WorldWideScience

Sample records for dynamic conformal arc

  1. TH-EF-BRB-04: 4π Dynamic Conformal Arc Therapy Dynamic Conformal Arc Therapy (DCAT) for SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, T; Long, T; Tian, Z.; Yan, Y; Jiang, S; Gu, X [UT Southwestern Medical Center, Dallas, TX (United States); Modiri, A; Sawant, A [University of Maryland in Baltimore, Baltimore, MD (United States)

    2016-06-15

    Purpose: To develop an efficient and effective trajectory optimization methodology for 4π dynamic conformal arc treatment (4π DCAT) with synchronized gantry and couch motion; and to investigate potential clinical benefits for stereotactic body radiation therapy (SBRT) to breast, lung, liver and spine tumors. Methods: The entire optimization framework for 4π DCAT inverse planning consists of two parts: 1) integer programming algorithm and 2) particle swarm optimization (PSO) algorithm. The integer programming is designed to find an optimal solution for arc delivery trajectory with both couch and gantry rotation, while PSO minimize a non-convex objective function based on the selected trajectory and dose-volume constraints. In this study, control point interaction is explicitly taken into account. Beam trajectory was modeled as a series of control points connected together to form a deliverable path. With linear treatment planning objectives, a mixed-integer program (MIP) was formulated. Under mild assumptions, the MIP is tractable. Assigning monitor units to control points along the path can be integrated into the model and done by PSO. The developed 4π DCAT inverse planning strategy is evaluated on SBRT cases and compared to clinically treated plans. Results: The resultant dose distribution of this technique was evaluated between 3D conformal treatment plan generated by Pinnacle treatment planning system and 4π DCAT on a lung SBRT patient case. Both plans share the same scale of MU, 3038 and 2822 correspondingly to 3D conformal plan and 4π DCAT. The mean doses for most of OARs were greatly reduced at 32% (cord), 70% (esophagus), 2.8% (lung) and 42.4% (stomach). Conclusion: Initial results in this study show the proposed 4π DCAT treatment technique can achieve better OAR sparing and lower MUs, which indicates that the developed technique is promising for high dose SBRT to reduce the risk of secondary cancer.

  2. Conformity of LINAC-Based Stereotactic Radiosurgery Using Dynamic Conformal Arcs and Micro-Multileaf Collimator

    International Nuclear Information System (INIS)

    Hazard, Lisa J.; Wang, Brian; Skidmore, Thomas B.; Chern, Shyh-Shi; Salter, Bill J.; Jensen, Randy L.; Shrieve, Dennis C.

    2009-01-01

    Purpose: To assess the conformity of dynamic conformal arc linear accelerator-based stereotactic radiosurgery and to describe a standardized method of isodose surface (IDS) selection. Methods and Materials: In 174 targets, the conformity index (CI) at the prescription IDS used for treatment was calculated as CI = (PIV/PVTV)/(PVTV/TV), where TV is the target volume, PIV (prescription isodose volume) is the total volume encompassed by the prescription IDS, and PVTV is the TV encompassed by the IDS. In addition, a 'standardized' prescription IDS (sIDS) was chosen according to the following criteria: 95% of the TV was encompassed by the PIV and 99% of TV was covered by 95% of the prescription dose. The CIs at the sIDS were also calculated. Results: The median CI at the prescription IDS and sIDS was 1.63 and 1.47, respectively (p < 0.001). In 132 of 174 cases, the volume of normal tissue in the PIV was reduced by the prescription to the sIDS compared with the prescription IDS, in 20 cases it remained unchanged, and in 22 cases it was increased. Conclusion: The CIs obtained with linear accelerator-based stereotactic radiosurgery are comparable to those previously reported for gamma knife stereotactic radiosurgery. Using a uniform method to select the sIDS, adequate target coverage was usually achievable with prescription to an IDS greater than that chosen by the treating physician (prescription IDS), providing sparing of normal tissue. Thus, the sIDS might aid physicians in identifying a prescription IDS that balances coverage and conformity

  3. 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.

  4. Dosimetric Impact of Primary Planning Parameters in Dynamic Conformal Arc Technique for Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Yeon; Suh, Tae Suk [Dept. of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Si Yong [Dept. of Radiation Oncology, Mayo Clinic, Jacksonvile (United States); Lee, Jeong Woo [Dept. of Radiation Oncology, Konkuk University Medical Center, Seoul (Korea, Republic of); Choi, Kyoung Sik [Dept. of Radiation Oncology, Anyang SAM Hospital, Anyang (Korea, Republic of)

    2011-04-15

    As one of the stereotactic body radiation therapy (SBRT) techniques, dynamic conformal arc therapy (DCAT) is commonly adopted to efficiently deliver conformal doses. However, as the DCAT uses numerous beams at individual control points, the dosimetric errors generated from each beam can be accumulated and manifested. In SBRT, therefore, due to the high fractional dose within a few fractions to moving target, the determination of the applied plan parameters can be critical and the evaluation of dosimetric impact of planning parameters would play an important role in DCAT planning process. In this study, we systematically evaluated the dosimetric influence caused by the variable grid size and the angular increment in DCAT for lung SBRT. Dose variations with different parameters were estimated for spherical and elongated tumors on an anthropomorphic phantom. The systematic analysis of the generated dose variation would guide to determine appropriate plan parameters and to estimate the dose errors in planning process in a clinical perspective of DCAT. It was found that two plan parameters, grid size and angular increment, in DCAT could cause non-negligible dose uncertainty. Coarse grid size led patients to get unnecessary overdose. Coarse angular increment could make significantly inaccurate prediction of OAR dose, resulting in either over- or under- estimation depending on the location of OAR relative to the isocenter.

  5. Dosimetric Comparison of Helical Tomotherapy and Dynamic Conformal Arc Therapy in Stereotactic Radiosurgery for Vestibular Schwannomas

    International Nuclear Information System (INIS)

    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

  6. Comparative dosimetric study of three-dimensional conformal, dynamic conformal arc, and intensity-modulated radiotherapy for brain tumor treatment using Novalis system

    International Nuclear Information System (INIS)

    Ding Meisong; Newman, Francis M.S.; Kavanagh, Brian D.; Stuhr, Kelly M.S.; Johnson, Tim K.; Gaspar, Laurie E.

    2006-01-01

    Purpose: To investigate the dosimetric differences among three-dimensional conformal radiotherapy (3D-CRT), dynamic conformal arc therapy (DCAT), and intensity-modulated radiotherapy (IMRT) for brain tumor treatment. Methods and Materials: Fifteen patients treated with Novalis were selected. We performed 3D-CRT, DCAT, and IMRT plans for all patients. The margin for the planning target volume (PTV) was 1 mm, and the specific prescription dose was 90% for all plans. The target coverage at the prescription dose, conformity index (CI), and heterogeneity index were analyzed for all plans. Results: For small tumors (PTV ≤2 cm 3 ), the three dosimetric parameters had approximate values for both 3D-CRT and DCAT plans. The CI for the IMRT plans was high. For medium tumors (PTV >2 to ≤100 cm 3 ), the three plans were competitive with each other. The IMRT plans had a greater CI, better target coverage at the prescription dose, and a better heterogeneity index. For large tumors (PTV >100 cm 3 ), the IMRT plan had good target coverage at the prescription dose and heterogeneity index and approximate CI values as those in the 3D-CRT and DCAT plans. Conclusion: The results of our study have shown that DCAT is suitable for most cases in the treatment of brain tumors. For a small target, 3D-CRT is useful, and IMRT is not recommended. For larger tumors, IMRT is superior to 3D-CRT and very competitive in sparing critical structures, especially for big tumors

  7. Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcsDosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs.

    Science.gov (United States)

    Liu, Haisong; Li, Jun; Pappas, Evangelos; Andrews, David; Evans, James; Werner-Wasik, Maria; Yu, Yan; Dicker, Adam; Shi, Wenyin

    2016-09-08

    An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 ± 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the

  8. Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

    International Nuclear Information System (INIS)

    Jereczek-Fossa, Barbara A.; Vavassori, Andrea; Fodor, Cristiana; Santoro, Luigi; Zerini, Dario; Cattani, Federica; Garibaldi, Cristina; Cambria, Raffaella; Fodor, Andrei; Boboc, Genoveva Ionela; Vitolo, Viviana; Ivaldi, Giovanni Battista; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto

    2008-01-01

    Purpose: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. Methods and Materials: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. Results: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p 0.04, respectively). The negative effect of dose >76 Gy was not observed (p 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. Conclusions: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer

  9. 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

    International Nuclear Information System (INIS)

    Uto, Megumi; Mizowaki, Takashi; Ogura, Kengo; Hiraoka, Masahiro

    2016-01-01

    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 beams. While the use of non-coplanar beams in volumetric-modulated arc therapy (VMAT) of malignant intracranial tumors has recently been reported, no dosimetric comparison has yet been made between VMAT using non-coplanar arcs (ncVMAT) and VMAT employing only coplanar arcs (coVMAT) among patients with craniopharyngiomas. We performed a planning study comparing dose distributions to the PTV, hippocampus, and other organs at risk (OAR) of dynamic conformal arc therapy (DCAT), coVMAT, and ncVMAT. DCAT, coVMAT, and ncVMAT plans were created for 10 patients with craniopharyngiomas. The prescription dose was 52.2 Gy in 29 fractions, and 99 % of each PTV was covered by 90 % of the prescribed dose. The maximum dose was held below 107 % of the prescribed dose. CoVMAT and ncVMAT plans were formulated to satisfy the following criteria: the doses to the hippocampus were minimized, and the doses to the OAR were similar to or lower than those of DCAT. The mean equivalent doses in 2-Gy fractions to 40 % of the volumes of the bilateral hippocampus [EQD 2 (40% hippos )] were 15.4/10.8/6.5 Gy for DCAT/coVMAT/ncVMAT, respectively. The EQD 2 (40% hippos ) for ncVMAT were <7.3 Gy, which is the threshold predicting cognitive impairment, as defined by Gondi et al.. The mean doses to normal brain tissue and the conformity indices were similar for the three plans, and the homogeneity indices were significantly better for coVMAT and ncVMAT compared with DCAT. NcVMAT is more appropriate than DCAT and coVMAT for

  10. Generative Models of Conformational Dynamics

    OpenAIRE

    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...

  11. 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. PMID:24446358

  12. Electric arc behaviour in dynamic magnetic fields

    International Nuclear Information System (INIS)

    Put'ko, V.F.

    2000-01-01

    The behaviour of an electric arc in different time-dependent (dynamic) magnetic fields was investigated. New possibilities were found for spatial and energy stabilisation of a discharge, for intensifying heat exchange, extending the electric arc and distributed control of electric arc plasma. Rotating, alternating and travelling magnetic fields were studied. It was found that under the effect of a relatively low frequency of variations of dynamic magnetic fields (f 1000 Hz) the arc stabilised at the axis of the discharge chamber, the pulsation level decreased and discharge stability increased. The borders between these two arc existence modes were formed by a certain critical field variation frequency the period of which was determined by the heat relaxation time of the discharge. (author)

  13. Optimal set of grid size and angular increment for practical dose calculation using the dynamic conformal arc technique: a systematic evaluation of the dosimetric effects in lung stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Park, Ji-Yeon; Kim, Siyong; Park, Hae-Jin; Lee, Jeong-Woo; Kim, Yeon-Sil; Suh, Tae-Suk

    2014-01-01

    To recommend the optimal plan parameter set of grid size and angular increment for dose calculations in treatment planning for lung stereotactic body radiation therapy (SBRT) using dynamic conformal arc therapy (DCAT) considering both accuracy and computational efficiency. Dose variations with varying grid sizes (2, 3, and 4 mm) and angular increments (2°, 4°, 6°, and 10°) were analyzed in a thorax phantom for 3 spherical target volumes and in 9 patient cases. A 2-mm grid size and 2° angular increment are assumed sufficient to serve as reference values. The dosimetric effect was evaluated using dose–volume histograms, monitor units (MUs), and dose to organs at risk (OARs) for a definite volume corresponding to the dose–volume constraint in lung SBRT. The times required for dose calculations using each parameter set were compared for clinical practicality. Larger grid sizes caused a dose increase to the structures and required higher MUs to achieve the target coverage. The discrete beam arrangements at each angular increment led to over- and under-estimated OARs doses due to the undulating dose distribution. When a 2° angular increment was used in both studies, a 4-mm grid size changed the dose variation by up to 3–4% (50 cGy) for the heart and the spinal cord, while a 3-mm grid size produced a dose difference of <1% (12 cGy) in all tested OARs. When a 3-mm grid size was employed, angular increments of 6° and 10° caused maximum dose variations of 3% (23 cGy) and 10% (61 cGy) in the spinal cord, respectively, while a 4° increment resulted in a dose difference of <1% (8 cGy) in all cases except for that of one patient. The 3-mm grid size and 4° angular increment enabled a 78% savings in computation time without making any critical sacrifices to dose accuracy. A parameter set with a 3-mm grid size and a 4° angular increment is found to be appropriate for predicting patient dose distributions with a dose difference below 1% while reducing the

  14. Dynamical interpretation of nonrelativistic conformal groups

    International Nuclear Information System (INIS)

    Andrzejewski, K.; Gonera, J.

    2013-01-01

    It is shown that N-Galilean conformal algebra with N odd and nontrivial central charge is the maximal symmetry algebra for higher derivative free theory both on classical and quantum levels. By maximal symmetry algebra the Lie algebra of the maximal group of space–time symmetry transformations is understood which preserves higher order free dynamics

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

    International Nuclear Information System (INIS)

    Jiang, R; Zhan, L; Osei, E

    2015-01-01

    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

  16. Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

    Science.gov (United States)

    Song, Wei; Guo, Jun-Tao

    2015-01-01

    Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

  17. Comparison of static conformal field with multiple noncoplanar arc techniques for stereotactic radiosurgery or stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Hamilton, Russell J.; Kuchnir, Franca T.; Sweeney, Patrick; Rubin, Steven J.; Dujovny, Manuel; Pelizzari, Charles A.; Chen, George T. Y.

