained by DGM, which present that the big perovskite particles with a size of 350 nm are surrounded by small perovskite particles with a size of 50 nm. The surface coverage of the perovskite film is up to nearly 100%. Such high quality perovskite film not only eliminated pinholes, resulting in reduced charge recombination of the solar cells, but also improves the light harvesting efficiency. As a result, the PCE of the perovskite solar cells is increased from 11% for SGM to 13% for DGM.

  15. Wire + Arc Additive Manufacturing

    OpenAIRE

    Williams, Stewart W.; Martina, Filomeno; Addison, Adrian C.; Ding, Jialuo; Pardal, Goncalo; Colegrove, Paul A.

    2016-01-01

    Depositing large components (>10 kg) in titanium, aluminium, steel and other metals is possible using Wire + Arc Additive Manufacturing. This technology adopts arc welding tools and wire as feedstock for additive manufacturing purposes. High deposition rates, low material and equipment costs, and good structural integrity make Wire+Arc Additive Manufacturing a suitable candidate for replacing the current method of manufacturing from solid billets or large forgings, especially with regards to ...

  16. Lanthanide paramagnetic probes for NMR spectroscopic studies of fast molecular conformational dynamics and temperature control. Effective six-site proton exchange in 18-crown-6 by exchange spectroscopy.

    Science.gov (United States)

    Babailov, Sergey P

    2012-02-06

    (1)H and (13)C NMR measurements are reported for the CDCl(3) and CD(2)Cl(2) solutions of [La(18-crown-6)(NO(3))(3)] (I), [Pr(18-crown-6) (NO(3))(3)] (II), [Ce(18-crown-6)(NO(3))(3)] (III), and [Nd(18-crown-6)(NO(3))(3)] (IV) complexes. Temperature dependencies of the (1)H NMR spectra of paramagnetic II-IV have been analyzed using the dynamic NMR (DNMR) methods for six-site exchange. Two types of conformational dynamic processes were identified (the first one is conditioned by interconversion of complex enantiomeric forms and pseudorotation of a macrocycle molecule upon the C(2) symmetry axis; the second one is conditioned by macrocycle molecule inversion). Application of exchange spectroscopy (2D-EXSY) of DNMR for investigation of this dynamic system (II-IV) simplifies the assignment of the NMR signals and represents the first experimental study of multisite exchange. In the present work, the methodology of paramagnetic 4f (Ce, Pr, and Nd) probe applications for the study of free-energy, enthalpy, and entropy changes in chemical exchange processes, as well as the advantages of this method in a comparison with DNMR studies of diamagnetic substances, is discussed. In particular, as a result of paramagnetic chemical shifts in 4f complexes, the range of measurable rate constants expands considerably compared to the analogous range in diamagnetic compounds. Coordination compounds investigated in the paper represent new types of thermometric NMR sensors and lanthanide paramagnetic probes for in situ temperature control in solution.

  17. Welding arc plasma physics

    Science.gov (United States)

    Cain, Bruce L.

    1990-01-01

    The problems of weld quality control and weld process dependability continue to be relevant issues in modern metal welding technology. These become especially important for NASA missions which may require the assembly or repair of larger orbiting platforms using automatic welding techniques. To extend present welding technologies for such applications, NASA/MSFC's Materials and Processes Lab is developing physical models of the arc welding process with the goal of providing both a basis for improved design of weld control systems, and a better understanding of how arc welding variables influence final weld properties. The physics of the plasma arc discharge is reasonably well established in terms of transport processes occurring in the arc column itself, although recourse to sophisticated numerical treatments is normally required to obtain quantitative results. Unfortunately the rigor of these numerical computations often obscures the physics of the underlying model due to its inherent complexity. In contrast, this work has focused on a relatively simple physical model of the arc discharge to describe the gross features observed in welding arcs. Emphasis was placed of deriving analytic expressions for the voltage along the arc axis as a function of known or measurable arc parameters. The model retains the essential physics for a straight polarity, diffusion dominated free burning arc in argon, with major simplifications of collisionless sheaths and simple energy balances at the electrodes.

  18. Study of structural and conformational change in cytochrome, C through molecular dynamic simulation in presence of gold nanoparticles

    Science.gov (United States)

    Moudgil, Lovika; Singh, Baljinder; Kaura, Aman; Singh, Gurinder; Tripathi, S. K.; Saini, G. S. S.

    2017-05-01

    Proteins are the most abundant organic molecules in living system having diverse structures and various functions than the other classes of macromolecules. We have done Molecular Dynamics (MD) simulation of the Cytochrome,C (Cyt,c) protein found in plants, animals and many unicellular animals in the presence of gold nanoparticles (Au NPs). MD results helped to recognize the amino acids that play important role to make the interaction possible between protein and gold surface. In the present study we have examined the structural change of protein in the presence of gold surface and its adsorption on the surface through MD simulations with the help of Gold-Protein (GolP) force field. Results were further analyzed to understand the protein interaction up to molecular level.

  19. Overview of arc design options: Deliverable D2.1

    CERN Document Server

    Chance, Antoine

    2016-01-01

    This document describes the collider layouts to be taken into account for further detailed studies. The optimization of the arc cell lattice and the choice made on the dispersion suppressor are explained. The arc lattice is detailed with the procedures to tune the collider ring and to correct the chromaticity. The correction schemes of the orbit, of the dynamic aperture and of the spurious dispersion are detailed. Finally, the properties of the arc design at the injection energy are shown.

  20. Fluctuation Phenomenon Analysis of an Arc Plasma Spraying Jet

    Institute of Scientific and Technical Information of China (English)

    赵文华; 田阔; 刘笛; 张冠忠

    2001-01-01

    The effects of three factors, including the power supply, the arc behaviour in the arc channel and the fluid dynamic process of the jet, on a plasma spraying jet have been experimentally detected by means of spectroscopic diagnostic techniques. The fast Fourier transform method has been applied to the analysis of the arc voltage and spectral line intensity of the jet. The three factors have been studied and distinguished from each other.

  1. On the arc structures of the Saturnian kilometric radiation

    Science.gov (United States)

    Boudjada, M. Y.; Galopeau, P. H. M.; Rucker, H. O.; Voller, W.

    2012-09-01

    We report on the analysis of the dynamic spectra of the Saturnian kilometric radiation (SKR) recorded by the Cassini Radio and Plasma Wave Science Experiment (RPWS) in the frequency range from 100 kHz to about 1 MHz. We investigate the Saturnian kilometric spectra recorded by RPWS experiment from 01st Jan. 2004 to 31st Dec. 2007. Different Saturnian 'sources' can be defined by spectral characteristics. We show that the SKR presents different kinds of arc structures. Those arcs may be classified in two sets: the 'vertex early arcs' (VEA) and the 'vertex late arcs' (VLA). The arcs of the first group set open toward increasing time, while the arcs of the other one open towards decreasing time. A total of 556 arcs have been observed during the four investigated years, where 310 and 246 correspond, respectively, to the vertex early and late arcs. The arc occurrences are mainly observed when the spacecraft was close to the apoapses, and also when the Cassini latitude was in the range -20° and +20°. Similar VEA and VLA arc structures have been reported in the case of the Jovian hectometric (HOM) and decametric (DAM) radio emissions. In this contribution we put emphasis on the common and unusual arc features by comparing the auroral emissions related to Jupiter and Saturn.

  2. Remarkable conformational flexibility of aqueous 18-crown-6 and its strontium(II) complex-ab initio molecular dynamics simulations.

    Science.gov (United States)

    Canaval, Lorenz R; Hadisaputra, Saprizal; Hofer, Thomas S

    2015-07-07

    Ab initio QMCF-MD simulations of aqueous 18-crown-6 (18C6) and strontium(II)-18-crown-6 (18C6-Sr) were performed to gather insight into their hydration properties. Strongly different characteristics were found for the two solutes in terms of structure and dynamics such as H-bonding. They, however, have in common that their backbone shows high flexibility in aqueous medium, adopting structures significantly differing from idealized gas phase geometries. In particular, planar oxyethylene units stable in the picosecond range occurred in 18C6, while the strontium complex readily exhibits a bent structure. Detailed analysis of this high flexibility was done via two dimensional root mean square deviation plots as well as the evolution of dihedral angles and angles within the simulation trajectory. The vibrational spectra obtained from the QMCF-MD simulations are in excellent agreement with experimental data and show a pronounced blueshift upon complexation of the strontium(II) ion in 18C6.