    1995-01-01

    Purpose: Compare the use of static conformal fields with the use of multiple noncoplanar arcs for stereotactic radiosurgery or stereotactic radiotherapy treatment of intracranial lesions. Evaluate the efficacy of these treatment techniques to deliver dose distributions comparable to those considered acceptable in current radiotherapy practice. Methods and Materials: A previously treated radiosurgery case of a patient presenting with an irregularly shaped intracranial lesion was selected. Using a three-dimensional (3D) treatment-planning system, treatment plans using a single isocenter multiple noncoplanar arc technique and multiple noncoplanar conformal static fields were generated. Isodose distributions and dose volume histograms (DVHs) were computed for each treatment plan. We required that the 80% (of maximum dose) isodose surface enclose the target volume for all treatment plans. The prescription isodose was set equal to the minimum target isodose. The DVHs were analyzed to evaluate and compare the different treatment plans. Results: The dose distribution in the target volume becomes more uniform as the number of conformal fields increases. The volume of normal tissue receiving low doses (> 10% of prescription isodose) increases as the number of static fields increases. The single isocenter multiple arc plan treats the greatest volume of normal tissue to low doses, approximately 1.6 times more volume than that treated by four static fields. The volume of normal tissue receiving high (> 90% of prescription isodose) and intermediate (> 50% of prescription isodose) doses decreases by 29 and 22%, respectively, as the number of static fields is increased from four to eight. Increasing the number of static fields to 12 only further reduces the high and intermediate dose volumes by 10 and 6%, respectively. The volume receiving the prescription dose is more than 3.5 times larger than the target volume for all treatment plans. Conclusions: Use of a multiple noncoplanar

  18. The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility.

    Science.gov (United States)

    Wall, Mark J; Collins, Dawn R; Chery, Samantha L; Allen, Zachary D; Pastuzyn, Elissa D; George, Arlene J; Nikolova, Viktoriya D; Moy, Sheryl S; Philpot, Benjamin D; Shepherd, Jason D; Müller, Jürgen; Ehlers, Michael D; Mabb, Angela M; Corrêa, Sonia A L

    2018-05-24

    Neuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasome-dependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Proton Arc Reduces Range Uncertainty Effects and Improves Conformality Compared With Photon Volumetric Modulated Arc Therapy in Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seco, Joao, E-mail: jseco@partners.org [Francis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gu, Guan; Marcelos, Tiago; Kooy, Hanne; Willers, Henning [Francis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: To describe, in a setting of non-small cell lung cancer (NSCLC), the theoretical dosimetric advantages of proton arc stereotactic body radiation therapy (SBRT) in which the beam penumbra of a rotating beam is used to reduce the impact of range uncertainties. Methods and Materials: Thirteen patients with early-stage NSCLC treated with proton SBRT underwent repeat planning with photon volumetric modulated arc therapy (Photon-VMAT) and an in-house-developed arc planning approach for both proton passive scattering (Passive-Arc) and intensity modulated proton therapy (IMPT-Arc). An arc was mimicked with a series of beams placed at 10° increments. Tumor and organ at risk doses were compared in the context of high- and low-dose regions, represented by volumes receiving >50% and <50% of the prescription dose, respectively. Results: In the high-dose region, conformality index values are 2.56, 1.91, 1.31, and 1.74, and homogeneity index values are 1.29, 1.22, 1.52, and 1.18, respectively, for 3 proton passive scattered beams, Passive-Arc, IMPT-Arc, and Photon-VMAT. Therefore, proton arc leads to a 30% reduction in the 95% isodose line volume to 3-beam proton plan, sparing surrounding organs, such as lung and chest wall. For chest wall, V30 is reduced from 21 cm{sup 3} (3 proton beams) to 11.5 cm{sup 3}, 12.9 cm{sup 3}, and 8.63 cm{sup 3} (P=.005) for Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. In the low-dose region, the mean lung dose and V20 of the ipsilateral lung are 5.01 Gy(relative biological effectiveness [RBE]), 4.38 Gy(RBE), 4.91 Gy(RBE), and 5.99 Gy(RBE) and 9.5%, 7.5%, 9.0%, and 10.0%, respectively, for 3-beam, Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. Conclusions: Stereotactic body radiation therapy with proton arc and Photon-VMAT generate significantly more conformal high-dose volumes than standard proton SBRT, without loss of coverage of the tumor and with significant sparing of nearby organs, such as chest wall. In addition

  20. Conformational dynamics data bank: a database for conformational dynamics of proteins and supramolecular protein assemblies.

    Science.gov (United States)

    Kim, Do-Nyun; Altschuler, Josiah; Strong, Campbell; McGill, Gaël; Bathe, Mark

    2011-01-01

    The conformational dynamics data bank (CDDB, http://www.cdyn.org) is a database that aims to provide comprehensive results on the conformational dynamics of high molecular weight proteins and protein assemblies. Analysis is performed using a recently introduced coarse-grained computational approach that is applied to the majority of structures present in the electron microscopy data bank (EMDB). Results include equilibrium thermal fluctuations and elastic strain energy distributions that identify rigid versus flexible protein domains generally, as well as those associated with specific functional transitions, and correlations in molecular motions that identify molecular regions that are highly coupled dynamically, with implications for allosteric mechanisms. A practical web-based search interface enables users to easily collect conformational dynamics data in various formats. The data bank is maintained and updated automatically to include conformational dynamics results for new structural entries as they become available in the EMDB. The CDDB complements static structural information to facilitate the investigation and interpretation of the biological function of proteins and protein assemblies essential to cell function.

  1. Arc dynamics of a pulsed DC nitrogen rotating gliding arc discharge

    Science.gov (United States)

    Zhu, Fengsen; Zhang, Hao; Li, Xiaodong; Wu, Angjian; Yan, Jianhua; Ni, Mingjiang; Tu, Xin

    2018-03-01

    In this study, a novel pulsed direct current (DC) rotating gliding arc (RGA) plasma reactor co-driven by an external magnetic field and a tangential gas flow has been developed. The dynamic characteristics of the rotating gliding arc have been investigated by means of numerical simulation and experiment. The simulation results show that a highly turbulent vortex flow can be generated at the bottom of the RGA reactor to accelerate the arc rotation after arc ignition, whereas the magnitude of gas velocity declined significantly along the axial direction of the RGA reactor. The calculated arc rotation frequency (14.4 Hz) is reasonably close to the experimental result (18.5 Hz) at a gas flow rate of 10 l min-1. In the presence of an external magnet, the arc rotation frequency is around five times higher than that of the RGA reactor without using a magnet, which suggests that the external magnetic field plays a dominant role in the maintenance of the arc rotation in the upper zone of the RGA reactor. In addition, when the magnet is placed outside the reactor reversely to form a reverse external magnetic field, the arc can be stabilized at a fixed position in the inner wall of the outer electrode at a critical gas flow rate of 16 l min-1.

  2. Image-guided conformation arc therapy for prostate cancer: Early side effects

    International Nuclear Information System (INIS)

    Soete, Guy; Verellen, Dirk; Michielsen, Dirk; Rappe, Bernard; Keuppen, Frans; Storme, Guy

    2006-01-01

    Purpose: To evaluate early side effects in prostate cancer patients treated with image-guided conformation arc therapy (IGCAT) using a minimultileaf collimator and daily X-ray-assisted patient positioning. Methods and Materials: Between May 2000 and November 2004, 238 cT1-T3N0M0 tumors were treated with doses of 70 or 78 Gy. Seventy patients also received neoadjuvant or concurrent hormonal treatment. Median follow-up is 18 months (range, 4-55 months). Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity scoring system was used to evaluate early side effects. Results: Grade 1, 2, and >2 acute side effects occurred in 19, 6, and 0% (gastrointestinal) and 37, 16, and 0% (genitourinary) of the patients. No relation between radiation dose and early side effects was observed. Conclusion: Patients treated with image-guided conformation arc therapy experience a low rate of Grade 2 (i.e., requiring medication) early side effects. The definitive evaluation of late side effects and biochemical control requires further follow-up

  3. Dynamic electron arc radiotherapy (DEAR): a feasibility study

    International Nuclear Information System (INIS)

    Rodrigues, Anna; Yin, Fang-Fang; Wu, Qiuwen

    2014-01-01

    Compared to other radiation therapy modalities, clinical electron beam therapy has remained practically unchanged for the past few decades even though electron beams with multiple energies are widely available on most linacs. In this paper, we present the concept of dynamic electron arc radiotherapy (DEAR), a new conformal electron therapy technique with synchronized couch motion. DEAR utilizes combination of gantry rotation, couch motion, and dose rate modulation to achieve desirable dose distributions in patient. The electron applicator is kept to minimize scatter and maintain narrow penumbra. The couch motion is synchronized with the gantry rotation to avoid collision between patient and the electron cone. In this study, we investigate the feasibility of DEAR delivery and demonstrate the potential of DEAR to improve dose distributions on simple cylindrical phantoms. DEAR was delivered on Varian's TrueBeam linac in Research Mode. In conjunction with the recorded trajectory log files, mechanical motion accuracies and dose rate modulation precision were analyzed. Experimental and calculated dose distributions were investigated for different energies (6 and 9 MeV) and cut-out sizes (1×10 cm 2  and 3×10 cm 2  for a 15×15 cm 2  applicator). Our findings show that DEAR delivery is feasible and has the potential to deliver radiation dose with high accuracy (root mean square error, or RMSE of <0.1 MU, <0.1° gantry, and <0.1 cm couch positions) and good dose rate precision (1.6 MU min −1 ). Dose homogeneity within ±2% in large and curved targets can be achieved while maintaining penumbra comparable to a standard electron beam on a flat surface. Further, DEAR does not require fabrication of patient-specific shields. These benefits make DEAR a promising technique for conformal radiotherapy of superficial tumors. (paper)

  4. Conformational analysis of oligosaccharides and polysaccharides using molecular dynamics simulations.

    Science.gov (United States)

    Frank, Martin

    2015-01-01

    Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).

  5. Is DNA a nonlinear dynamical system where solitary conformational ...

    Indian Academy of Sciences (India)

    Unknown

    DNA is considered as a nonlinear dynamical system in which solitary conformational waves can be excited. The ... nonlinear differential equations and their soliton-like solu- .... structure and dynamics can be added till the most accurate.

  6. Conformation analysis of trehalose. Molecular dynamics simulation and molecular mechanics

    International Nuclear Information System (INIS)

    Donnamaira, M.C.; Howard, E.I.; Grigera, J.R.

    1992-09-01

    Conformational analysis of the disaccharide trehalose is done by molecular dynamics and molecular mechanics. In spite of the different force fields used in each case, comparison between the molecular dynamics trajectories of the torsional angles of glycosidic linkage and energy conformational map shows a good agreement between both methods. By molecular dynamics it is observed a moderate mobility of the glycosidic linkage. The demands of computer time is comparable in both cases. (author). 6 refs, 4 figs

  7. 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...

  8. 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...

  9. Multitasking the code ARC3D. [for computational fluid dynamics

    Science.gov (United States)

    Barton, John T.; Hsiung, Christopher C.

    1986-01-01

    The CRAY multitasking system was developed in order to utilize all four processors and sharply reduce the wall clock run time. This paper describes the techniques used to modify the computational fluid dynamics code ARC3D for this run and analyzes the achieved speedup. The ARC3D code solves either the Euler or thin-layer N-S equations using an implicit approximate factorization scheme. Results indicate that multitask processing can be used to achieve wall clock speedup factors of over three times, depending on the nature of the program code being used. Multitasking appears to be particularly advantageous for large-memory problems running on multiple CPU computers.

  10. Molecular dynamics studies of the conformation of sorbitol

    Science.gov (United States)

    Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

    2009-01-01

    Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

  11. Comparing conformal, arc radiotherapy and helical tomotherapy in craniospinal irradiation planning.

    Science.gov (United States)

    Myers, Pamela A; Mavroidis, Panayiotis; Papanikolaou, Nikos; Stathakis, Sotirios

    2014-09-08

    Currently, radiotherapy treatment plan acceptance is based primarily on dosimetric performance measures. However, use of radiobiological analysis to assess benefit in terms of tumor control and harm in terms of injury to normal tissues can be advantageous. For pediatric craniospinal axis irradiation (CSI) patients, in particular, knowing the technique that will optimize the probabilities of benefit versus injury can lead to better long-term outcomes. Twenty-four CSI pediatric patients (median age 10) were retrospectively planned with three techniques: three-dimensional conformal radiation therapy (3D CRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). VMAT plans consisted of one superior and one inferior full arc, and tomotherapy plans were created using a 5.02cm field width and helical pitch of 0.287. Each plan was normalized to 95% of target volume (whole brain and spinal cord) receiving prescription dose 23.4Gy in 13 fractions. Using an in-house MATLAB code and DVH data from each plan, the three techniques were evaluated based on biologically effective uniform dose (D=), the complication-free tumor control probability (P+), and the width of the therapeutically beneficial range. Overall, 3D CRT and VMAT plans had similar values of D= (24.1 and 24.2 Gy), while HT had a D= slightly lower (23.6 Gy). The average values of the P+ index were 64.6, 67.4, and 56.6% for 3D CRT, VMAT, and HT plans, respectively, with the VMAT plans having a statistically significant increase in P+. Optimal values of D= were 28.4, 33.0, and 31.9 Gy for 3D CRT, VMAT, and HT plans, respectively. Although P+ values that correspond to the initial dose prescription were lower for HT, after optimizing the D= prescription level, the optimal P+ became 94.1, 99.5, and 99.6% for 3D CRT, VMAT, and HT, respectively, with the VMAT and HT plans having statistically significant increases in P+. If the optimal dose level is prescribed using a radiobiological evaluation method, as

  12. Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Barry J Grant

    2009-03-01

    Full Text Available Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly populated intermediate structures. These structures have unique switch orientations (residues 25-40 and 57-75 intermediate between GTP and GDP states, or distinct loop3 (46-49, loop7 (105-110, and alpha5 C-terminus (159-166 conformations distal from the nucleotide-binding site. In addition, these barrier-crossing trajectories predict novel nucleotide-dependent correlated motions, including correlations of alpha2 (residues 66-74 with alpha3-loop7 (93-110, loop2 (26-37 with loop10 (145-151, and loop3 (46-49 with alpha5 (152-167. The interconversion between newly identified Ras conformations revealed by this study advances our mechanistic understanding of Ras function. In addition, the pattern of correlated motions provides new evidence for a dynamic linkage between the nucleotide-binding site and the membrane interacting C-terminus critical for the signaling function of Ras. Furthermore, normal mode analysis indicates that the dominant collective motion that occurs during nucleotide-dependent conformational exchange, and captured in aMD (but absent in cMD simulations, is a low-frequency motion intrinsic to the structure.

  13. Dynamical realizations of l-conformal Newton–Hooke group

    International Nuclear Information System (INIS)

    Galajinsky, Anton; Masterov, Ivan

    2013-01-01

    The method of nonlinear realizations and the technique previously developed in [A. Galajinsky, I. Masterov, Nucl. Phys. B 866 (2013) 212, (arXiv:1208.1403)] are used to construct a dynamical system without higher derivative terms, which holds invariant under the l-conformal Newton–Hooke group. A configuration space of the model involves coordinates, which parametrize a particle moving in d spatial dimensions and a conformal mode, which gives rise to an effective external field. The dynamical system describes a generalized multi-dimensional oscillator, which undergoes accelerated/decelerated motion in an ellipse in accord with evolution of the conformal mode. Higher derivative formulations are discussed as well. It is demonstrated that the multi-dimensional Pais–Uhlenbeck oscillator enjoys the l=3/2 -conformal Newton–Hooke symmetry for a particular choice of its frequencies

  14. Dosimetric study comparing volumetric arc modulation with RapidArc and fixed dynamic intensity-modulated radiation therapy for breast cancer radiotherapy after breast-conserving surgery

    International Nuclear Information System (INIS)

    Tie Jian; Sun Yan; Gong Jian; Han Shukui; Jiang Fan; Wu Hao

    2011-01-01

    Objective: To compare the dosimetric difference between volumetric are modulation with RapidArc and fixed field dynamic IMRT for breast cancer radiotherapy after breast-conserving surgery. Methods: Twenty patients with early left-sided breast cancer received radiotherapy after breast-conserving surgery. After target definition, treatment planning was performed by RapidArc and two fixed fields dynamic IMRT respectively on the same CT scan. The target dose distribution, homogeneity of the breast, and the irradiation dose and volume for the lungs, heart, and contralateral breast were read in the dose-volume histogram (DVH) and compared between RapidArc and IMRT. The treatment delivery time and monitor units were also compared. Results: In comparison with the IMRT planning,the homogeneity of clinical target volume (CTV), the volume proportion of 95% prescribed dose (V 95% ) was significantly higher by 0.65% in RapidArc (t=5.16, P=0.001), and the V 105% and V 110% were lower by 10.96% and 1.48 % respectively, however, without statistical significance (t=-2.05, P=0.055 and t=-1.33, P=0.197). The conformal index of planning target volume (PTV) by the RapidArc planning was (0.88±0.02), significantly higher than that by the IMRT planning [(0.74±0.03), t=18.54, P<0.001]. The homogeneity index (HI) of PTV by the RapidArc planning was 1.11±0.01, significantly lower than that by the IMRT planning (1.12±0.02, t=-2.44, P=0.02). There were no significant differences in the maximum dose (D max ) and V 20 for the ipsilateral lung between the RapidArc and IMRT planning, but the values of V 10 , V 5 , D min and D mean by RapidArc planning were all significantly higher than those by the IMRT planning (all P<0.01). The values of max dose and V 30 for the heart were similar by both techniques, but the values of V 10 and V 5 by the RapidArc planning were significantly higher (by 18% and 50%, respectively). The V 5 of the contralateral breast and lung by the RapidArc planning were

  15. Dynamic voltage-current characteristics for a water jet plasma arc

    International Nuclear Information System (INIS)

    Yang Jiaxiang; Lan Sheng; Xu Zuoming

    2008-01-01

    A virtual instrument technology is used to measure arc current, arc voltage, dynamic V-I characteristics, and nonlinear conductance for a cone-shaped water jet plasma arc under ac voltage. Experimental results show that ac arc discharge mainly happens in water vapor evaporated from water when heated. However, due to water's cooling effect and its conductance, arc conductance, reignition voltage, extinguish voltage, and current zero time are very different from those for ac arc discharge in gas work fluid. These can be valuable to further studies on mechanism and characteristics of plasma ac discharge in water, and even in gas work fluid

  16. Dynamics of the conformal factor in 4D gravity

    International Nuclear Information System (INIS)

    Antoniadis, I.

    1993-01-01

    We argue that 4D gravity is drastically modified at distances larger than the horizon scale, due to the large infrared quantum fluctuations of the conformal part of the metric. The infrared dynamics of the conformal factor is generated by an effective action, induced by the trace anomaly of matter in curved space, analogous to the Polyakov action in two dimensions. The resulting effective scalar theory is renormalizable, and possesses a non-trivial, infrared stable fixed point, characterized by an anomalous scaling dimension of the conformal factor. We argue that this theory describes a large distance scale invariant phase of 4D gravity and provides a framework for a dynamical solution of the cosmological constant problem (author). 12 refs

  17. Conformational Dynamics of Thermus aquaticus DNA Polymerase I during Catalysis

    Science.gov (United States)

    Suo, Zucai

    2014-01-01

    Despite the fact that DNA polymerases have been investigated for many years and are commonly used as tools in a number of molecular biology assays, many details of the kinetic mechanism they use to catalyze DNA synthesis remain unclear. Structural and kinetic studies have characterized a rapid, pre-catalytic open-to-close conformational change of the Finger domain during nucleotide binding for many DNA polymerases including Thermus aquaticus DNA polymerase I (Taq Pol), a thermostable enzyme commonly used for DNA amplification in PCR. However, little has been done to characterize the motions of other structural domains of Taq Pol or any other DNA polymerase during catalysis. Here, we used stopped-flow Förster resonance energy transfer (FRET) to investigate the conformational dynamics of all five structural domains of the full-length Taq Pol relative to the DNA substrate during nucleotide binding and incorporation. Our study provides evidence for a rapid conformational change step induced by dNTP binding and a subsequent global conformational transition involving all domains of Taq Pol during catalysis. Additionally, our study shows that the rate of the global transition was greatly increased with the truncated form of Taq Pol lacking the N-terminal domain. Finally, we utilized a mutant of Taq Pol containing a de novo disulfide bond to demonstrate that limiting protein conformational flexibility greatly reduced the polymerization activity of Taq Pol. PMID:24931550

  18. Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin

    Directory of Open Access Journals (Sweden)

    Soichiro Kitazawa

    2017-08-01

    Full Text Available Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the salt bridge between K11 and E34 and the hydrogen bond between I36 and Q41, which are predicted to control the fluctuation between the basic folded state, N1, and the alternatively folded state, N2, of the protein, using high-pressure NMR spectroscopy. The E34A mutation, which disrupts the salt bridge, did not alter picosecond–to–nanosecond, microsecond–to–millisecond dynamic motions, and stability of the protein, while the Q41N mutation, which destabilizes the hydrogen bond, specifically amplified the N1–N2 conformational fluctuation and decreased stability. Based on the observed thermodynamic stabilities of the various conformational states, we showed that in the Q41N mutant, the N1 state is more significantly destabilized than the N2 state, resulting in an increase in the relative population of N2. Identifying the interactions controlling specific motions of a protein will facilitate molecular design to achieve functional dynamics beyond native state dynamics.

  19. SU-E-T-542: Comparison of Stereotactic Radiosurgery (SRS) of Brain Lesions Using Gamma Knife, VMAT, IMRT, and Conformal Arcs

    International Nuclear Information System (INIS)

    Li, S; Charpentier, P; Chan, P; Neicu, T; Miyamoto, C

    2014-01-01

    Purpose: To compare dose distributions in stereotactic radiation surgery of brain lesions using gamma Knife, VMAT, conformal arcs, and IMRT in order to provide an optimal treatment. Methods: Dose distributions from single shot of 4C model of Gamma Knife at the helmet collimation sizes of 4, 8, 14, and 18 mm in diameter were compared with full arcs with the square shapes of 4×4 (or 5×5), 8×8 (or 10×10), and spherical shapes of 16 or 20 mm in diameter using EDR3 films in the same gamma knife QA phantom. Plans for ten SRS cases with single and multiple lesions were created in gamma knife plans and Pinnacle plans. The external beam plans had enlarged field size by 2-mm and used single conformal full circle arc for solitary lesion and none coplanar arcs/beams for multiple lesions. Coverage, conformity index, dose to critical organs, and integral dose to the brain and nearby critical structures were compared on all plans. Structures and dose matrices were registered in a Velocity deformable image registration system. Results: Single full circle arc from Elekta beam-modulate MLC (4-mm leaf thickness) and agility MLC (5-mm leaf thickness) have larger penumbra and less flatness than that of Gamma Knife single shot. None-coplanar arcs or beams were required to achieve similar dose distribution. In general, Gamma Knife plans provided significant less integral dose than that of linac-based plans. Benefits of IMRT and VMAT versus gamma Knife and conformal arcs were not significant. Conclusion: Our dose measurement and treatment planning evaluation clearly demonstrated dose distribution differences amount current popular SRS modalities for small solitary and multiple brain lesions. The trend of using MLC shape beams or arcs to replace conventional cones should be revisited in order to keep lower integral dose if the late correlates with some radiation-induced side effects. Pilot grant from Elekta LLC

  20. SU-F-T-112: Long-Term Follow-Up of NSCLC Patients Treated with Lung SBRT Using the Modified Conformal Arc (MDCA) Planning Technique

    Energy Technology Data Exchange (ETDEWEB)

    Ku, E; Desai, A [Frank H Netter, MD, School of Medicine, North Haven, CT (United States); Fang, D; Lawrence, C; Iannuzzi, C; Shi, C [St. Vincent’s Medical Center, Bridgeport, CT (United States)

    2016-06-15

    Purpose: To assess long-term toxicity and primary tumor changes for Stage I/II non-small cell lung carcinoma (NSCLC) patients after treatment with lung SBRT using the modified dynamic conformal arc (MDCA) planning technique. Methods: Clinical and radiograph data from electronic health records of 15 NSCLC patients treated with lung SBRT utilizing the MDCA technique between October 2011 and July 2014 were retrospectively reviewed. MDCA uses a coplanar beam arrangement, patient body center for the beam isocenter, and six partial rotation conformal arcs to target the tumor. Radiation Therapy Oncology Group (RTOG) guidelines for treatment parameters were followed. Most patients received 5 radiation fractions (Range: 3 to 7 fractions) with 48 hours between each fraction. Median total dose was 60 Gy (range: 45 to 70 Gy). Results: Median follow-up was 18 months (range: 6–51 months). Median age was 72.5 years (range: 48–90 years). Post-treatment findings included fatigue (n = 5) and chronic chest wall pain (n=1). Seven patients reported respiratory symptoms, which included: cough (n = 4), dyspnea (n = 5), and hemoptysis (n = 1). No patients deaths or grade ≥4 toxicity were recorded. Radiographic scarring was seen on computed tomography (CT) imaging in 6 patients. Local control rate was 93.3% (n = 14) and 1 patient had local recurrence. Conclusion: Our results were very similar to RTOG 0236 findings reported by Timmerman et al. – our local control rate was 93.3% compared to their 3-year primary tumor control rate of 97.6%. Toxicity rates were also similar – RTOG 0236 constitutional symptoms and pulmonary/upper respiratory symptoms rates were 36.4% and 60.0%, respectively, while ours were 33.3% and 46.7%, respectively. We were limited by a small sample size and relatively short follow-up but our findings support the use of the MDCA technique for lung SBRT treatment of Stage I/II NSCLC.

  1. Conformal dynamics for electroweak symmetry breaking, from LHC to cosmology

    International Nuclear Information System (INIS)

    Sannino, Francesco

    2009-01-01

    Full text. I will first introduce dynamical electroweak symmetry breaking and then present how to resolve some of the long-standing problems using (near) conformal dynamics. In order to construct sensible extension of DEWSB I will then review the state-of-the-art of the phase diagram of gauge theories of fundamental interactions as function of the number of colors, flavors and matter representation. Finally I will introduce recent models known as minimal walking models and show how they lead to natural candidates of dark matter. (author)

  2. 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. 2010 Elsevier Inc. All rights reserved.

  3. Extracting Markov Models of Peptide Conformational Dynamics from Simulation Data.

    Science.gov (United States)

    Schultheis, Verena; Hirschberger, Thomas; Carstens, Heiko; Tavan, Paul

    2005-07-01

    A high-dimensional time series obtained by simulating a complex and stochastic dynamical system (like a peptide in solution) may code an underlying multiple-state Markov process. We present a computational approach to most plausibly identify and reconstruct this process from the simulated trajectory. Using a mixture of normal distributions we first construct a maximum likelihood estimate of the point density associated with this time series and thus obtain a density-oriented partition of the data space. This discretization allows us to estimate the transfer operator as a matrix of moderate dimension at sufficient statistics. A nonlinear dynamics involving that matrix and, alternatively, a deterministic coarse-graining procedure are employed to construct respective hierarchies of Markov models, from which the model most plausibly mapping the generating stochastic process is selected by consideration of certain observables. Within both procedures the data are classified in terms of prototypical points, the conformations, marking the various Markov states. As a typical example, the approach is applied to analyze the conformational dynamics of a tripeptide in solution. The corresponding high-dimensional time series has been obtained from an extended molecular dynamics simulation.