  3. Resolution of Two Sub-Populations of Conformers and Their Individual Dynamics by Time Resolved Ensemble Level FRET Measurements.

    Directory of Open Access Journals (Sweden)

    Gil Rahamim

    Full Text Available Most active biopolymers are dynamic structures; thus, ensembles of such molecules should be characterized by distributions of intra- or intermolecular distances and their fast fluctuations. A method of choice to determine intramolecular distances is based on Förster resonance energy transfer (FRET measurements. Major advances in such measurements were achieved by single molecule FRET measurements. Here, we show that by global analysis of the decay of the emission of both the donor and the acceptor it is also possible to resolve two sub-populations in a mixture of two ensembles of biopolymers by time resolved FRET (trFRET measurements at the ensemble level. We show that two individual intramolecular distance distributions can be determined and characterized in terms of their individual means, full width at half maximum (FWHM, and two corresponding diffusion coefficients which reflect the rates of fast ns fluctuations within each sub-population. An important advantage of the ensemble level trFRET measurements is the ability to use low molecular weight small-sized probes and to determine nanosecond fluctuations of the distance between the probes. The limits of the possible resolution were first tested by simulation and then by preparation of mixtures of two model peptides. The first labeled polypeptide was a relatively rigid Pro7 and the second polypeptide was a flexible molecule consisting of (Gly-Ser7 repeats. The end to end distance distributions and the diffusion coefficients of each peptide were determined. Global analysis of trFRET measurements of a series of mixtures of polypeptides recovered two end-to-end distance distributions and associated intramolecular diffusion coefficients, which were very close to those determined from each of the pure samples. This study is a proof of concept study demonstrating the power of ensemble level trFRET based methods in resolution of subpopulations in ensembles of flexible macromolecules.

  4. Redox-Dependent Conformational Dynamics of Decameric 2-Cysteine Peroxiredoxin and its Interaction with Cyclophilin 20-3.

    Science.gov (United States)

    Liebthal, Michael; Strüve, Marcel; Li, Xin; Hertle, Yvonne; Maynard, Daniel; Hellweg, Thomas; Viehhauser, Andrea; Dietz, Karl-Josef

    2016-07-01

    2-Cysteine peroxiredoxins (2-CysPrxs) switch between functions as a thiol peroxidase, chaperone, an interaction partner and possibly a proximity-based oxidase in a redox-dependent manner. In photosynthetic eukaryotes, 2-CysPrx localizes to the plastid, functions in the context of photosynthesis and enables an ascorbate peroxidase-independent water-water cycle for detoxifying H2O2 The high degree of evolutionary conservation of 2-CysPrx suggests that the switching is an essential characteristic and needed to transduce redox information to downstream pathways and regulation. The study aimed at exploring the dissociation behavior of 2-CysPrx and its interactions with cyclophilin depending on bulk phase conditions. Isothermal titration microcalorimetry (ITC), dynamic light scattering and size exclusion chromatography (SEC) proved the previously suggested model that reduced 2-CysPrx below a critical transition concentration (CTC) exists in its dimeric state, and above the CTC adopts the decameric state. The presence of cyclophilin 20-3 (Cyp20-3) affected the CTC of a 2-CysPrx decamer suggesting interaction which was further quantified by direct titration of 2-CysPrx with Cyp20-3, and in overlays. Finally catalytic inactivation assays showed the higher catalytic efficiency of 2-CysPrx at pH 8 compared with pH 7.2, but also revealed increased inactivation by hyperoxidation at pH 8. Interestingly, calculation of the average turnover number until inactivation gave rather similar values of 243 and 268 catalytic cycles at pH 8 and pH 7.2, respectively. These quantitative data support a model where 2-CysPrx and Cyp20-3, by interaction, form a redox-sensitive regulatory module in the chloroplast which is under control of the photosynthesis-linked stromal pH value, the redox state and additional stromal protein factor(s).

  5. Solution conformation and dynamics of a tetrasaccharide related to the Lewis{sup X} antigen deduced by NMR relaxation measurements

    Energy Technology Data Exchange (ETDEWEB)

    Poveda, Ana [Universidad Autonoma de Madrid, Servicio Interdepartamental de Investigacion (Spain); Asensio, Juan Luis; Martin-Pastor, Manuel; Jimenez-Barbero, Jesus [Instituto de Quimica Organica, CSIC, Grupo de Carbohidratos (Spain)

    1997-07-15

    {sup 1}H-NMR cross-relaxation rates and nonselective longitudinal relaxation times have been obtained at two magnetic fields (7.0 and 11.8 T) and at a variety of temperatures for the branched tetrasaccharide methyl 3-O-{alpha}-N-acetyl-galactosaminyl-{beta}-galactopyranosyl-(1{sup {yields}}4)[3-O-{alpha}-fucosyl] -glucopyranoside (1), an inhibitor of astrocyte growth. In addition, {sup 13}C-NMR relaxation data have also been recorded at both fields. The {sup 1}H-NMR relaxation data have been interpreted using different motional models to obtain proton-proton correlation times. The results indicate that the GalNAc and Fuc rings display more extensive local motion than the two inner Glc and Gal moieties, since those present significantly shorter local correlation times. The{sup 13}C-NMR relaxation parameters have been interpreted in terms of the Lipari-Szabo model-free approach. Thus, order parameters and internal motion correlation times have been deduced. As obtained for the{sup 1}H-NMR relaxation data, the two outer residues possess smaller order parameters than the two inner rings. Internal correlation times are in the order of 100 ps. The hydroxymethyl groups have also different behaviour,with the exocyclic carbon on the glucopyranoside unit showing the highestS{sup 2}. Molecular dynamics simulations using a solvated system have also been performed and internal motion correlation functions have been deduced from these calculations. Order parameters and interproton distances have been compared to those inferred from the NMR measurements. The obtained results are in fair agreement with the experimental data.

  6. WSTF electrical arc projects

    Science.gov (United States)

    Linley, Larry

    1994-09-01

    The objectives of these projects include the following: validate method used to screen wire insulation with arc tracking characteristics; determine damage resistance to arc as a function of source voltage and insulation thickness; investigate propagation characteristics of Kapton at low voltages; and investigate pyrolytic properties of polyimide insulated (Kapton) wire for low voltage (less than 35 VDC) applications. Supporting diagrams and tables are presented.

  7. Establishment of Transmission Model and Dynamic Contact Analysis for the Double Circular Arc Gear%双圆弧齿轮传动模型的建立与动力学接触分析

    Institute of Scientific and Technical Information of China (English)

    朱琳琳; 武宝林; 李杨

    2015-01-01

    In this paper, the three-dimensional parametric transmission model of double circular arc gear is completed based on the Pro/E software, and the dynamic contact analysis is conducted in the ADAMS software based on multi-body contact dy-namic theory. The output speed, vibration frequency and meshing force of the gear transmission under the given motion and torque are calculated, and the impact of the pressure angle , the whole tooth height h on the contact force are also analyzed. The calculation results reveal the action of actual gears mesh very well. The simulation method and results have an important reference and guidance value to the engineering design and capability checkout for double circular arc gear.%基于Pro/E 软件参数化建立双圆弧齿轮传动模型,基于多体接触动力学理论在ADAMS 软件中进行动力学接触分析,计算了齿轮传动在给定驱动和扭矩下的输出转速、击振频率和动态啮合力,分析法向压力角、全齿高对接触碰撞力的影响。仿真结果和理论分析吻合,对双圆弧齿轮的设计及校核具有参考意义。

  8. Poly(N-isopropylacrylamide) thin films densely grafted onto gold surface: preparation, characterization, and dynamic AFM study of temperature-induced chain conformational changes.

    Science.gov (United States)

    Montagne, Franck; Polesel-Maris, Jérome; Pugin, Raphael; Heinzelmann, Harry

    2009-01-20

    Thermally responsive poly(N-isopropylacrylamide) (PNIPAM) films are attracting considerable attention since they offer the possibility to achieve reversible control over surface wettability and biocompatibility. In this paper, we first report a new and simple method for the grafting under melt of amine-terminated PNIPAM chains onto gold surfaces modified with a self-assembled monolayer (SAM) of reactive thiols. The formation of homogeneous tethered PNIPAM films, whose thickness can be tuned by adjusting polymer molecular weight or SAM reactivity, is evidenced by using the combination of ellipsometry, X-ray photon spectroscopy, infrared spectroscopy (PM-IRRAS), and atomic force microscopy. The calculation of grafting parameters from experimental measurements indicated the synthesis of densely grafted PNIPAM films and allowed us to predict a "brushlike" regime for the chains in good solvent. In a second part, the temperature-induced responsive properties are studied in situ by conducting dynamic AFM measurements using the amplitude modulation technique. Imaging in water environment first revealed the reversible modification of surface morphology below and above the theoretical lower critical solution temperature (LCST) of PNIPAM. Then, the determination of amplitude and phase approach curves at various temperatures provided direct measurement of the evolution of the damping factor, or similarly the dissipated energy, as a function of the probe indentation into the PNIPAM film. Most interestingly, we clearly showed the subtle and progressive thermally induced chain conformational change occurring at the scale of several nanometers around the expected LCST.

  9. Biologically relevant conformational features of linear and cyclic proteolipid protein (PLP) peptide analogues obtained by high-resolution nuclear magnetic resonance and molecular dynamics

    Science.gov (United States)

    Kordopati, Golfo G.; Tzoupis, Haralambos; Troganis, Anastassios N.; Tsivgoulis, Gerasimos M.; Golic Grdadolnik, Simona; Simal, Carmen; Tselios, Theodore V.

    2017-07-01

    Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are destroyed during the progress of multiple sclerosis (MS). The immunodominant PLP139-151 epitope is known to induce experimental autoimmune encephalomyelitis (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell receptor (TCR) during the formation of trimolecular complex with peptide-antigen and major histocompability complex. The conformational behavior of linear and cyclic peptide analogues of PLP, namely PLP139-151 and cyclic (139-151) (L144, R147) PLP139-151, have been studied in solution by means of nuclear magnetic resonance (NMR) methods in combination with unrestrained molecular dynamics simulations. The results indicate that the side chains of mutated amino acids in the cyclic analogue have different spatial orientation compared with the corresponding side chains of the linear analogue, which can lead to reduced affinity to TCR. NMR experiments combined with theoretical calculations pave the way for the design and synthesis of potent restricted peptides of immunodominant PLP139-151 epitope as well as non peptide mimetics that rises as an ultimate goal.

  10. Study of the mechanism of protonated histidine-induced conformational changes in the Zika virus dimeric envelope protein using accelerated molecular dynamic simulations.

    Science.gov (United States)

    Sun, Jixue; Li, Yang; Liu, Pi; Lin, Jianping

    2017-06-01

    The Zika virus has drawn worldwide attention because of the epidemic diseases it causes. It is a flavivirus that has an icosahedral protein shell constituted by an envelope glycoprotein (E-protein) and membrane protein (M-protein) in the mature virion. The multistep process of membrane fusion to infect the host cell is pH-induced. To understand the mechanism of the conformational changes in the (E-M)2 protein homodimer embedded in the membrane, two 200-ns accelerated dynamic simulations were performed under different pH conditions. The low pH condition weakens the interactions and correlations in both E-protein monomers and in the E-M heterodimer. The highly conserved residues, His249, His288, His323 and His446, are protonated under low pH conditions and play key roles in driving the fusion process. The analysis and discussion in this study may provide some insight into the molecular mechanism of Zika virus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Characterization of Sizes of Aggregates of Insulin Analogs and the Conformations of the Constituent Protein Molecules: A Concomitant Dynamic Light Scattering and Raman Spectroscopy Study.

    Science.gov (United States)

    Zhou, Chen; Qi, Wei; Lewis, E Neil; Carpenter, John F

    2016-02-01

    To generate aggregates, 3 insulin analogs, lispro, aspart, and glulisine, were incubated without phenolic preservatives for 30 days at 37 °C. As a function of incubation time, aggregation was quantified with size exclusion chromatography, and the sizes of aggregates and the conformations of the constituent molecules were characterized with concomitant dynamic light scattering and Raman spectroscopy. During incubation, lispro was progressively converted into soluble aggregates with hydrodynamic diameters of circa 15 nm, and 95% of the native protein had aggregated at day 30. Raman spectroscopy documented that aggregation resulted in conversion of a large fraction of native alpha helix into nonnative beta sheet structure and a distortion of disulfide bonds. In contrast, for aspart and glulisine only 20% of the native proteins aggregated after 30 days, and minimal structural perturbations were detected. In addition, consistent with the relative aggregation rates during isothermal incubation, Raman spectroscopy showed that during heating the onset temperature for secondary structural perturbations of lispro occurred 7 °C-10 °C lower than those for aspart or glulisine. Overall the results of this study demonstrated that-as in the case during formation of amyloid fibrils from insulin-formation of soluble aggregates of lispro resulted in a high level of conversion of alpha helix into beta sheet. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Conformational dynamics and the energetics of protein--ligand interactions: role of interdomain loop in human cytochrome P450 reductase.

    Science.gov (United States)

    Grunau, Alex; Geraki, Kalotina; Grossmann, J Günter; Gutierrez, Aldo

    2007-07-17

    highly sensitive to functional structural dynamics involving distal domains. These findings support early theoretical studies which postulate a single protein molecule to be a real, independent thermodynamic ensemble.

  13. History of Neptune's Ring Arcs

    Science.gov (United States)

    Esposito, L. W.; Colwell, J. E.; Canup, R. M.

    1997-07-01

    The recent dynamical calculations for Neptune's Adams ring arcs by Foryta and Sicardy (1996) and Hanninen and Porco (1997) determine the basic evolutionary parameters for this system. The ring evolution is dominated by stochastic events, particularly chaotic motion that causes a migration between the corotation sites (FS96) and collisions near quadrature (HP97). A basic problem is that the high velocity collisions that produce the dusty arcs at the Galatea corotation resonances rapidly depopulate these sites (Colwell and Esposito 1990). With the new results in hand for the evolution of the ring particles over periods of less than a century, we can now calculate the long-term stochastic evolution of the Adams ring. Using a finite Markov chain as a model for this stochastic process, we follow the suggestion by FS96 that corotation sites provide preferential locations for accretion. A more general conclusion is that the longitudinal concentration of material in a few nearby sites (and that the majority of the Adams ring material is residing there) requires either an exceedingly recent event (EC92) or that the corotation sites be absorbing states of the Markov chain.In the latter case, the competing processes of chaotic diffusion and frustrated accretion can provide the arc and clump features as recurrent transient events near the Roche limit. Similar phenomena would be expected for Saturn's F and G rings.

  14. Leaf growth is conformal

    CERN Document Server

    Alim, Karen; Shraiman, Boris I; Boudaoud, Arezki

    2016-01-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  15. Leaf growth is conformal

    Science.gov (United States)

    Alim, Karen; Armon, Shahaf; Shraiman, Boris I.; Boudaoud, Arezki

    2016-10-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  16. Comparing two strategies of dynamic intensity modulated radiation therapy (dIMRT with 3-dimensional conformal radiation therapy (3DCRT in the hypofractionated treatment of high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Yartsev Slav

    2008-01-01

    Full Text Available Abstract Background To compare two strategies of dynamic intensity modulated radiation therapy (dIMRT with 3-dimensional conformal radiation therapy (3DCRT in the setting of hypofractionated high-risk prostate cancer treatment. Methods 3DCRT and dIMRT/Helical Tomotherapy(HT planning with 10 CT datasets was undertaken to deliver 68 Gy in 25 fractions (prostate and simultaneously delivering 45 Gy in 25 fractions (pelvic lymph node targets in a single phase. The paradigms of pelvic vessel targeting (iliac vessels with margin are used to target pelvic nodes and conformal normal tissue avoidance (treated soft tissues of the pelvis while limiting dose to identified pelvic critical structures were assessed compared to 3DCRT controls. Both dIMRT/HT and 3DCRT solutions were compared to each other using repeated measures ANOVA and post-hoc paired t-tests. Results When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p dose, 1–3 Gy over 5/10 dose points; p Conclusion dIMRT/HT nodal and pelvic targeting is superior to 3DCRT in dose delivery and critical structure sparing in the setting of hypofractionation for high-risk prostate cancer. The pelvic targeting paradigm is a potential solution to deliver highly conformal pelvic radiation treatment in the setting of nodal location uncertainty in prostate cancer and other pelvic malignancies.