  4. Conformational dynamics of amyloid proteins at the aqueous interface

    Science.gov (United States)

    Armbruster, Matthew; Horst, Nathan; Aoki, Brendy; Malik, Saad; Soto, Patricia

    2013-03-01

    Amyloid proteins is a class of proteins that exhibit distinct monomeric and oligomeric conformational states hallmark of deleterious neurological diseases for which there are not yet cures. Our goal is to examine the extent of which the aqueous/membrane interface modulates the folding energy landscape of amyloid proteins. To this end, we probe the dynamic conformational ensemble of amyloids (monomer prion protein and Alzheimer's Ab protofilaments) interacting with model bilayers. We will present the results of our coarse grain molecular modeling study in terms of the existence of preferential binding spots of the amyloid to the bilayer and the response of the bilayer to the interaction with the amyloid. NSF Nebraska EPSCoR First Award

  5. Dynamics of DNA conformations and DNA-protein interaction

    DEFF Research Database (Denmark)

    Metzler, R.; Ambjörnsson, T.; Lomholt, Michael Andersen

    2005-01-01

    Optical tweezers, atomic force microscopes, patch clamping, or fluorescence techniques make it possible to study both the equilibrium conformations and dynamics of single DNA molecules as well as their interaction with binding proteins. In this paper we address the dynamics of local DNA...... denaturation (bubble breathing), deriving its dynamic response to external physical parameters and the DNA sequence in terms of the bubble relaxation time spectrum and the autocorrelation function of bubble breathing. The interaction with binding proteins that selectively bind to the DNA single strand exposed...... in a denaturation bubble are shown to involve an interesting competition of time scales, varying between kinetic blocking of protein binding up to full binding protein-induced denaturation of the DNA. We will also address the potential to use DNA physics for the design of nanosensors. Finally, we report recent...

  6. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Crowe, Scott B [Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland (Australia); Kairn, Tanya [Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland (Australia); Premion, Wesley Medical Centre, Brisbane, Queensland (Australia); Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T [Premion, Wesley Medical Centre, Brisbane, Queensland (Australia); Kenny, John [Australian Clinical Dosimetry Services, Australian Radiation Protection and Nuclear Safety Agency, Melbourne, Victoria (Australia); Langton, Christian M; Trapp, Jamie V [Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland (Australia)

    2013-12-15

    This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

  7. Latitudinal dynamics of SAR-arcs relative to the local time

    International Nuclear Information System (INIS)

    Alekseev, V.N.; Ievenko, I.B.

    1991-01-01

    In November-December, 1988, January-April, 1989-1990, at the Maymaga station in Yakutia according to spectrophotometric data 47 events of the occurrence of red stable middle-latitudinal arcs (SAR-arcs) were recorded. On the basis of these data the latitudinal dynamics of SAR-arcs was studied depending on the local time and geomagnetic disturbance level. The uniform equatorial shift of SAR arcs in the night time is noticed, and a sharp increase of the speed of this motion can be caused by the nonstationary character of the magnetospheric activity

  8. Dissecting the dynamic conformations of the metamorphic protein lymphotactin.

    Science.gov (United States)

    Harvey, Sophie R; Porrini, Massimiliano; Konijnenberg, Albert; Clarke, David J; Tyler, Robert C; Langridge-Smith, Patrick R R; MacPhee, Cait E; Volkman, Brian F; Barran, Perdita E

    2014-10-30

    A mass spectrometer provides an ideal laboratory to probe the structure and stability of isolated protein ions. Interrogation of each discrete mass/charge-separated species enables the determination of the intrinsic stability of a protein fold, gaining snapshots of unfolding pathways. In solution, the metamorphic protein lymphotactin (Ltn) exists in equilibrium between two distinct conformations, a monomeric (Ltn10) and a dimeric (Ltn40) fold. Here, we use electron capture dissociation (ECD) and drift tube ion mobility-mass spectrometry (DT IM-MS) to analyze both forms and use molecular dynamics (MD) to consider how the solution fold alters in a solvent-free environment. DT IM-MS reveals significant conformational flexibility for the monomer, while the dimer appears more conformationally restricted. These findings are supported by MD calculations, which reveal how salt bridges stabilize the conformers in vacuo. Following ECD experiments, a distinctive fragmentation pattern is obtained for both the monomer and dimer. Monomer fragmentation becomes more pronounced with increasing charge state especially in the disordered regions and C-terminal α-helix in the solution fold. Lower levels of fragmentation are seen in the β-sheet regions and in regions that contain salt bridges, identified by MD simulations. The lowest charge state of the dimer for which we obtain ECD data ([D+9H](9+)) exhibits extensive fragmentation with no relationship to the solution fold and has a smaller collision cross section (CCS) than charge states 10-13+, suggesting a "collapsed" encounter complex. Other charge states of the dimer, as for the monomer, are resistant to fragmentation in regions of β-sheets in the solution fold. This study provides evidence for preservation and loss of global fold and secondary structural elements, providing a tantalizing glimpse into the power of the emerging field of native top-down mass spectrometry.

  9. Dynamics and diffusive-conformational coupling in polymer bulk samples and surfaces: a molecular dynamics study

    International Nuclear Information System (INIS)

    Vree, C; Mayr, S G

    2010-01-01

    The impact of free surfaces on the mobility and conformational fluctuations of model polymer chains is investigated with the help of classical molecular dynamics simulations over a broad temperature range. Below a critical temperature, T*, similar to the critical temperature of the mode coupling theory, the center-of-mass displacements and temporal fluctuations of the radius of gyration of individual chains-as a fingerprint of structural reconfigurations-reveal a strong enhancement close to surfaces, while this effect diminishes with increasing temperature and observation time. Interpreting conformational fluctuations as a random walk in conformational space, identical activation enthalpies for structural reconfigurations and diffusion are obtained within the error bars in the bulk and at the surfaces, thus indicating a coupling of diffusive and conformational dynamics.

  10. Dynamics of organizational culture: Individual beliefs vs. social conformity.

    Science.gov (United States)

    Ellinas, Christos; Allan, Neil; Johansson, Anders

    2017-01-01

    The complex nature of organizational culture challenges our ability to infer its underlying dynamics from observational studies. Recent computational studies have adopted a distinctly different view, where plausible mechanisms are proposed to describe a wide range of social phenomena, including the onset and evolution of organizational culture. In this spirit, this work introduces an empirically-grounded, agent-based model which relaxes a set of assumptions that describes past work-(a) omittance of an individual's strive for achieving cognitive coherence; (b) limited integration of important contextual factors-by utilizing networks of beliefs and incorporating social rank into the dynamics. As a result, we illustrate that: (i) an organization may appear to be increasingly coherent in terms of its organizational culture, yet be composed of individuals with reduced levels of coherence; (ii) the components of social conformity-peer-pressure and social rank-are influential at different aggregation levels.

  11. 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.

  12. 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.

  13. 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.

  14. Global brain dynamics during social exclusion predict subsequent behavioral conformity.

    Science.gov (United States)

    Wasylyshyn, Nick; Hemenway Falk, Brett; Garcia, Javier O; Cascio, Christopher N; O'Donnell, Matthew Brook; Bingham, C Raymond; Simons-Morton, Bruce; Vettel, Jean M; Falk, Emily B

    2018-02-01

    Individuals react differently to social experiences; for example, people who are more sensitive to negative social experiences, such as being excluded, may be more likely to adapt their behavior to fit in with others. We examined whether functional brain connectivity during social exclusion in the fMRI scanner can be used to predict subsequent conformity to peer norms. Adolescent males (n = 57) completed a two-part study on teen driving risk: a social exclusion task (Cyberball) during an fMRI session and a subsequent driving simulator session in which they drove alone and in the presence of a peer who expressed risk-averse or risk-accepting driving norms. We computed the difference in functional connectivity between social exclusion and social inclusion from each node in the brain to nodes in two brain networks, one previously associated with mentalizing (medial prefrontal cortex, temporoparietal junction, precuneus, temporal poles) and another with social pain (dorsal anterior cingulate cortex, anterior insula). Using predictive modeling, this measure of global connectivity during exclusion predicted the extent of conformity to peer pressure during driving in the subsequent experimental session. These findings extend our understanding of how global neural dynamics guide social behavior, revealing functional network activity that captures individual differences.

  15. 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

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

    International Nuclear Information System (INIS)

    Burghelea, M; Poels, K; Gevaert, T; Tournel, K; Dhont, J; De Ridder, M; Verellen, D; Hung, C; Eriksson, K; Simon, V

    2015-01-01

    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

  17. 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...

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

    International Nuclear Information System (INIS)

    Coulombe, Sylvain

    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 -tilde1 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. oxide-contaminated cathode surface). Through an appropriate choice of the local probabilistic displacement rules, the model is able to correctly represent the dynamic behaviours of the type-A cathode spot, including the FPS for the arc elongation (i.e. voltage) and the arc erosion trace formation. The model illustrates that the cathode spot displacements between re-strikes can be seen as a diffusion process with a diffusion constant which depends on the surface structure. A physical interpretation for the jumping probability associated with the re-strike event is given in terms of the electron emission processes across dielectric contaminants present on the cathode surface

  19. Radioactive waste combustion-vitrification under arc plasma: thermal and dynamic modelling

    International Nuclear Information System (INIS)

    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)

  20. Radioactive waste combustion / vitrification under arc plasma: thermal and dynamic modelling

    International Nuclear Information System (INIS)

    Barthelemy, B.

    2003-01-01

    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)

  1. The superiority of hybrid-volumetric arc therapy (VMAT) technique over double arcs VMAT and 3D-conformal technique in the treatment of locally advanced non-small cell lung cancer – A planning study

    International Nuclear Information System (INIS)

    Chan, Oscar S.H.; Lee, Michael C.H.; Hung, Albert W.M.; Chang, Amy T.Y.; Yeung, Rebecca M.W.; Lee, Anne W.M.

    2011-01-01

    Purpose: To compare the dosimetric performance of three different treatment techniques – conformal radiotherapy (CRT), double arcs volumetric modulated arc therapy (RapidArc, RA) and Hybrid-RapidArc (H-RA) for locally-advanced non-small cell lung cancer (NSCLC). Material and methods: CRT, RA and H-RA plans were optimized for 24 stage III NSCLC patients. The target prescription dose was 60 Gy. CRT consisted of 5–7 coplanar fields, while RA comprised of two 204 o arcs. H-RA referred to two 204 o arcs plus 2 static fields, which accounted for approximately half of the total dose. The plans were optimized to fulfill the departmental plan acceptance criteria. Results: RA and H-RA yielded a 20% better conformity compared with CRT. Lung volume receiving >20 Gy (V20) and mean lung dose (MLD) were the lowest in H-RA (V20 1.7% and 2.1% lower, MLD 0.59 Gy and 0.41 Gy lower than CRT and RA respectively) without jeopardizing the low-dose lung volume (V5). H-RA plans gave the lowest mean maximum spinal cord dose (34.4 Gy, 3.9 Gy < CRT and 2.2 Gy < RA plans) and NTCP of lung. Higher average MU per fraction (addition 52.4 MU) was observed with a reduced treatment time compared with CRT plans. Conclusion: The H-RA technique was superior in dosimetric outcomes for treating locally-advanced NSCLC compared to CRT and RA.

  2. A study of the dynamics of a discrete auroral arc

    International Nuclear Information System (INIS)

    Marklund, G.; Sandahl, I.; Opgenoorth, H.

    1981-06-01

    High resolution electric field and particle data, obtained by the S23L1 rocket crossing over a discrete prebreakup arc in January 1979, are studied in coordination with ground observations in order to clarify the electrodynamics of the arc and its surroundings. Height-integrated conductivities have been calculated from the particle data, including the ionization effect of precipitating protons, and assuming a steady state balance between ion production and recombination losses. High resolution optical information of arc location relative to the rocket permitted a check of the validity of this assumption for each fluxtube passed by the rocket. Another check was provided by a comparison between calculated and observed electron densities along the rocket trajectory. (author)

  3. Setup accuracy of stereoscopic X-ray positioning with automated correction for rotational errors in patients treated with conformal arc radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Soete, Guy; Verellen, Dirk; Tournel, Koen; Storme, Guy

    2006-01-01

    We evaluated setup accuracy of NovalisBody stereoscopic X-ray positioning with automated correction for rotational errors with the Robotics Tilt Module in patients treated with conformal arc radiotherapy for prostate cancer. The correction of rotational errors was shown to reduce random and systematic errors in all directions. (NovalisBody TM and Robotics Tilt Module TM are products of BrainLAB A.G., Heimstetten, Germany)

  4. 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.

  5. 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...

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

    International Nuclear Information System (INIS)

    Foroudi, Farshad; Kron, Tomas; Wilson, Lesley; Bressel, Mathias; Haworth, Annette; Hornby, Colin; Pham, Daniel; Cramb, Jim; Gill, Suki; Tai, Keen Hun

    2012-01-01

    To compare 3 Dimensional Conformal radiotherapy (3D-CRT) with Intensity Modulated Radiotherapy (IMRT) with Volumetric-Modulated Arc Therapy (VMAT) for bladder cancer. 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. 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 < 0.05). Average treatment delivery time were 2:25min (range 2:01–3:09) for 3D-CRT; 4:39 (range 3:41–6:40) for IMRT; and 1:14 (range 1:13–1:14) for VMAT. In selected patients, the SIB did not result in a higher dose to small bowel or rectum. 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

  7. Dynamic neutron scattering from conformational dynamics. I. Theory and Markov models.

    Science.gov (United States)

    Lindner, Benjamin; Yi, Zheng; Prinz, Jan-Hendrik; Smith, Jeremy C; Noé, Frank

    2013-11-07

    The dynamics of complex molecules can be directly probed by inelastic neutron scattering experiments. However, many of the underlying dynamical processes may exist on similar timescales, which makes it difficult to assign processes seen experimentally to specific structural rearrangements. Here, we show how Markov models can be used to connect structural changes observed in molecular dynamics simulation directly to the relaxation processes probed by scattering experiments. For this, a conformational dynamics theory of dynamical neutron and X-ray scattering is developed, following our previous approach for computing dynamical fingerprints of time-correlation functions [F. Noé, S. Doose, I. Daidone, M. Löllmann, J. Chodera, M. Sauer, and J. Smith, Proc. Natl. Acad. Sci. U.S.A. 108, 4822 (2011)]. Markov modeling is used to approximate the relaxation processes and timescales of the molecule via the eigenvectors and eigenvalues of a transition matrix between conformational substates. This procedure allows the establishment of a complete set of exponential decay functions and a full decomposition into the individual contributions, i.e., the contribution of every atom and dynamical process to each experimental relaxation process.