  17. Dosimetric evaluation of the interplay effect in respiratory-gated RapidArc radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Craig [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213 (United States); Yang, Yong, E-mail: yangy2@upmc.edu; Li, Tianfang; Zhang, Yongqian; Heron, Dwight E.; Huq, M. Saiful [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232 (United States)

    2014-01-15

    Purpose: Volumetric modulated arc therapy (VMAT) with gating capability has had increasing adoption in many clinics in the United States. In this new technique, dose rate, gantry rotation speed, and the leaf motion speed of multileaf collimators (MLCs) are modulated dynamically during gated beam delivery to achieve highly conformal dose coverage of the target and normal tissue sparing. Compared with the traditional gated intensity-modulated radiation therapy technique, this complicated beam delivery technique may result in larger dose errors due to the intrafraction tumor motion. The purpose of this work is to evaluate the dosimetric influence of the interplay effect for the respiration-gated VMAT technique (RapidArc, Varian Medical Systems, Palo Alto, CA). Our work consisted of two parts: (1) Investigate the interplay effect for different target residual errors during gated RapidArc delivery using a one-dimensional moving phantom capable of producing stable sinusoidal movement; (2) Evaluate the dosimetric influence in ten clinical patients’ treatment plans using a moving phantom driven with a patient-specific respiratory curve. Methods: For the first part of this study, four plans were created with a spherical target for varying residual motion of 0.25, 0.5, 0.75, and 1.0 cm. Appropriate gating windows were applied for each. The dosimetric effect was evaluated using EDR2 film by comparing the gated delivery with static delivery. For the second part of the project, ten gated lung stereotactic body radiotherapy cases were selected and reoptimized to be delivered by the gated RapidArc technique. These plans were delivered to a phantom, and again the gated treatments were compared to static deliveries by the same methods. Results: For regular sinusoidal motion, the dose delivered to the target was not substantially affected by the gating windows when evaluated with the gamma statistics, suggesting the interplay effect has a small role in respiratory-gated RapidArc

  18. Conformal transformations and conformal invariance in gravitation

    CERN Document Server

    Dabrowski, Mariusz P; Blaschke, David B

    2008-01-01

    Conformal transformations are frequently used tools in order to study relations between various theories of gravity and Einstein relativity. Because of that, in this paper we discuss the rules of conformal transformations for geometric quantities in general relativity. In particular, we discuss the conformal transformations of the matter energy-momentum tensor. We thoroughly discuss the latter and show the subtlety of the conservation law (i.e., the geometrical Bianchi identity) imposed in one of the conformal frames in reference to the other. The subtlety refers to the fact that conformal transformation ``creates'' an extra matter term composed of the conformal factor which enters the conservation law. In an extreme case of the flat original spacetime the matter is ``created'' due to work done by the conformal transformation to bend the spacetime which was originally flat. We also discuss how to construct the conformally invariant gravity which, in the simplest version, is a special case of the Brans-Dicke t...

  19. Arc Jet Facility Test Condition Predictions Using the ADSI Code

    Science.gov (United States)

    Palmer, Grant; Prabhu, Dinesh; Terrazas-Salinas, Imelda

    2015-01-01

    The Aerothermal Design Space Interpolation (ADSI) tool is used to interpolate databases of previously computed computational fluid dynamic solutions for test articles in a NASA Ames arc jet facility. The arc jet databases are generated using an Navier-Stokes flow solver using previously determined best practices. The arc jet mass flow rates and arc currents used to discretize the database are chosen to span the operating conditions possible in the arc jet, and are based on previous arc jet experimental conditions where possible. The ADSI code is a database interpolation, manipulation, and examination tool that can be used to estimate the stagnation point pressure and heating rate for user-specified values of arc jet mass flow rate and arc current. The interpolation is performed in the other direction (predicting mass flow and current to achieve a desired stagnation point pressure and heating rate). ADSI is also used to generate 2-D response surfaces of stagnation point pressure and heating rate as a function of mass flow rate and arc current (or vice versa). Arc jet test data is used to assess the predictive capability of the ADSI code.

  20. Circular-Arc Cartograms

    CERN Document Server

    Kämper, Jan-Hinrich; Nöllenburg, Martin

    2011-01-01

    We present a new circular-arc cartogram model in which countries are drawn with circular arcs instead of straight-line segments. Given a geographic map and values associated with each country in the map, the cartogram is a new map in which the areas of the countries represent the corresponding values. In the circular-arc cartogram model straight-line segments can be replaced with circular arcs in order to achieve the desired areas, while the corners of the polygons defining each country remain fixed. The countries in circular-arc cartograms have the aesthetically pleasing appearance of clouds or snowflakes, depending on whether their edges are bent outwards or inwards. This makes is easy to determine whether a country has grown or shrunk, just by its overall shape. We show that determining whether a given map and area-values can be realized with a circular-arc cartogram is an NP-hard problem. Next we describe a heuristic method for constructing circular-arc cartograms, which uses a max-flow computation on the...

  1. Conformal mechanics

    CERN Document Server

    Gonera, Joanna

    2012-01-01

    The SL(2,R) invariant Hamiltonian systems are discussed within the frame- work of the orbit method. It is shown that both dynamics and symmetry trans- formations are globally well-defined on phase space. The flexibility in the choice of time variable and Hamiltonian function described in the paper by de Alfaro et al. (Nuovo Cim. 34A (1976),569) is related to the nontrivial global structure of 1 + 0-dimensional space-time. The operational definition of time is discussed.

  2. Trajectory Modulated Arc Therapy: A Fully Dynamic Delivery With Synchronized Couch and Gantry Motion Significantly Improves Dosimetric Indices Correlated With Poor Cosmesis in Accelerated Partial Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Jieming; Atwood, Todd; Eyben, Rie von; Fahimian, Benjamin; Chin, Erika; Horst, Kathleen [Department of Radiation Oncology, Stanford University, California (United States); Otto, Karl [Department of Physics, University of British Columbia, British Columbia (Canada); Hristov, Dimitre, E-mail: dimitre.hristov@stanford.edu [Department of Radiation Oncology, Stanford University, California (United States)

    2015-08-01

    Purpose: To develop planning and delivery capabilities for linear accelerator–based nonisocentric trajectory modulated arc therapy (TMAT) and to evaluate the benefit of TMAT for accelerated partial breast irradiation (APBI) with the patient in prone position. Methods and Materials: An optimization algorithm for volumetrically modulated arc therapy (VMAT) was generalized to allow for user-defined nonisocentric TMAT trajectories combining couch rotations and translations. After optimization, XML scripts were automatically generated to program and subsequently deliver the TMAT plans. For 10 breast patients in the prone position, TMAT and 6-field noncoplanar intensity modulated radiation therapy (IMRT) plans were generated under equivalent objectives and constraints. These plans were compared with regard to whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose. Results: For TMAT APBI, nonisocentric collision-free horizontal arcs with large angular span (251.5 ± 7.9°) were optimized and delivered with delivery time of ∼4.5 minutes. Percentage changes of whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose for TMAT relative to IMRT were −10.81% ± 6.91%, −27.81% ± 7.39%, −14.82% ± 9.67%, and 39.40% ± 10.53% (P≤.01). Conclusions: This is a first demonstration of end-to-end planning and delivery implementation of a fully dynamic APBI TMAT. Compared with IMRT, TMAT resulted in marked reduction of the breast tissue volume irradiated at high doses.

  3. Conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in conformal space

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The conformal geometry of regular hypersurfaces in the conformal space is studied.We classify all the conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in the conformal space up to conformal equivalence.

  4. Commissioning and first clinical application of mARC treatment

    Energy Technology Data Exchange (ETDEWEB)

    Dzierma, Yvonne; Nuesken, Frank G.; Kremp, Stephanie; Palm, Jan; Licht, Norbert P.; Ruebe, Christian [Universitaetsklinikum des Saarlandes, Klinik fuer Strahlentherapie und Radioonkologie, Homburg, Saarland (Germany)

    2014-11-15

    The modulated arc (mARC) technique has recently been introduced for Siemens ARTISTE linear accelerators. We present the first experiences with the commissioning of the system and first patient treatments. Treatment planning and delivery are presented for the Prowess Panther treatment planning system or, alternatively, an in-house code. Dosimetric verification is performed both by point dose measurements and in 3D dose distribution. Depending on the target volume, one or two arcs can be used to create highly conformal plans. Dosimetric verification of the converted mARC plans with step-and-shoot plans shows deviations below 1 % in absolute point dose; in the 3D dose distribution, over 95 % of the points pass the 3D gamma criteria (3 % deviation in local dose and 3 mm distance to agreement for doses > 20 % of the maximum). Patient specific verification of the mARC dose distribution with the calculations has a similar pass rate. Treatment times range between 2 and 5 min for a single arc. To our knowledge, this is the first report of clinical application of the mARC technique. The mARC offers the possibility to save significant amounts of time, with single-arc treatments of only a few minutes achieving comparable dose distribution to IMRT plans taking up to twice as long. (orig.) [German] Die mARC (modulated arc) Technik wurde vor kurzen fuer Siemens ARTISTE Linearbeschleuniger eingefuehrt. Wir zeigen die ersten Erfahrungen mit der Kommissionierung des Systems sowie die ersten Patientenbestrahlungen. Bestrahlungsplanung und Behandlung werden fuer das Prowess Panther Bestrahlungsplanungssystem oder alternativ in einer in-house-Loesung praesentiert. Die dosimetrische Verifikation wurde sowohl mit Punktmessungen als auch fuer die 3D-Dosisverteilung durchgefuehrt. Je nach Zielvolumen koennen mit einem oder zwei Boegen hochkonformale Plaene erzeugt werden. Die dosimetrische Verifikation konvertierter mARC-Plaene gegen step-and-shoot-Plaene weicht in absoluter Dosis um

  5. Pulsed plasma arc cladding

    Institute of Scientific and Technical Information of China (English)

    龙; 白钢; 李振民; 张赋升; 杨思乾

    2004-01-01

    A prototype of Pulsed Plasma Arc Cladding system was developed, in which single power source supplies both transferred plasma arc (TPA) and non-transferred plasma arc (N-TPA). Both plasmas work in turn in a high frequency controlled by an IGBT connecting nozzle and workpiece. The working frequency of IGBT ranges from 50 ~ 7000Hz, in which the plasmas can work in turn smoothly. Higher than 500 Hz of working frequency is suggested for promotion of cladding quality and protection of IGBT. Drag phenomenon of TPA intensifies as the frequency goes up, which tends to increase the current proportion of TPA and suppress N-TPA. The occupation ratio of IGBT can be regulated from 5% ~ 95%, which balances the power supplies of both plasmas. An occupation ratio higher than 50% gives adequate proportion of arc current for N-TPA to preheat powder.

  6. Filtered cathodic arc source

    Science.gov (United States)

    Falabella, Steven; Sanders, David M.

    1994-01-01

    A continuous, cathodic arc ion source coupled to a macro-particle filter capable of separation or elimination of macro-particles from the ion flux produced by cathodic arc discharge. The ion source employs an axial magnetic field on a cathode (target) having tapered sides to confine the arc, thereby providing high target material utilization. A bent magnetic field is used to guide the metal ions from the target to the part to be coated. The macro-particle filter consists of two straight solenoids, end to end, but placed at 45.degree. to one another, which prevents line-of-sight from the arc spot on the target to the parts to be coated, yet provides a path for ions and electrons to flow, and includes a series of baffles for trapping the macro-particles.

  7. Cálculo independente de dose para tratamentos de arco dinâmico com colimador micromultilâminas Independent dose calculation for dynamic arc treatments delivered with micromultileaf collimator

    Directory of Open Access Journals (Sweden)

    Juan Fernando Delgado

    2006-10-01

    colimador micromultilâminas, nos quais um cálculo manual é muito difícil ou inviável, pela complexidade da técnica.OBJECTIVE: In treatment techniques such as dynamic arc, the manual verification of treatment planning system calculations is very difficult. In these cases, the use of computational tools is useful and becomes an essential component of the quality assurance program. MATERIALS AND METHODS: A worksheet-based software has been created to perform an independent dose or monitor unit calculation in treatments applying the dynamic arc technique delivered with micromultileaf collimator. The dose values calculated per arc and per complete treatment, are compared with values obtained from BrainScan v5.3 treatment planning system. The software has been tested with 229 dynamic arc fields representing 42 skull treatments. From these 229 fields, 109 have been calculated in 3D reconstruction of patients CT images, 109 in reconstruction of polymethylmetacrylate phantom images, and 21 in reconstruction of images from a water equivalent phantom. RESULTS: The mean difference of total doses found in the 42 treatments (composites of one or more dynamic arcs, between the verification software and the treatment planning system, was of +1.73% with a 0.76% standard deviation. The maximum difference was 3.32% and the minimum -0.20%. When the 229 dynamic arcs were tested one by one, the average difference found was 1.61% with a 1.04% standard deviation. Maximum and minimum differences were, respectively 4.01% and -2.04%. As a result of the test, in 80.35% the doses calculated have presented a ± 2.5% difference in relation to the doses generated by the planning system. CONCLUSION: The software presented in this study is recommended for checking point dose included in treatment plans as an integral part of the process of quality assurance in radiotherapy and stereotactic radiosurgery when the dynamic arc technique is utilized in treatment with micromultileaf collimator, where a

  8. Clinical utility of RapidArcTM radiotherapy technology

    Directory of Open Access Journals (Sweden)

    Infusino E

    2015-11-01

    Full Text Available Erminia Infusino Department of Radiotherapy, Campus Bio-Medico University Hospital, Rome, Italy Abstract: RapidArcTM is a radiation technique that delivers highly conformal dose distributions through the complete rotation (360° and speed variation of the linear accelerator gantry. This technique, called volumetric modulated arc therapy (VMAT, compared with conventional radiotherapy techniques, can achieve high-target volume coverage and sparing damage to normal tissues. RapidArc delivers precise dose distribution and conformity similar to or greater than intensity-modulated radiation therapy in a short time, generally a few minutes, to which image-guided radiation therapy is added. RapidArc has become a currently used technology in many centers, which use RapidArc technology to treat a large number of patients. Large and small hospitals use it to treat the most challenging cases, but more and more frequently for the most common cancers. The clinical use of RapidArc and VMAT technology is constantly growing. At present, a limited number of clinical data are published, mostly concerning planning and feasibility studies. Clinical outcome data are increasing for a few tumor sites, even if only a little. The purpose of this work is to discuss the current status of VMAT techniques in clinical use through a review of the published data of planning systems and clinical outcomes in several tumor sites. The study consisted of a systematic review based on analysis of manuscripts retrieved from the PubMed, BioMed Central, and Scopus databases by searching for the keywords "RapidArc", "Volumetric modulated arc radiotherapy", and "Intensity-modulated radiotherapy". Keywords: IMRT, VMAT, SBRT, SRS, treatment planning software 

  9. Using arc voltage to locate the anode attachment in plasma arc cutting

    Science.gov (United States)

    Osterhouse, D. J.; Lindsay, J. W.; Heberlein, J. V. R.

    2013-06-01

    Plasma arc cutting is a widely used industrial process in which an electric arc in the form of a high velocity plasma jet is used to melt and blow away metal. The arc attaches inside the resulting cut slot, or kerf, where it both provides a large heat flux and determines the flow dynamics of the plasma. Knowledge of the position of the arc attachment is essential for understanding the phenomena present at the work piece. This work presents a new method of measuring the location of the arc attachment in which the arc voltage is measured during the cutting of a range of work piece thicknesses. The attachment location is then interpreted from the voltages. To support the validity of this method, the kerf shape, dross particle size and dross adhesion to the work piece are also observed. While these do not conclusively give an attachment location, they show patterns which are consistent with the attachment location found from the voltage measurements. The method is demonstrated on the cutting of mild steel, where the arc attachment is found to be stationary in the upper portion of the cut slot and in reasonable agreement with existing published findings. For a process optimized for the cutting of 12.7 mm mild steel, the attachment is found at a depth of 1.5-3.4 mm. For a slower process optimized for the cutting of 25.4 mm mild steel, the attachment is found at a depth of 3.4-4.8 mm, which enhances heat transfer further down in the kerf, allowing cutting of the thicker work piece. The use of arc voltage to locate the position of the arc attachment is unique when compared with existing methods because it is entirely independent of the heat distribution and visualization techniques.