  8. ARC Operations

    Science.gov (United States)

    coordination on a regular basis. The overall ARC organizational structure is shown below. Organizational Structure Dynamics and Control of Vehicles Human Centered Modeling and Simulation High Performance

  9. X-ray-assisted positioning of patients treated by conformal arc radiotherapy for prostate cancer: Comparison of setup accuracy using implanted markers versus bony structures

    International Nuclear Information System (INIS)

    Soete, Guy; Cock, Mieke de; Verellen, Dirk; Michielsen, Dirk; Keuppens, Frans; Storme, Guy

    2007-01-01

    Purpose: The aim of this study was to compare setup accuracy of NovalisBody stereoscopic X-ray positioning using implanted markers in the prostate vs. bony structures in patients treated with dynamic conformal arc radiotherapy for prostate cancer. Methods and Materials: Random and systematic setup errors (RE and SE) of the isocenter with regard to the center of gravity of three fiducial markers were measured by means of orthogonal verification films in 120 treatment sessions in 12 patients. Positioning was performed using NovalisBody semiautomated marker fusion. The results were compared with a control group of 261 measurements in 15 patients who were positioned with NovalisBody automated bone fusion. In addition, interfraction and intrafraction prostate motion was registered in the patients with implanted markers. Results: Marker-based X-ray positioning resulted in a reduction of RE as well as SE in the anteroposterior, craniocaudal, and left-right directions compared with those in the control group. The interfraction prostate displacements with regard to the bony pelvis that could be avoided by marker positioning ranged between 1.6 and 2.8 mm for RE and between 1.3 and 4.3 mm for SE. Intrafraction random and systematic prostate movements ranged between 1.4 and 2.4 mm and between 0.8 and 1.3 mm, respectively. Conclusion: The problem of interfraction prostate motion can be solved by using implanted markers. In addition, the NovalisBody X-ray system performs more accurately with markers compared with bone fusion. Intrafraction organ motion has become the limiting factor for margin reduction around the clinical target volume

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

    International Nuclear Information System (INIS)

    Fidanzio, Andrea; Mameli, Alessandra; Placidi, Elisa; Greco, Francesca; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D'Angelillo, Rolando; Cellini, Francesco; Trodella, Lucio; Cilla, Savino; Grimaldi, Luca; D'Onofrio, Guido; Azario, Luigi; Piermattei, Angelo

    2008-01-01

    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 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 t and the dose at half thickness, D 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 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 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 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

  11. Characterization of conformational dynamics of bistable RNA by equilibrium and non-equilibrium NMR.

    Science.gov (United States)

    Fürtig, Boris; Reining, Anke; Sochor, Florian; Oberhauser, Eva Marie; Heckel, Alexander; Schwalbe, Harald

    2014-12-19

    Unlike proteins, a given RNA sequence can adopt more than a single conformation. The two (or more) conformations are long-lived and have similar stabilities, but interconvert only slowly. Such bi- or multistability is often linked to the biological functions of the RNA. This unit describes how nuclear magnetic resonance (NMR) spectroscopy can be used to characterize the conformational dynamics of bistable RNAs. Copyright © 2014 John Wiley & Sons, Inc.

  12. Arc root dynamics in high power plasma torches – Evidence of ...

    Indian Academy of Sciences (India)

    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 ...

  13. Exotic Galilean conformal symmetry and its dynamical realisations

    International Nuclear Information System (INIS)

    Lukierski, J.; Stichel, P.C.; Zakrzewski, W.J.

    2006-01-01

    The six-dimensional exotic Galilean algebra in (2+1) dimensions with two central charges m and θ, is extended when m=0, to a ten-dimensional Galilean conformal algebra with dilatation, expansion, two acceleration generators and the central charge θ. A realisation of such a symmetry is provided by a model with higher derivatives recently discussed in [P.C. Stichel, W.J. Zakrzewski, Ann. Phys. 310 (2004) 158]. We consider also a realisation of the Galilean conformal symmetry for the motion with a Coulomb potential and a magnetic vortex interaction. Finally, we study the restriction, as well as the modification, of the Galilean conformal algebra obtained after the introduction of the minimally coupled constant electric and magnetic fields

  14. Langevin dynamics of conformational transformations induced by the charge-curvature interaction

    DEFF Research Database (Denmark)

    Gaididei, Yuri Borisovich; Gorria, C.; Christiansen, Peter Leth

    2009-01-01

    The role of thermal fluctuations in the conformational dynamics of a single closed filament is studied. It is shown that, due to the interaction between charges and bending degrees of freedom, initially circular chains may undergo transformation to polygonal shape.......The role of thermal fluctuations in the conformational dynamics of a single closed filament is studied. It is shown that, due to the interaction between charges and bending degrees of freedom, initially circular chains may undergo transformation to polygonal shape....

  15. Conformational dynamics of ATP/Mg:ATP in motor proteins via data mining and molecular simulation

    Science.gov (United States)

    Bojovschi, A.; Liu, Ming S.; Sadus, Richard J.

    2012-08-01

    The conformational diversity of ATP/Mg:ATP in motor proteins was investigated using molecular dynamics and data mining. Adenosine triphosphate (ATP) conformations were found to be constrained mostly by inter cavity motifs in the motor proteins. It is demonstrated that ATP favors extended conformations in the tight pockets of motor proteins such as F1-ATPase and actin whereas compact structures are favored in motor proteins such as RNA polymerase and DNA helicase. The incorporation of Mg2+ leads to increased flexibility of ATP molecules. The differences in the conformational dynamics of ATP/Mg:ATP in various motor proteins was quantified by the radius of gyration. The relationship between the simulation results and those obtained by data mining of motor proteins available in the protein data bank is analyzed. The data mining analysis of motor proteins supports the conformational diversity of the phosphate group of ATP obtained computationally.

  16. 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

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

    KAUST Repository

    Feng, Yitao; Zhang, Lu; Wu, Shaowen; Liu, Zhijun; Gao, Xin; Zhang, Xu; Liu, Maili; Liu, Jianwei; Huang, Xuhui; Wang, Wenning

    2016-01-01

    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

  18. Monitoring conformational dynamics with solid-state R1ρ experiments

    International Nuclear Information System (INIS)

    Quinn, Caitlin M.; McDermott, Ann E.

    2009-01-01

    A new application of solid-state rotating frame (R 1ρ ) relaxation experiments to observe conformational dynamics is presented. Studies on a model compound, dimethyl sulfone (DMS), show that R 1ρ relaxation due to reorientation of a chemical shift anisotropy (CSA) tensor undergoing chemical exchange can be used to monitor slow-to-intermediate timescale conformational exchange processes. Control experiments used d 6 -DMS and alanine to confirm that the technique is monitoring reorientation of the CSA tensor rather than dipolar interactions or methyl group rotation. The application of this method to proteins could represent a new site-specific probe of conformational dynamics

  19. Revealing time bunching effect in single-molecule enzyme conformational dynamics.

    Science.gov (United States)

    Lu, H Peter

    2011-04-21

    In this perspective, we focus our discussion on how the single-molecule spectroscopy and statistical analysis are able to reveal enzyme hidden properties, taking the study of T4 lysozyme as an example. Protein conformational fluctuations and dynamics play a crucial role in biomolecular functions, such as in enzymatic reactions. Single-molecule spectroscopy is a powerful approach to analyze protein conformational dynamics under physiological conditions, providing dynamic perspectives on a molecular-level understanding of protein structure-function mechanisms. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of a polysaccharide of E. coli B cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor-acceptor probe pair tethered to T4 lysozyme domains involving open-close hinge-bending motions. Based on the single-molecule spectroscopic results, molecular dynamics simulation, a random walk model analysis, and a novel 2D statistical correlation analysis, we have revealed a time bunching effect in protein conformational motion dynamics that is critical to enzymatic functions. Bunching effect implies that conformational motion times tend to bunch in a finite and narrow time window. We show that convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. Evidently, the bunching effect is likely common in protein conformational dynamics involving in conformation-gated protein functions. In this perspective, we will also discuss a new approach of 2D regional correlation analysis capable of analyzing fluctuation dynamics of complex multiple correlated and anti-correlated fluctuations under a non-correlated noise background. Using this new method, we are able to map out any defined segments along the fluctuation trajectories and determine whether they are correlated, anti-correlated, or non-correlated; after which, a

  20. 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

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

    Science.gov (United States)

    2011-01-01

    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 conformational ensembles from

  2. Global Brain Dynamics During Social Exclusion Predict Subsequent Behavioral Conformity

    OpenAIRE

    Wasylyshyn, Nick; Hemenway, Brett; Garcia, Javier O.; Cascio, Christopher N.; O'Donnell, Matthew Brook; Bingham, C. Raymond; Simons-Morton, Bruce; Vettel, Jean M.; Falk, Emily B.

    2017-01-01

    Individuals react differently to social experiences; for example, people who are more sensitive to negative social experiences, such as being excluded, may be more likely to adapt their behavior to fit in with others. We examined whether functional brain connectivity during social exclusion in the fMRI scanner can be used to predict subsequent conformity to peer norms. Adolescent males (N = 57) completed a two-part study on teen driving risk: a social exclusion task (Cyberball) during an fMRI...

  3. Conformational Dynamics of Thermus aquaticus DNA Polymerase I during Catalysis

    OpenAIRE

    Xu, Cuiling; Maxwell, Brian A.; Suo, Zucai

    2014-01-01

    Despite the fact that DNA polymerases have been investigated for many years and are commonly used as tools in a number of molecular biology assays, many details of the kinetic mechanism they use to catalyze DNA synthesis remain unclear. Structural and kinetic studies have characterized a rapid, pre-catalytic open-to-close conformational change of the Finger domain during nucleotide binding for many DNA polymerases including Thermus aquaticus DNA polymerase I (Taq Pol), a thermostable enzyme c...

  4. Radiotherapy for Adult Medulloblastoma: Evaluation of Helical Tomotherapy, Volumetric Intensity Modulated Arc Therapy, and Three-Dimensional Conformal Radiotherapy and the Results of Helical Tomotherapy Therapy

    Directory of Open Access Journals (Sweden)

    Sun Zong-wen

    2018-01-01

    Full Text Available Introduction. All adult medulloblastoma (AMB patients should be treated with craniospinal irradiation (CSI postoperatively. Because of the long irradiation range, multiple radiation fields must be designed for conventional radiotherapy technology. CSI can be completed in only one session with helical tomotherapy (HT. We evaluated the dose of HT, volumetric intensity modulated arc therapy (VMAT, and three-dimensional conformal radiotherapy (3D-CRT of AMB and the results of 5 cases of AMB treated with HT. Methods. Complete craniospinal and posterior cranial fossa irradiation with HT, VMAT, and 3D-CRT and dose evaluation were performed. And results of 5 cases of AMB treated with HT were evaluated. Results. A large volume of tissue was exposed to low dose radiation in the organs at risk (OAR, while a small volume was exposed to high dose radiation with HT. The conformity and uniformity of the targets were good with HT and VMAT, and the volume of targets exposed to high dose with VMAT was larger than that of HT. The uniformity of 3D-CRT was also good, but the dose conformity was poor. The main toxicity was hematologic toxicity, without 4th-degree bone marrow suppression. There was 3rd-degree inhibition in the white blood cells, hemoglobin, and platelets. The three female patients suffered menstrual disorders during the course of radiation. Two female patients with heavy menstruation suffered 3rd-degree anemia inhibition, and 2 patients suffered amenorrhea after radiotherapy. Although menstrual cycle was normal, the third patient was not pregnant. Conclusion. CSI with HT is convenient for clinical practice, and the side effects are mild. With good conformity and uniformity, VMAT can also be used for selection in CSI. For poor conformity, 3D-CRT should not be the priority selection for CSI. In female patients, the ovaries should be protected.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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.

  6. Bladder radiotherapy treatment: A retrospective comparison of 3-dimensional conformal radiotherapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy plans

    Energy Technology Data Exchange (ETDEWEB)

    Pasciuti, Katia, E-mail: k.pasciuti@virgilio.it [Department of Radiotherapy Physics, Royal Free Hospital, London (United Kingdom); Kuthpady, Shrinivas [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom); Anderson, Anne; Best, Bronagh [Department of Radiotherapy Physics, Royal Free Hospital, London (United Kingdom); Waqar, Saleem; Chowdhury, Subhra [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom)

    2017-04-01

    To examine tumor's and organ's response when different radiotherapy plan techniques are used. Ten patients with confirmed bladder tumors were first treated using 3-dimensional conformal radiotherapy (3DCRT) and subsequently the original plans were re-optimized using the intensity-modulated radiation treatment (IMRT) and volumetric-modulated arc therapy (VMAT)-techniques. Targets coverage in terms of conformity and homogeneity index, TCP, and organs' dose limits, including integral dose analysis were evaluated. In addition, MUs and treatment delivery times were compared. Better minimum target coverage (1.3%) was observed in VMAT plans when compared to 3DCRT and IMRT ones confirmed by a statistically significant conformity index (CI) results. Large differences were observed among techniques in integral dose results of the femoral heads. Even if no statistically significant differences were reported in rectum and tissue, a large amount of energy deposition was observed in 3DCRT plans. In any case, VMAT plans provided better organs and tissue sparing confirmed also by the normal tissue complication probability (NTCP) analysis as well as a better tumor control probability (TCP) result. Our analysis showed better overall results in planning using VMAT techniques. Furthermore, a total time reduction in treatment observed among techniques including gantry and collimator rotation could encourage using the more recent one, reducing target movements and patient discomfort.

  7. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    Science.gov (United States)

    Duan, Zhao-Wen; Li, Wei; Xie, Ping; Dou, Shuo-Xing; Wang, Peng-Ye

    2010-04-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking" interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon.

  8. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    International Nuclear Information System (INIS)

    Zhao-Wen, Duan; Wei, Li; Ping, Xie; Shuo-Xing, Dou; Peng-Ye, Wang

    2010-01-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking” interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon. (cross-disciplinary physics and related areas of science and technology)

  9. Conformal Field Theory as Microscopic Dynamics of Incompressible Euler and Navier-Stokes Equations

    International Nuclear Information System (INIS)

    Fouxon, Itzhak; Oz, Yaron

    2008-01-01

    We consider the hydrodynamics of relativistic conformal field theories at finite temperature. We show that the limit of slow motions of the ideal hydrodynamics leads to the nonrelativistic incompressible Euler equation. For viscous hydrodynamics we show that the limit of slow motions leads to the nonrelativistic incompressible Navier-Stokes equation. We explain the physical reasons for the reduction and discuss the implications. We propose that conformal field theories provide a fundamental microscopic viewpoint of the equations and the dynamics governed by them

  10. Conformal field theory as microscopic dynamics of incompressible Euler and Navier-Stokes equations.

    Science.gov (United States)

    Fouxon, Itzhak; Oz, Yaron

    2008-12-31

    We consider the hydrodynamics of relativistic conformal field theories at finite temperature. We show that the limit of slow motions of the ideal hydrodynamics leads to the nonrelativistic incompressible Euler equation. For viscous hydrodynamics we show that the limit of slow motions leads to the nonrelativistic incompressible Navier-Stokes equation. We explain the physical reasons for the reduction and discuss the implications. We propose that conformal field theories provide a fundamental microscopic viewpoint of the equations and the dynamics governed by them.

  11. 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.)

  12. Molecular dynamics of conformation-specific dopamine transporter-inhibitor complexes.

    Science.gov (United States)

    Jean, Bernandie; Surratt, Christopher K; Madura, Jeffry D

    2017-09-01

    The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation. The 3β-aryltropane cocaine analogs LX10 and LX11, however, differ only in stereochemistry and share a preference for the outward-facing DAT, yet are reported to vary widely in abuse potential in an animal model. In search of the molecular basis for DAT conformation preference, complexes of cocaine, benztropine, LX10 or LX11 bound to each DAT conformation were subjected to 100ns of all-atom molecular dynamics simulation. Results were consistent with previous findings from cysteine accessibility assays used to assess an inhibitor's DAT conformation preference. The respective 2β- and 2α-substituted phenyltropanes of LX10 and LX11 interacted with hydrophobic regions of the DAT S1 binding site that were inaccessible to cocaine. Solvent accessibility measurements also revealed subtle differences in inhibitor positioning within a given DAT conformation. This work serves to advance our understanding of the conformational selectivity of DAT inhibitors and suggests that MD may be useful in antipsychostimulant therapeutic design. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

    International Nuclear Information System (INIS)

    Wang, Xin; Li, Guangjun; Zhang, Yingjie; Bai, Sen; Xu, Feng; Wei, Yuquan; Gong, Youling

    2013-01-01

    To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V 20/30 , and mean dose of the left kidney, as well as the V 20/30 of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V 20 of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future

  14. 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.

  15. 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.

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

    DEFF Research Database (Denmark)

    Nuermaimaiti, Ajiguli

    2013-01-01

    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...

  17. Conformal symmetry and non-relativistic second-order fluid dynamics

    International Nuclear Information System (INIS)

    Chao Jingyi; Schäfer, Thomas

    2012-01-01

    We study the constraints imposed by conformal symmetry on the equations of fluid dynamics at second order in the gradients of the hydrodynamic variables. At zeroth order, conformal symmetry implies a constraint on the equation of state, E 0 =2/3 P, where E 0 is the energy density and P is the pressure. At first order, conformal symmetry implies that the bulk viscosity must vanish. We show that at second order, conformal invariance requires that two-derivative terms in the stress tensor must be traceless, and that it determines the relaxation of dissipative stresses to the Navier–Stokes form. We verify these results by solving the Boltzmann equation at second order in the gradient expansion. We find that only a subset of the terms allowed by conformal symmetry appear. - Highlights: ► We derive conformal constraints for the stress tensor of a scale invariant fluid. ► We determine the relaxation time in kinetic theory. ► We compute the rate of entropy production in second-order fluid dynamics.

  18. Dynamic intensity-modulated non-coplanar arc radiotherapy (INCA) for head and neck cancer

    International Nuclear Information System (INIS)

    Krayenbuehl, Jerome; Davis, J. Bernard; Ciernik, I. Frank

    2006-01-01

    Background and purpose: To define the potential advantages of intensity-modulated radiotherapy (IMRT) applied using a non-coplanar dynamic arc technique for the treatment of head and neck cancer. Materials and methods: External beam radiotherapy (EBRT) was planned in ten patients with head and neck cancer using coplanar IMRT and non-coplanar arc techniques, termed intensity modulated non-coplanar arc EBRT (INCA). Planning target volumes (PTV1) of first order covered the gross tumor volume and surrounding clinical target volume treated with 68-70 Gy, whereas PTV2 covered the elective lymph nodes with 54-55 Gy using a simultaneous internal boost. Treatment plan comparison between IMRT and INCA was carried out using dose-volume histogram and 'equivalent uniform dose' (EUD). Results: INCA resulted in better dose coverage and homogeneity of the PTV1, PTV2, and reduced dose delivered to most of the organs at risk (OAR). For the parotid glands, a reduction of the mean dose of 2.9 (±2.0) Gy was observed (p 0.002), the mean dose to the larynx was reduced by 6.9 (±2.9) Gy (p 0.003), the oral mucosa by 2.4 (±1.1) Gy (p < 0.001), and the maximal dose to the spinal cord by 3.2 (±1.7) Gy (p = 0.004). The mean dose to the brain was increased by 3.0 (±1.4) Gy (p = 0.002) and the mean lung dose increased by 0.2 (±0.4) Gy (p = 0.87). The EUD suggested better avoidance of the OAR, except for the lung, and better coverage and dose uniformity were achieved with INCA compared to IMRT. Conclusion: Dose delivery accuracy with IMRT using a non-coplanar dynamic arc beam geometry potentially improves treatment of head and neck cancer

  19. Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

    Science.gov (United States)

    Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

    2016-08-01

    Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

  20. Binding mechanism and dynamic conformational change of C subunit of PKA with different pathways.

    Science.gov (United States)

    Chu, Wen-Ting; Chu, Xiakun; Wang, Jin

    2017-09-19

    The catalytic subunit of PKA (PKAc) exhibits three major conformational states (open, intermediate, and closed) during the biocatalysis process. Both ATP and substrate/inhibitor can effectively induce the conformational changes of PKAc from open to closed states. Aiming to explore the mechanism of this allosteric regulation, we developed a coarse-grained model and analyzed the dynamics of conformational changes of PKAc during binding by performing molecular dynamics simulations for apo PKAc, binary PKAc (PKAc with ATP, PKAc with PKI), and ternary PKAc (PKAc with ATP and PKI). Our results suggest a mixed binding mechanism of induced fit and conformational selection, with the induced fit dominant. The ligands can drive the movements of Gly-rich loop as well as some regions distal to the active site in PKAc and stabilize them at complex state. In addition, there are two parallel pathways (pathway with PKAc-ATP as an intermediate and pathway PKAc-PKI as an intermediate) during the transition from open to closed states. By molecular dynamics simulations and rate constant analyses, we find that the pathway through PKAc-ATP intermediate is the main binding route from open to closed state because of the fact that the bound PKI will hamper ATP from successful binding and significantly increase the barrier for the second binding subprocess. These findings will provide fundamental insights of the mechanisms of PKAc conformational change upon binding.

  1. Role of conformational dynamics in kinetics of an enzymatic cycle in a nonequilibrium steady state

    Science.gov (United States)

    Min, Wei; Xie, X. Sunney; Bagchi, Biman

    2009-08-01

    Enzyme is a dynamic entity with diverse time scales, ranging from picoseconds to seconds or even longer. Here we develop a rate theory for enzyme catalysis that includes conformational dynamics as cycling on a two-dimensional (2D) reaction free energy surface involving an intrinsic reaction coordinate (X) and an enzyme conformational coordinate (Q). The validity of Michaelis-Menten (MM) equation, i.e., substrate concentration dependence of enzymatic velocity, is examined under a nonequilibrium steady state. Under certain conditions, the classic MM equation holds but with generalized microscopic interpretations of kinetic parameters. However, under other conditions, our rate theory predicts either positive (sigmoidal-like) or negative (biphasic-like) kinetic cooperativity due to the modified effective 2D reaction pathway on X-Q surface, which can explain non-MM dependence previously observed on many monomeric enzymes that involve slow or hysteretic conformational transitions. Furthermore, we find that a slow conformational relaxation during product release could retain the enzyme in a favorable configuration, such that enzymatic turnover is dynamically accelerated at high substrate concentrations. The effect of such conformation retainment in a nonequilibrium steady state is evaluated.

  2. 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 p...

  3. Reducing scan angle using adaptive prior knowledge for a limited-angle intrafraction verification (LIVE) system for conformal arc radiotherapy

    Science.gov (United States)

    Zhang, Yawei; Yin, Fang-Fang; Zhang, You; Ren, Lei

    2017-05-01

    The purpose of this study is to develop an adaptive prior knowledge guided image estimation technique to reduce the scan angle needed in the limited-angle intrafraction verification (LIVE) system for 4D-CBCT reconstruction. The LIVE system has been previously developed to reconstruct 4D volumetric images on-the-fly during arc treatment for intrafraction target verification and dose calculation. In this study, we developed an adaptive constrained free-form deformation reconstruction technique in LIVE to further reduce the scanning angle needed to reconstruct the 4D-CBCT images for faster intrafraction verification. This technique uses free form deformation with energy minimization to deform prior images to estimate 4D-CBCT based on kV-MV projections acquired in extremely limited angle (orthogonal 3°) during the treatment. Note that the prior images are adaptively updated using the latest CBCT images reconstructed by LIVE during treatment to utilize the continuity of the respiratory motion. The 4D digital extended-cardiac-torso (XCAT) phantom and a CIRS 008A dynamic thoracic phantom were used to evaluate the effectiveness of this technique. The reconstruction accuracy of the technique was evaluated by calculating both the center-of-mass-shift (COMS) and 3D volume-percentage-difference (VPD) of the tumor in reconstructed images and the true on-board images. The performance of the technique was also assessed with varied breathing signals against scanning angle, lesion size, lesion location, projection sampling interval, and scanning direction. In the XCAT study, using orthogonal-view of 3° kV and portal MV projections, this technique achieved an average tumor COMS/VPD of 0.4  ±  0.1 mm/5.5  ±  2.2%, 0.6  ±  0.3 mm/7.2  ±  2.8%, 0.5  ±  0.2 mm/7.1  ±  2.6%, 0.6  ±  0.2 mm/8.3  ±  2.4%, for baseline drift, amplitude variation, phase shift, and patient breathing signal variation

  4. Dynamics of organizational culture: Individual beliefs vs. social conformity

    OpenAIRE

    Ellinas, Christos; Allan, Neil; Johansson, Anders

    2017-01-01

    The complex nature of organizational culture challenges our ability to infers its underlying dynamics from observational studies. Recent computational studies have adopted a distinct different view, where plausible mechanisms are proposed to describe a wide range of social phenomena, including the onset and evolution of organizational culture. In this spirit, this work introduces an empirically-grounded, agent-based model which relaxes a set of assumptions that describes past work - (a) omitt...

  5. Chest wall desmoid tumours treated with definitive radiotherapy: a plan comparison of 3D conformal radiotherapy, intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy

    International Nuclear Information System (INIS)

    Liu, Jia; Ng, Diana; Lee, James; Stalley, Paul; Hong, Angela

    2016-01-01

    Definitive radiotherapy is often used for chest wall desmoid tumours due to size or anatomical location. The delivery of radiotherapy is challenging due to the large size and constraints of normal surrounding structures. We compared the dosimetry of 3D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) to evaluate the best treatment option. Ten consecutive patients with inoperable chest wall desmoid tumours (PTV range 416–4549 cm 3 ) were selected. For each patient, 3DCRT, IMRT and VMAT plans were generated and the Conformity Index (CI), organ at risk (OAR) doses and monitor unit (MU) were evaluated. The Wilcoxon signed-rank test was used to compare dose delivered to both target and OARs. The mean number of fields for 3DCRT and IMRT were 6.3 ± 2.1, 7.2 ± 1.8. The mean number of arcs for VMAT was 3.7 ± 1.1. The mean conformity index of VMAT (0.98 ± 0.14) was similar to that of IMRT (1.03 ± 0.13), both of which were significantly better than 3DCRT (1.35 ± 0.20; p = 0.005). The mean dose to lung was significantly higher for 3DCRT (11.9Gy ± 7.9) compared to IMRT (9.4Gy ± 5.4, p = 0.014) and VMAT (8.9Gy ± 4.5, p = 0.017). For the 3 females, the low dose regions in the ipsilateral breast for VMAT were generally less with VMAT. IMRT plans required 1427 ± 532 MU per fraction which was almost 4-fold higher than 3DCRT (313 ± 112, P = 0.005). Compared to IMRT, VMAT plans required 60 % less MU (570 ± 285, P = 0.005). For inoperable chest wall desmoid tumours, VMAT delivered equivalent target coverage when compared to IMRT but required 60 % less MU. Both VMAT and IMRT were superior to 3DCRT in terms of better PTV coverage and sparing of lung tissue

  6. Dynamic neutron scattering from conformational dynamics. II. Application using molecular dynamics simulation and Markov modeling.