  10. Radiotherapy for large cutaneous angiosarcoma of face with RapidArc (VMAT

    Directory of Open Access Journals (Sweden)

    Mirza Athar Ali

    2015-01-01

    Full Text Available Angiosarcoma is a rare malignancy of vascular origin. It can affect any part of the body, head and neck region being probably the most common site of diagnosis. We present here a case of Angiosarcoma of face in a 67-year-old elderly gentleman who was treated with RapidArc – volumetric modulated arc therapy (VMAT for recurrence after surgery, radiotherapy and chemotherapy. As an alternative to Electron Beam Therapy, RapidArc with skin bolus can be considered for large complex shaped targets with irregular surface and tissue inhomogeneity. RapidArc plan can achieve adequate target coverage with acceptable dose homogeneity and conformity.

  11. DMLC motion tracking of moving targets for intensity modulated arc therapy treatment - a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Zimmerman, Jens; Korreman, Stine; Persson, Gitte (Dept. of Radiation Oncology, Rigshospitalet, Univ. of Copenhagen, Copenhagen (Denmark)); Cattell, Herb; Svatos, Michelle (Varian Medical Systems, Palo Alto, CA (United States)); Sawant, Amit; Venkat, Raghu; Carlson, David; Keall, Paul (Stanford Univ., Stanford, CA (United States))

    2009-02-15

    Intensity modulated arc therapy offers great advantages with the capability of delivering a fast and highly conformal treatment. However, moving targets represent a major challenge. By monitoring a moving target it is possible to make the beam follow the motion, shaped by a Dynamic MLC (DMLC). The aim of this work was to evaluate the dose delivered to moving targets using the RapidArcTM (Varian Medical Systems, Inc.) technology with and without a DMLC tracking algorithm. Material and methods. A Varian Clinac iX was equipped with a preclinical RapidArcTM and a 3D DMLC tracking application. A motion platform was placed on the couch, with the detectors on top: a PTW seven29 and a Scandidos Delta4. One lung plan and one prostate plan were delivered. Motion was monitored using a Real-time Position Management (RPM) system. Reference measurements were performed for both plans with both detectors at state (0) 'static, no tracking'. Comparing measurements were made at state (1) 'motion, no tracking' and state (2) 'motion, tracking'. Results. Gamma analysis showed a significant improvement from measurements of state (1) to measurements of state (2) compared to the state (0) measurements: Lung plan; from 87 to 97% pass. Prostate plan; from 81 to 88% pass. Sub-beam information gave a much reduced pattern of periodically spatial deviating dose points for state (2) than for state (1). Iso-dose curve comparisons showed a slightly better agreement between state (0) and state (2) than between state (0) and state (1). Conclusions. DMLC tracking together with RapidArcTM make a feasible combination and is capable of improving the dose distribution delivered to a moving target. It seems to be of importance to minimize noise influencing the tracking, to gain the full benefit from the application.

  12. Volumetric Modulated Arc Therapy, Conventional Intensity-modulated Radiotherapy and Three-Dimensional Conformal Techniques for Upper Thoracic Esophageal Cancer: A Planning Comparison Study%胸上段食管癌容积旋转调强和静态调强与三维适形放疗计划的剂量学比较

    Institute of Scientific and Technical Information of China (English)

    张瑞; 习勉; 李巧巧; 赵磊; 黄晓波; 何立儒; 胡永红; 刘孟忠

    2012-01-01

    [目的]比较容积旋转调强( VMAT)、静态调强(sIMRT)与三维适形放疗(3DCRT)技术在胸上段食管癌的剂量学差异.[方法]选取7例局部晚期胸上段食管癌患者,分别制定3DCRT、7野sIMRT和360度单弧VMAT 3套放疗计划,处方剂量统一为60 Gy/30F.比较靶区、危及器官的剂量体积参数,加速器的总机器跳数(MU)和有效治疗时间(TT)等.[结果]VMAT与IMRT的靶区剂量分布基本一致,均优于3DCRT.对于正常组织,三组计划中肺、心脏的受照剂量均无明显差异,但IMRT与VMAT可较3DCRT更好的保护脊髓.3DCRT、IMRT、VMAT的MU分别为537±92、601±122、682±139,有效治疗时间(min)分别为3.9±0.3、6.0±0.7、4.7±0.7 (P< 0.05).[结论]与3DCRT相比,VMAT与IMRT在胸上段食管癌均有一定的剂量学优势,但VMAT较IMRT可显著提高治疗效率.%[Objective] A planning study was performed to compare volumetric modulated arc therapy (VMAT), static intensity-modulated radiotherapy (sIMRT), and three-dimensional conformal radiotherapy (3DCRT) for upper thoracic esophageal cancer. [Methods] Seven patients with loco-regionally advanced upper thoracic esophageal cancer were included. Based on the identical CT and planning target volume (PTV), three plans (3DCRT, sIMRT with seven fields, VMAT with a single arc) were generated. Dose prescription was set to 60Gy in 30 fractions. Dose volume histograms, MU and delivery time were evaluated to assess plan quality. [Results] In comparison to 3DCRT, both VMAT and IMRT provided a systematic improvement in PTV coverage. For normal tissues, equivalent sparing of lung and heart were achieved with three plans. However, IMRT and VMAT showed a superior sparing compared with 3DCRT for spinal cord. The MU/fraction was as follows; 537 ± 92 for 3DCRT, 601 ± 122 for IMRT, and 682 ± 139 for VMAT. Effective treatment time for 3DCRT, IMRT and VMAT were (3.9 ± 0.3) min, (6.0 ± 0.7) min and (4.7 ± 0.7)min, respectively (P< 0

  13. Synthesis, characterisation, conformational preferences, dynamic NMR studies and antimicrobial evaluation of N-nitroso- and N-formyl-c-3,t-3-dimethyl-r-2,c-7-diphenyl-1,4-diazepan-5-ones

    Science.gov (United States)

    Ponnuswamy, S.; Akila, A.; Kiruthiga devi, D.; Maheshwaran, V.; Ponnuswamy, M. N.

    2016-04-01

    The stereochemical preferences of N-nitroso- and N-formyl-c-3,t-3-dimethyl-r-2,c-7-diphenyl-1,4-diazepan-5-ones 3 & 4, respectively, have been determined using 1D and 2D NMR spectral techniques. Interestingly, the N-nitroso compound 3 is found to prefer an equilibrium between alternate chair conformations with diaxial phenyl groups, while the N-formyl compound 4 prefers flattened boat conformation. This is stereochemically a novel report on the flexible rings adopting a chair conformation with diaxial phenyl groups. The X-ray crystal structure of N-nitroso-c-3,t-3-dimethyl-r-2,c-7-diphenyl-1,4-diazepan-5-one (3) also supports the chair conformation with diaxial phenyl groups. Dynamic 1H NMR spectral studies have been carried out on the N-nitroso and N-formyl diazepan-5-ones 3 &4 and the energy barriers for N-NO and N-CO rotations are found to be 88.7 and 75.7 kJ/mol, respectively. The antimicrobial activities have been determined for the compounds 2-4 and it is found that all the compounds exhibit significant antibacterial and antifungal activities when compared to the standard chloramphenicol.

  14. Conformable eddy current array delivery

    Science.gov (United States)

    Summan, Rahul; Pierce, Gareth; Macleod, Charles; Mineo, Carmelo; Riise, Jonathan; Morozov, Maxim; Dobie, Gordon; Bolton, Gary; Raude, Angélique; Dalpé, Colombe; Braumann, Johannes

    2016-02-01

    The external surface of stainless steel containers used for the interim storage of nuclear material may be subject to Atmospherically Induced Stress Corrosion Cracking (AISCC). The inspection of such containers poses a significant challenge due to the large quantities involved; therefore, automating the inspection process is of considerable interest. This paper reports upon a proof-of-concept project concerning the automated NDT of a set of test containers containing artificially generated AISCCs. An Eddy current array probe with a conformable padded surface from Eddyfi was used as the NDT sensor and end effector on a KUKA KR5 arc HW robot. A kinematically valid cylindrical raster scan path was designed using the KUKA|PRC path planning software. Custom software was then written to interface measurement acquisition from the Eddyfi hardware with the motion control of the robot. Preliminary results and analysis are presented from scanning two canisters.