    Science.gov (United States)

    Yi, Zheng; Lindner, Benjamin; Prinz, Jan-Hendrik; Noé, Frank; Smith, Jeremy C

    2013-11-07

    Neutron scattering experiments directly probe the dynamics of complex molecules on the sub pico- to microsecond time scales. However, the assignment of the relaxations seen experimentally to specific structural rearrangements is difficult, since many of the underlying dynamical processes may exist on similar timescales. In an accompanying article, we present a theoretical approach to the analysis of molecular dynamics simulations with a Markov State Model (MSM) that permits the direct identification of structural transitions leading to each contributing relaxation process. Here, we demonstrate the use of the method by applying it to the configurational dynamics of the well-characterized alanine dipeptide. A practical procedure for deriving the MSM from an MD is introduced. The result is a 9-state MSM in the space of the backbone dihedral angles and the side-chain methyl group. The agreement between the quasielastic spectrum calculated directly from the atomic trajectories and that derived from the Markov state model is excellent. The dependence on the wavevector of the individual Markov processes is described. The procedure means that it is now practicable to interpret quasielastic scattering spectra in terms of well-defined intramolecular transitions with minimal a priori assumptions as to the nature of the dynamics taking place.

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Asadinezhad, Ahmad, E-mail: asadinezhad@cc.iut.ac.ir; Kelich, Payam

    2017-01-15

    Highlights: • Poly (trimethylene terephthalate) (PTT) conformation adopts a folded shape near nanofiller surface. • Graphene and carbon nanotube with different size and chemistry were simulated. • Graphene functionalization induces stronger confinement on PTT chain conformation. • PTT chain motion alters in dynamics mode as it becomes adsorbed onto nanofillers. • PTT reveals further changes near graphene than carbon nanotube surface. - Abstract: 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.

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

    International Nuclear Information System (INIS)

    Asadinezhad, Ahmad; Kelich, Payam

    2017-01-01

    Highlights: • Poly (trimethylene terephthalate) (PTT) conformation adopts a folded shape near nanofiller surface. • Graphene and carbon nanotube with different size and chemistry were simulated. • Graphene functionalization induces stronger confinement on PTT chain conformation. • PTT chain motion alters in dynamics mode as it becomes adsorbed onto nanofillers. • PTT reveals further changes near graphene than carbon nanotube surface. - Abstract: 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.

  10. 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.

  11. Conformational dynamics of semiflexibly bridged electron donor-acceptor systems comprising long aliphatic tails

    NARCIS (Netherlands)

    Bleisteiner, B.; Marian, T.; Schneider, S.; Brouwer, A.M.; Verhoeven, J.W.

    2001-01-01

    In continuation of our previous work on the conformational dynamics (harpooning mechanism) of semiflexibly bridged electron donor-acceptor systems we have studied a derivative with two long aliphatic chains tethered to the donor and acceptor moieties, respectively. The fitting of the time- and

  12. Numerical simulation for arc-plasma dynamics during contact opening process in electrical circuit-breakers

    International Nuclear Information System (INIS)

    Gupta, D N; Srinivas, D; Patil, G N; Kale, S S; Potnis, S B

    2010-01-01

    The high-energy, high-current thermal plasma that develops between electric contacts in a gas circuit-breaker during circuit interruption is an important phenomenon in the power transmission industry. The high temperature and pressure arc dissipates the tremendous amount of energy generated by the fault current. Simultaneously, this energy has to be transferred away from the contacts to build the dielectric strength level of the circuit-breaker. In order to interrupt the current, the arc must be weakened and finally extinguished. We model these phenomena by using a computer software code based on the solution of the unsteady Euler equations of gas dynamics. We consider the equations of fluid flows. These equations are solved numerically in complex circuit breaker geometries using a finite-volume method. The domain is initially filled with SF 6 gas. We begin our simulations from cold mode, where the fault current is not present (hence no arc). An axis-symmetric geometry of a 145 kV gas circuit-breaker is considered to study the pressure, density, and temperature profile during contact opening process.

  13. Modulation of the Conformational Dynamics of Apo-Adenylate Kinase through a π-Cation Interaction.

    Science.gov (United States)

    Halder, Ritaban; Manna, Rabindra Nath; Chakraborty, Sandipan; Jana, Biman

    2017-06-15

    Large-scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in a way that closely resembles an open-to-closed conformational transition. Here, equilibrium simulations, free-energy simulations, and quantum mechanics/molecular mechanics (QM/MM) calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. In addition to its conventional open state, Escherichia coli apo-ADK adopts conformations that resemble a closed-like intermediate, the "half-open-half-closed" (HOHC) state, and a π-cation interaction can account for the stability of this HOHC state. Energetics and the electronic properties of this π-cation interaction have been explored using QM/MM calculations. Upon rescinding the π-cation interaction, the conformational landscape of the apo-ADK changes completely. The apo-ADK population is shifted completely toward the open state. This π-cation interaction is highly conserved in bacterial ADK; the cationic guanidinium moiety of a conserved ARG interacts with the delocalized π-electron cloud of either PHE or TYR. Interestingly, this study demonstrates the modulation of a principal protein dynamics by a conserved specific π-cation interaction across different organisms.

  14. Hierarchical Conformational Analysis of Native Lysozyme Based on Sub-Millisecond Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    Full Text Available Hierarchical organization of free energy landscape (FEL for native globular proteins has been widely accepted by the biophysics community. However, FEL of native proteins is usually projected onto one or a few dimensions. Here we generated collectively 0.2 milli-second molecular dynamics simulation trajectories in explicit solvent for hen egg white lysozyme (HEWL, and carried out detailed conformational analysis based on backbone torsional degrees of freedom (DOF. Our results demonstrated that at micro-second and coarser temporal resolutions, FEL of HEWL exhibits hub-like topology with crystal structures occupying the dominant structural ensemble that serves as the hub of conformational transitions. However, at 100 ns and finer temporal resolutions, conformational substates of HEWL exhibit network-like topology, crystal structures are associated with kinetic traps that are important but not dominant ensembles. Backbone torsional state transitions on time scales ranging from nanoseconds to beyond microseconds were found to be associated with various types of molecular interactions. Even at nanoseconds temporal resolution, the number of conformational substates that are of statistical significance is quite limited. These observations suggest that detailed analysis of conformational substates at multiple temporal resolutions is both important and feasible. Transition state ensembles among various conformational substates at microsecond temporal resolution were observed to be considerably disordered. Life times of these transition state ensembles are found to be nearly independent of the time scales of the participating torsional DOFs.

  15. 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.

  16. Intensity-modulated arc therapy simplified

    International Nuclear Information System (INIS)

    Wong, Eugene; Chen, Jeff Z.; Greenland, Jonathan

    2002-01-01

    Purpose: We present a treatment planning strategy for intensity-modulated radiation therapy using gantry arcs with dynamic multileaf collimator, previously termed intensity-modulated arc therapy (IMAT). Methods and Materials: The planning strategy is an extension of the photon bar arc and asymmetric arc techniques and is classified into three levels of complexity, with increasing number of gantry arcs. This principle allows us to generalize the analysis of the number of arcs required for intensity modulation for a given treatment site. Using a phantom, we illustrate how the current technique is more flexible than the photon bar arc technique. We then compare plans from our strategy with conventional three-dimensional conformal treatment plans for three sites: prostate (prostate plus seminal vesicles), posterior pharyngeal wall, and chest wall. Results: Our strategy generates superior IMAT treatment plans compared to conventional three-dimensional conformal plans. The IMAT plans spare critical organs well, and the trade-off for simplicity is that the dose uniformity in the target volume may not rival that of true inverse treatment plans. Conclusions: The analyses presented in this paper give a better understanding of IMAT plans. Our strategy is easier to understand and more efficient in generating plans than inverse planning systems; our plans are also simpler to modify, and quality assurance is more intuitive

  17. Single Molecule Cluster Analysis Identifies Signature Dynamic Conformations along the Splicing Pathway

    Science.gov (United States)

    Blanco, Mario R.; Martin, Joshua S.; Kahlscheuer, Matthew L.; Krishnan, Ramya; Abelson, John; Laederach, Alain; Walter, Nils G.

    2016-01-01

    The spliceosome is the dynamic RNA-protein machine responsible for faithfully splicing introns from precursor messenger RNAs (pre-mRNAs). Many of the dynamic processes required for the proper assembly, catalytic activation, and disassembly of the spliceosome as it acts on its pre-mRNA substrate remain poorly understood, a challenge that persists for many biomolecular machines. Here, we developed a fluorescence-based Single Molecule Cluster Analysis (SiMCAn) tool to dissect the manifold conformational dynamics of a pre-mRNA through the splicing cycle. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified a conformation adopted late in splicing by a 3′ splice site mutant, invoking a mechanism for substrate proofreading. SiMCAn presents a novel framework for interpreting complex single molecule behaviors that should prove widely useful for the comprehensive analysis of a plethora of dynamic cellular machines. PMID:26414013

  18. 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.

  19. 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.

  20. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

    International Nuclear Information System (INIS)

    Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian; Roitberg, Adrian E.

    2015-01-01

    The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data

  1. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

    Energy Technology Data Exchange (ETDEWEB)

    Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian, E-mail: sfalberti@gmail.com [Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal (Argentina); Roitberg, Adrian E. [Departments of Physics and Chemistry, University of Florida, Gainesville, Florida 32611 (United States)

    2015-06-28

    The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

  2. Covalent dye attachment influences the dynamics and conformational properties of flexible peptides.

    Directory of Open Access Journals (Sweden)

    Manuel P Luitz

    Full Text Available Fluorescence spectroscopy techniques like Förster resonance energy transfer (FRET and fluorescence correlation spectroscopy (FCS have become important tools for the in vitro and in vivo investigation of conformational dynamics in biomolecules. These methods rely on the distance-dependent quenching of the fluorescence signal of a donor fluorophore either by a fluorescent acceptor fluorophore (FRET or a non-fluorescent quencher, as used in FCS with photoinduced electron transfer (PET. The attachment of fluorophores to the molecule of interest can potentially alter the molecular properties and may affect the relevant conformational states and dynamics especially of flexible biomolecules like intrinsically disordered proteins (IDP. Using the intrinsically disordered S-peptide as a model system, we investigate the impact of terminal fluorescence labeling on the molecular properties. We perform extensive molecular dynamics simulations on the labeled and unlabeled peptide and compare the results with in vitro PET-FCS measurements. Experimental and simulated timescales of end-to-end fluctuations were found in excellent agreement. Comparison between simulations with and without labels reveal that the π-stacking interaction between the fluorophore labels traps the conformation of S-peptide in a single dominant state, while the unlabeled peptide undergoes continuous conformational rearrangements. Furthermore, we find that the open to closed transition rate of S-peptide is decreased by at least one order of magnitude by the fluorophore attachment. Our approach combining experimental and in silico methods provides a benchmark for the simulations and reveals the significant effect that fluorescence labeling can have on the conformational dynamics of small biomolecules, at least for inherently flexible short peptides. The presented protocol is not only useful for comparing PET-FCS experiments with simulation results but provides a strategy to minimize the

  3. The Coupling of Back-arc Extension, Extrusion and Subduction Dynamics in the Eastern Mediterranean

    Science.gov (United States)

    Capitanio, Fabio A.

    2017-04-01

    Extension in the Aegean Sea and lateral Anatolian extrusion are contrasting and seemingly unrelated examples of continental tectonics In the Eastern Mediterranean. It is acknowledged that these must reconcile with the dynamics of Tethys closure and following continental collision along the convergent margin, however the underlying mechanisms have been difficult to pinpoint, thus far. Three-dimensional numerical modelling of the dynamics of subduction and coupling with the mantle and upper plates allows probing the evolution of similar areas, supporting inferences on the ultimate causes for the continental tectonics. I will present models that reproduce the force balance of subducting slabs' buoyancy, mantle flow and upper plate interiors, and emphasise the role of perturbations in the force balance that may have followed slab breakoff, collision and trench land-locking reconstructed during the oceanic closure in the Eastern Mediterranean. These perturbations lead to a range of different margin motions and strain regimes in the upper plate, from rollback and back-arc spreading, to indentation and extrusion along the collisional margin. Different spatial and temporal fingerprints are illustrated for these processes, and while the trench rollback and back-arc spreading are rather stable features, extrusion is transient. When these regimes overlap, rapid and complex rearrangements of the tectonics in the upper plate are the result. The remarkable similarity between the models' and the Eastern Mediterranean tectonic regimes and geophysical observable allows proposing viable driving mechanisms and support inferences on the Miocene-to-Pliocene evolution of this puzzling area.