  15. Modeling of Arc Force in Plasma Arc Welding

    Institute of Scientific and Technical Information of China (English)

    GAO Zhonglin; HU Shengsun; YIN Fengliang; WANG Rui

    2008-01-01

    A three. dimensional mathematical model for the transferred-type argon arc was developed to describe arc force on the anode surface. The software ANSYS was employed to solve the model. The model includes a part of torch and tungsten electrode to achieve m ore reasonable results. The arc temperature and flow fields were derived. And the influences of welding parameters on arc force were also studied. The simulated results show that arc pressure at the anode are dependent on the welding current, plasma gas flow rate and electrode neck-in, while not sensitive to arc length.

  16. Non-conformable, partial and conformable transposition

    DEFF Research Database (Denmark)

    König, Thomas; Mäder, Lars Kai

    2013-01-01

    Although member states are obliged to transpose directives into domestic law in a conformable manner and receive considerable time for their transposition activities, we identify three levels of transposition outcomes for EU directives: conformable, partially conformable and non-conformable....... Compared with existing transposition models, which do not distinguish between different transposition outcomes, we examine the factors influencing each transposition process by means of a competing risk analysis. We find that preference-related factors, in particular the disagreement of a member state...... and the Commission regarding a directive’s outcome, play a much more strategic role than has to date acknowledged in the transposition literature. Whereas disagreement of a member state delays conformable transposition, it speeds up non-conformable transposition. Disagreement of the Commission only prolongs...

  17. Conformal frames in cosmology

    CERN Document Server

    Domènech, Guillem

    2016-01-01

    From higher dimensional theories, e.g. string theory, one expects the presence of non-minimally coupled scalar fields. We review the notion of conformal frames in cosmology and emphasize their physical equivalence, which holds at least at a classical level. Furthermore, if there is a field, or fields, which dominates the universe, as it is often the case in cosmology, we can use such notion of frames to treat our system, matter and gravity, as two different sectors. On one hand, the gravity sector which describes the dynamics of the geometry and on the other hand the matter sector which has such geometry as a playground. We use this interpretation to build a model where the fact that a curvaton couples to a particular frame metric could leave an imprint in the CMB.

  18. Conformational Analysis of Indole Alkaloids Corynantheine and Dihydrocorynantheine by Dynamic 1H NMR Spectroscopy and Computational Methods: Steric Effects of Ethyl vs Vinyl Group

    DEFF Research Database (Denmark)

    Stærk, Dan; Norrby, Per-Ola; Jaroszewski, Jerzy W.

    2001-01-01

    . Line-shape analysis yielded enthalpy of activation DeltaH(double dagger) = 71 +/- 6 kJ/mol, and entropy of activation DeltaS(double dagger) = 33 +/- 6 J/mol(.)K. The major and minor conformation contains the methyl ether group above and below the plane of the ring, respectively, as determined by low...... bulk of the vinyl and the ethyl group. The conformational equilibria involving the side chain rotation as well as inversion of the bridgehead nitrogen in corynantheine and dihydrocorynantheine was studied by force-field (Amber(*) and MMFF) and ab initio (density-functional theory at the B3LYP/6-31G...

  19. Theory of Parabolic Arcs in Interstellar Scintillation Spectra

    CERN Document Server

    Cordes, J M; Stinebring, D R; Coles, W A; Cordes, James M.; Rickett, Barney J.; Stinebring, Daniel R.; Coles, William A.

    2004-01-01

    Our theory relates the secondary spectrum, the 2D power spectrum of the radio dynamic spectrum, to the scattered pulsar image in a thin scattering screen geometry. Recently discovered parabolic arcs in secondary spectra are generic features for media that scatter radiation at angles much larger than the rms scattering angle. Each point in the secondary spectrum maps particular values of differential arrival-time delay and fringe rate (or differential Doppler frequency) between pairs of components in the scattered image. Arcs correspond to a parabolic relation between these quantities through their common dependence on the angle of arrival of scattered components. Arcs appear even without consideration of the dispersive nature of the plasma. Arcs are more prominent in media with negligible inner scale and with shallow wavenumber spectra, such as the Kolmogorov spectrum, and when the scattered image is elongated along the velocity direction. The arc phenomenon can be used, therefore, to constrain the inner scal...

  20. Effect of Energetic Electrons on Quiet Auroral Arc Formation

    Science.gov (United States)

    Hasegawa, Hiroki; Ohno, Nobuaki; Sato, Tetsuya

    2010-11-01

    The theory of feedback instability between the magnetosphere and ionosphere is believed as one of the candidate to explain the formation of quiet auroral arc. Then, some magneto-hydro- dynamics simulations showed the arc formation by this macroscopic instability, while the effect of auroral energetic electrons on the arc formation was neglected or given as a macroscopic parameter in these simulations. On the other hand, because of the recent development of particle simulations, auroral energetic electrons are thought to be produced by the super ion-acoustic double layer that should be created by microscopic instability. To make close investigation of auroral arc formation, it is necessary to consider the interaction with microscopic instability. In this paper, we numerically study the effect of energetic electrons on quiet auroral arc formation by means of the Macro-Micro Interlocked simulation.

  1. Arc Heated Scramjet Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Arc Heated Scramjet Test Facility is an arc heated facility which simulates the true enthalpy of flight over the Mach number range of about 4.7 to 8 for free-jet...

  2. ARc Welding (Industrial Processing Series).

    Science.gov (United States)

    ARC WELDING , *BIBLIOGRAPHIES), (*ARC WELDS, BIBLIOGRAPHIES), ALUMINUM ALLOYS, TITANIUM ALLOYS, CHROMIUM ALLOYS, METAL PLATES, SPOT WELDING , STEEL...INERT GAS WELDING , MARAGING STEELS, MICROSTRUCTURE, HEAT RESISTANT ALLOYS, HEAT RESISTANT METALS, WELDABILITY, MECHANICAL PROPERTIES, MOLYBDENUM ALLOYS, NICKEL ALLOYS, RESISTANCE WELDING

  3. Interconverting conformations of variants of the human amyloidogenic protein beta2-microglobulin quantitatively characterized by dynamic capillary electrophoresis and computer simulation

    DEFF Research Database (Denmark)

    Heegaard, Niels H H; Jørgensen, Thomas J D; Cheng, Lei

    2006-01-01

    Capillary electrophoretic separation profiles of cleaved variants of beta2-microglobulin (beta2m) reflect the conformational equilibria existing in solutions of these proteins. The characterization of these equilibria is of interest since beta2m is responsible for amyloid formation in dialysis-re...

  4. SU-E-J-70: Feasibility Study of Dynamic Arc and IMRT Treatment Plans Utilizing Vero Treatment Unit and IPlan Planning Computer for SRS/FSRT Brain Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Huh, S; Lee, S; Dagan, R; Malyapa, R; Mendenhall, N; Mendenhall, W; Ho, M; Hough, D; Yam, M; Li, Z [UFPTI, Jacksonville, FL (United States)

    2014-06-01

    Purpose: To investigate the feasibility of utilizing Dynamic Arc (DA) and IMRT with 5mm MLC leaf of VERO treatment unit for SRS/FSRT brain cancer patients with non-invasive stereotactic treatments. The DA and IMRT plans using the VERO unit (BrainLab Inc, USA) are compared with cone-based planning and proton plans to evaluate their dosimetric advantages. Methods: The Vero treatment has unique features like no rotational or translational movements of the table during treatments, Dynamic Arc/IMRT, tracking of IR markers, limitation of Ring rotation. Accuracies of the image fusions using CBCT, orthogonal x-rays, and CT are evaluated less than ∼ 0.7mm with a custom-made target phantom with 18 hidden targets. 1mm margin is given to GTV to determine PTV for planning constraints considering all the uncertainties of planning computer and mechanical uncertainties of the treatment unit. Also, double-scattering proton plans with 6F to 9F beams and typical clinical parameters, multiple isocenter plans with 6 to 21 isocenters, and DA/IMRT plans are evaluated to investigate the dosimetric advantages of the DA/IMRT for complex shape of targets. Results: 3 Groups of the patients are divided: (1) Group A (complex target shape), CI's are same for IMRT, and DGI of the proton plan are better by 9.5% than that of the IMRT, (2) Group B, CI of the DA plans (1.91+/−0.4) are better than cone-based plan, while DGI of the DA plan is 4.60+/−1.1 is better than cone-based plan (5.32+/−1.4), (3) Group C (small spherical targets), CI of the DA and cone-based plans are almost the same. Conclusion: For small spherical targets, cone-based plans are superior to other 2 plans: DS proton and DA plans. For complex or irregular plans, dynamic and IMRT plans are comparable to cone-based and proton plans for complex targets.

  5. Variable polarity arc welding

    Science.gov (United States)

    Bayless, E. O., Jr.

    1991-01-01

    Technological advances generate within themselves dissatisfactions that lead to further advances in a process. A series of advances in welding technology which culminated in the Variable Polarity Plasma Arc (VPPA) Welding Process and an advance instituted to overcome the latest dissatisfactions with the process: automated VPPA welding are described briefly.

  6. Thermal Arc Spray Overview

    Science.gov (United States)

    Hafiz Abd Malek, Muhamad; Hayati Saad, Nor; Kiyai Abas, Sunhaji; Mohd Shah, Noriyati

    2013-06-01

    Usage of protective coating for corrosion protection was on highly demand during the past decade; and thermal spray coating played a major part during that time. In recent years, the thermal arc spray coating becomes a popular coating. Many big players in oil and gas such as PETRONAS, EXXON MOBIL and SHELL in Malaysia tend to use the coating on steel structure as a corrosion protection. Further developments in coating processes, the devices, and raw materials have led to expansion of functional coatings and applications scope from conventional coating to specialized industries. It is widely used because of its ability to withstand high process temperature, offer advantages in efficiency, lower cost and acts as a corrosion protection. Previous research also indicated that the thermal arc spray offers better coating properties compared to other methods of spray. This paper reviews some critical area of thermal spray coating by discussing the process/parameter of thermal arc spray technology and quality control of coating. Coating performance against corrosion, wear and special characteristic of coating are also described. The field application of arc spray technology are demonstrated and reviewed.

  7. ALICE: ARC integration

    CERN Document Server

    Anderlik, C; Kleist, J; Peters, A; Saiz, P

    2008-01-01

    AliEn or Alice Environment is the Grid middleware developed and used within the ALICE collaboration for storing and processing data in a distributed manner. ARC (Advanced Resource Connector) is the Grid middleware deployed across the Nordic countries and gluing together the resources within the Nordic Data Grid Facility (NDGF). In this paper we will present our approach to integrate AliEn and ARC, in the sense that ALICE data management and job processing can be carried out on the NDGF infrastructure, using the client tools available in AliEn. The inter-operation has two aspects, one is the data management part and the second the job management aspect. The first aspect was solved by using dCache across NDGF to handle data. Therefore, we will concentrate on the second part. Solving it, was somewhat cumbersome, mainly due to the different computing models employed by AliEn and ARC. AliEN uses an Agent based pull model while ARC handles jobs through the more 'traditional' push model. The solution comes as a modu...

  8. ALICE-ARC integration

    DEFF Research Database (Denmark)

    Anderlik, Csaba; Gregersen, Anders Rhod; Kleist, Josva;

    2008-01-01

    Data Grid Facility (NDGF). In this paper we will present our approach to integrate AliEn and ARC, in the sense that ALICE data management and job processing can be carried out on the NDGF infrastructure, using the client tools available in AliEn. The interoperation has two aspects, one is the data...

  9. Gas tungsten arc welder

    Science.gov (United States)

    Christiansen, D.W.; Brown, W.F.

    A welder for automated closure of fuel pins by a gas tungsten arc process in which a rotating length of cladding is positioned adjacent a welding electrode in a sealed enclosure. An independently movable axial grinder is provided in the enclosure for refurbishing the used electrode between welds.

  10. Research on Accurate Modeling and Dynamic Contact Analysis of Double Circular Arc Gear%双圆弧齿轮的精确建模与动态接触分析

    Institute of Scientific and Technical Information of China (English)

    徐文博; 刘世军; 李志胜; 黄红涛

    2013-01-01

    基于SolidWorks操作平台介绍了双圆弧齿轮的三维精确建模的方法,并可以使用VBA语言对其端面齿廓参数化,建立的三维模型导入到Ansys/LS-DYNA中,运用其显式非线性动力分析程序,对其进行动态接触分析,对双圆弧齿轮的设计计算具有一定的参考意义.%Based on SolidWorks operation platform, the accurate 3d modeling method due to the complexity of the double circular arc gear is introduced. Using VBA language, the gear surface is parametered. Then a 3d model is established and imported into the Ansys/ls - dyna. And using its explicit nonlinear dynamic analysis program, the dynamic contact analysis carried out, it has the certain reference significance to design and calculation.

  11. Computer simulation to arc spraying

    Institute of Scientific and Technical Information of China (English)

    梁志芳; 李午申; 王迎娜

    2004-01-01

    The arc spraying process is divided into two stages: the first stage is atomization-spraying stream (ASS) and the second one is spraying deposition (SD). Then study status is described of both stages' physical model and corresponding controlling-equation. Based on the analysis of study status, the conclusion as follows is got. The heat and mass transfer models with two or three dimensions in ASS stage should be established to far deeply analyses the dynamical and thermal behavior of the overheat droplet. The statistics law of overheated droplets should be further studied by connecting simulation with experiments. More proper validation experiments should be designed for flattening simulation to modify the models in SD stage.

  12. Viscous conformal gauge theories

    DEFF Research Database (Denmark)

    Toniato, Arianna; Sannino, Francesco; Rischke, Dirk H.

    2017-01-01

    We present the conformal behavior of the shear viscosity-to-entropy density ratio and the fermion-number diffusion coefficient within the perturbative regime of the conformal window for gauge-fermion theories.......We present the conformal behavior of the shear viscosity-to-entropy density ratio and the fermion-number diffusion coefficient within the perturbative regime of the conformal window for gauge-fermion theories....

  13. SU-E-T-389: Evaluation of Flattening-Filter-Free Arcs for Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, L; Lee, H; Pompos, A; Yan, Y; Jiang, S; Foster, R [UT Southwestern Medical Center, Dallas, TX (United States)

    2015-06-15

    Purpose: To evaluate dynamic conformal arc therapy (DCAT) and volumetric-modulated arc therapy (VMAT) using flattening-filter-free (FFF) beams for treating non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT). Methods: Five clinical patients, previously treated with SBRT using non-coplanar 3D conformal radiation therapy (3DCRT), were selected and re-planned with DCAT and VMAT with both FFF beam (6xFFF with a dose rate of 1200MU/min) and flattened beams (6x with 600 MU/min). All the arc plans were planned with one 360° arc and normalized to the same PTV coverage (100% prescription cover 95% PTV volume) for comparison. Treatment planning metrics such as R100%, R50%, D2cm and lung V20 were compared to the original plans. To evaluate the treatment efficiency differences, all the arc plans were delivered and plan delivery time was compared to that of the clinical treatment as recorded in Mosaiq. Results: All plans meet RTOG conformality constraints and normal tissue tolerances. Average R100% was similar for FFFDCAT (1.07±0.05), FFFVMAT (1.03±0.08) and flattened VMAT (fVMAT) (1.03±0.09) while flattened DCAT (fDCAT) (1.09±0.07) and 3DCRT (1.11±0.06) were significantly inferior (p<0.05, t test). FFFDCAT produced the best average intermediate dose conformality as indicated by R50% (3.86±0.44) and D2cm (43.7±5.3%) when compared to all the other techniques. Significant improvement (p<0.05) in lung V20 was also found with FFFDCAT (2.33±2.06%) when compared to FFFVMAT (2.48±2.03%), fVMAT (2.52±2.07%) and fDCAT (2.64±2.11%) and was slightly better than 3DCRT (2.43±2.04%), though not significant. The FFFDCAT delivery significantly improves the treatment efficiency with an average plan delivery time of 2.70±1.57 min (p<0.05), as compared to fDCAT (5.98±3.45min), fVMAT (6.51±2.94) and 3DCRT (25.14±5.67), but is not significantly better than the FFFVMAT (3.18±1.04). Conclusion: Combining FFF beams and DCAT provide promising

  14. Motion of polar cap arcs

    Science.gov (United States)

    Hosokawa, K.; Moen, J. I.; Shiokawa, K.; Otsuka, Y.

    2011-01-01

    A statistics of motion of polar cap arcs is conducted by using 5 years of optical data from an all-sky imager at Resolute Bay, Canada (74.73°N, 265.07°E). We identified 743 arcs by using an automated arc detection algorithm and statistically examined their moving velocities as estimated by the method of Hosokawa et al. (2006). The number of the arcs studied is about 5 times larger