  4. Dosimetric impact of inter-observer variability for 3D conformal radiotherapy and volumetric modulated arc therapy: the rectal tumor target definition case

    International Nuclear Information System (INIS)

    Lobefalo, Francesca; Cozzi, Luca; Scorsetti, Marta; Mancosu, Pietro; Bignardi, Mario; Reggiori, Giacomo; Tozzi, Angelo; Tomatis, Stefano; Alongi, Filippo; Fogliata, Antonella; Gaudino, Anna; Navarria, Piera

    2013-01-01

    To assess the dosimetric effect induced by inter-observer variability in target definition for 3D-conformal RT (3DCRT) and volumetric modulated arc therapy by RapidArc (RA) techniques for rectal cancer treatment. Ten patients with rectal cancer subjected to neo-adjuvant RT were randomly selected from the internal database. Four radiation oncologists independently contoured the clinical target volume (CTV) in blind mode. Planning target volume (PTV) was defined as CTV + 7 mm in the three directions. Afterwards, shared guidelines between radiation oncologists were introduced to give general criteria for the contouring of rectal target and the four radiation oncologists defined new CTV following the guidelines. For each patient, six intersections (I) and unions (U) volumes were calculated coupling the contours of the various oncologists. This was repeated for the contours drawn after the guidelines. Agreement Index (AI = I/U) was calculated pre and post guidelines. Two RT plans (one with 3DCRT technique using 3–4 fields and one with RA using a single modulated arc) were optimized on each radiation oncologist’s PTV. For each plan the PTV volume receiving at least 95% of the prescribed dose (PTV V95%) was calculated for both target and non-target PTVs. The inter-operator AI pre-guidelines was 0.57 and was increased up to 0.69 post-guidelines. The maximum volume difference between the various CTV couples, drawn for each patient, passed from 380 ± 147 cm 3 to 137 ± 83 cm 3 after the introduction of guidelines. The mean percentage for the non-target PTV V95% was 93.7 ± 9.2% before and 96.6 ± 4.9%after the introduction of guidelines for the 3DCRT, for RA the increase was more relevant, passing from 86.5 ± 13.8% (pre) to 94.5 ± 7.5% (post). The OARs were maximally spared with VMAT technique while the variability between pre and post guidelines was not relevant in both techniques. The contouring inter-observer variability has dosimetric effects in the PTV coverage

  5. Nucleotide-induced conformational dynamics in ABC transporters from structure-based coarse grained modelling.

    Science.gov (United States)

    Flechsig, Holger

    2016-02-01

    ATP-binding cassette (ABC) transporters are integral membrane proteins which mediate the exchange of diverse substrates across membranes powered by ATP molecules. Our understanding of their activity is still hampered since the conformational dynamics underlying the operation of such proteins cannot yet be resolved in detailed molecular dynamics studies. Here a coarse grained model which allows to mimic binding of nucleotides and follow subsequent conformational motions of full-length transporter structures in computer simulations is proposed and implemented. To justify its explanatory quality, the model is first applied to the maltose transporter system for which multiple conformations are known and we find that the model predictions agree remarkably well with the experimental data. For the MalK subunit the switching from open to the closed dimer configuration upon ATP binding is reproduced and, moreover, for the full-length maltose transporter, progression from inward-facing to the outward-facing state is correctly obtained. For the heme transporter HmuUV, for which only the free structure could yet be determined, the model was then applied to predict nucleotide-induced conformational motions. Upon binding of ATP-mimicking ligands the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact, while, at the same time, a pronounced rotation of the transmembrane domains was observed. This finding is supported by normal mode analysis, and, comparison with structural data of the homologous vitamin B12 transporter BtuCD suggests that the observed rotation mechanism may contribute a common functional aspect for this class of ABC transporters. Although in HmuuV noticeable rearrangement of essential transmembrane helices was detected, there are no indications from our simulations that ATP binding alone may facilitate propagation of substrate molecules in this transporter

  6. Global conformational dynamics of a Y-family DNA polymerase during catalysis.

    Directory of Open Access Journals (Sweden)

    Cuiling Xu

    2009-10-01

    Full Text Available Replicative DNA polymerases are stalled by damaged DNA while the newly discovered Y-family DNA polymerases are recruited to rescue these stalled replication forks, thereby enhancing cell survival. The Y-family DNA polymerases, characterized by low fidelity and processivity, are able to bypass different classes of DNA lesions. A variety of kinetic and structural studies have established a minimal reaction pathway common to all DNA polymerases, although the conformational intermediates are not well defined. Furthermore, the identification of the rate-limiting step of nucleotide incorporation catalyzed by any DNA polymerase has been a matter of long debate. By monitoring time-dependent fluorescence resonance energy transfer (FRET signal changes at multiple sites in each domain and DNA during catalysis, we present here a real-time picture of the global conformational transitions of a model Y-family enzyme: DNA polymerase IV (Dpo4 from Sulfolobus solfataricus. Our results provide evidence for a hypothetical DNA translocation event followed by a rapid protein conformational change prior to catalysis and a subsequent slow, post-chemistry protein conformational change. Surprisingly, the DNA translocation step was induced by the binding of a correct nucleotide. Moreover, we have determined the directions, rates, and activation energy barriers of the protein conformational transitions, which indicated that the four domains of Dpo4 moved in a synchronized manner. These results showed conclusively that a pre-chemistry conformational change associated with domain movements was too fast to be the rate-limiting step. Rather, the rearrangement of active site residues limited the rate of correct nucleotide incorporation. Collectively, the conformational dynamics of Dpo4 offer insights into how the inter-domain movements are related to enzymatic function and their concerted interactions with other proteins at the replication fork.

  7. 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...

  8. Probing the conformational dynamics of photosystem I in unconfined and confined spaces.

    Science.gov (United States)

    Das, Gaurav; Chattoraj, Shyamtanu; Nandi, Somen; Mondal, Prasenjit; Saha, Abhijit; Bhattacharyya, Kankan; Ghosh, Surajit

    2017-12-20

    The fluorescence dynamics of Photosystem I (PSI) in bulk water and inside a confined environment like a liposome have been investigated using time resolved confocal microscopy. In bulk water, PSI exhibits a major emission peak at ∼680 nm, while in the liposome it exhibits a markedly blue shifted emission maximum at ∼485 nm. This is indicative of conformational changes due to entrapment and emergence of a stressed conformation of PSI inside the liposome. The observed time constants for the fluorescence lifetime of PSI inside the liposome are significantly high as opposed to PSI in bulk water. More interestingly, the fluorescence intensity of PSI in bulk water exhibits strong fluctuations with many high intensity jumps and these are anti-correlated with the fluorescence lifetime of PSI. In contrast, inside the liposome, no such anti-correlated behaviour is observed. We further demonstrated that PSI exhibits at least two conformational states in bulk water, whereas a single conformation is observed inside the liposome, indicating the conformational rigidity and locking of the PSI complex inside a liposome.

  9. A correspondence between solution-state dynamics of an individual protein and the sequence and conformational diversity of its family.

    Directory of Open Access Journals (Sweden)

    Gregory D Friedland

    2009-05-01

    Full Text Available Conformational ensembles are increasingly recognized as a useful representation to describe fundamental relationships between protein structure, dynamics and function. Here we present an ensemble of ubiquitin in solution that is created by sampling conformational space without experimental information using "Backrub" motions inspired by alternative conformations observed in sub-Angstrom resolution crystal structures. Backrub-generated structures are then selected to produce an ensemble that optimizes agreement with nuclear magnetic resonance (NMR Residual Dipolar Couplings (RDCs. Using this ensemble, we probe two proposed relationships between properties of protein ensembles: (i a link between native-state dynamics and the conformational heterogeneity observed in crystal structures, and (ii a relation between dynamics of an individual protein and the conformational variability explored by its natural family. We show that the Backrub motional mechanism can simultaneously explore protein native-state dynamics measured by RDCs, encompass the conformational variability present in ubiquitin complex structures and facilitate sampling of conformational and sequence variability matching those occurring in the ubiquitin protein family. Our results thus support an overall relation between protein dynamics and conformational changes enabling sequence changes in evolution. More practically, the presented method can be applied to improve protein design predictions by accounting for intrinsic native-state dynamics.

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

    International Nuclear Information System (INIS)

    Stevens, S W; Rosser, K E; Bedford, J L

    2011-01-01

    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 -1 were recorded for open fields (relative to 320 MU min -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.

  11. The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET

    Directory of Open Access Journals (Sweden)

    Mengyi Yang

    2018-01-01

    Full Text Available Summary: Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. : Yang et al. revealed significant conformational dynamics of Cas9 at global and local scales using single-molecule FRET. They uncovered surprising long-range allosteric communication between the HNH nuclease domain and the RNA/DNA heteroduplex at the PAM-distal end that serves as a proofreading checkpoint to govern the nuclease activity and specificity of Cas9. Keywords: CRISPR, Cas9, single-molecule, FRET, conformational dynamics, proofreading, off-target, allosteric communication, genome editing

  12. Large-scale conformational changes of Trypanosoma cruzi proline racemase predicted by accelerated molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    César Augusto F de Oliveira

    2011-10-01

    Full Text Available Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi, is a life-threatening illness affecting 11-18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery.

  13. Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Zeynab Mohammad Hosseini Naveh

    Full Text Available Despite the large number of studies available on nicotinic acetylcholine receptors, a complete account of the mechanistic aspects of their gating transition in response to ligand binding still remains elusive. As a first step toward dissecting the transition mechanism by accelerated sampling techniques, we study the ligand-induced conformational changes of the acetylcholine binding protein (AChBP, a widely accepted model for the full receptor extracellular domain. Using unbiased Molecular Dynamics (MD and Temperature Accelerated Molecular Dynamics (TAMD simulations we investigate the AChBP transition between the apo and the agonist-bound state. In long standard MD simulations, both conformations of the native protein are stable, while the agonist-bound structure evolves toward the apo one if the orientation of few key sidechains in the orthosteric cavity is modified. Conversely, TAMD simulations initiated from the native conformations are able to produce the spontaneous transition. With respect to the modified conformations, TAMD accelerates the transition by at least a factor 10. The analysis of some specific residue-residue interactions points out that the transition mechanism is based on the disruption/formation of few key hydrogen bonds. Finally, while early events of ligand dissociation are observed already in standard MD, TAMD accelerates the ligand detachment and, at the highest TAMD effective temperature, it is able to produce a complete dissociation path in one AChBP subunit.

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

    International Nuclear Information System (INIS)

    Zhu, Jiajian; Sun, Zhiwei; Li, Zhongshan; Ehn, Andreas; Aldén, Marcus; Salewski, Mirko; Leipold, Frank; Kusano, Yukihiro

    2014-01-01

    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 emission of the gliding arc were investigated by optical methods. High-speed photography was utilized to reveal flow-rate dependent dynamics such as ignitions, propagation, short-cutting events, extinctions and conversions of the discharge from glowtype to spark-type. Short-cutting events and ignitions occur more frequently at higher flow rates. The anchor points of the gliding arc are mostly steady at the top of the electrodes at lower flow rates whereas at higher flow rates they glide up along the electrodes most of the time. The afterglow of fully developed gliding arcs is observed to decay over hundreds of microseconds after being electronically short-cut by a newly ignited arc. The extinction time decreases with the increase of the flow rate. The frequency of the conversion of a discharge from glow-type to spark-type increases with the flow rate. Additionally, spatial distributions of ground-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 and it is found that the emission intensity of NO γ (A-X), OH (A-X) and N 2 (C-B) increase with the flow rates showing more characteristics of spark-type arcs. The observed phenomena indicate the significance of the interaction between local turbulence and the gliding arc. (paper)

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

    Science.gov (United States)

    Zhu, Jiajian; Sun, Zhiwei; Li, Zhongshan; Ehn, Andreas; Aldén, Marcus; Salewski, Mirko; Leipold, Frank; Kusano, Yukihiro

    2014-07-01

    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 emission of the gliding arc were investigated by optical methods. High-speed photography was utilized to reveal flow-rate dependent dynamics such as ignitions, propagation, short-cutting events, extinctions and conversions of the discharge from glowtype to spark-type. Short-cutting events and ignitions occur more frequently at higher flow rates. The anchor points of the gliding arc are mostly steady at the top of the electrodes at lower flow rates whereas at higher flow rates they glide up along the electrodes most of the time. The afterglow of fully developed gliding arcs is observed to decay over hundreds of microseconds after being electronically short-cut by a newly ignited arc. The extinction time decreases with the increase of the flow rate. The frequency of the conversion of a discharge from glow-type to spark-type increases with the flow rate. Additionally, spatial distributions of ground-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 and it is found that the emission intensity of NO γ (A-X), OH (A-X) and N2 (C-B) increase with the flow rates showing more characteristics of spark-type arcs. The observed phenomena indicate the significance of the interaction between local turbulence and the gliding arc.

  16. 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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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

  18. 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.

  19. Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator.

    Science.gov (United States)

    Casino, Patricia; Miguel-Romero, Laura; Huesa, Juanjo; García, Pablo; García-Del Portillo, Francisco; Marina, Alberto

    2018-01-09

    The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3-. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  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. Dosimetric comparison of RapidArc with fixed gantry dynamic IMRT for loco-regionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Wu Hao; Han Shukui; Sun Yan; Jiang Fan

    2010-01-01

    Objective: To compare the dosimetric difference of RapidArc and fixed gantry angle dynamic IMRT (dIMRT) for loco-regionally advanced nasopharyngeal carcinoma. Methods: Ten previously treated patients with loco-regionally advanced nasopharyngeal carcinoma were replanned with RapidArc and dIMRT, respectively. The prescription dose was GTV 70 Gy/33 f and PTV 60 Gy/33 f. All plans met the requirement: 95% of PTV was covered by 60 Gy. Dose-volume histogram data, isodose distribution, monitor units, and treatment time were compared. Results: Dose distribution has no significant difference between the two techniques. RapidArc reduced the dose of the brainstem, mandible, and other normal tissues compared with dIMRT. Mean monitor units were 589.5 and 1381.0 for RapidArc and dIMRT (reduced by 57% relatively). Mean treatment time was 2.33 min and 7.82 min for RapidArc and dIMRT (reduced by 70% relatively). Conclusions: Compared with dIMRT, RapidArc achieves equal target coverage and OAR sparing while using fewer monitor units and less time during radiotherapy for patient with loco-regionally advanced nasopharyngeal carcinoma. (authors)

  2. De novo protein structure prediction by dynamic fragment assembly and conformational space annealing.

    Science.gov (United States)

    Lee, Juyong; Lee, Jinhyuk; Sasaki, Takeshi N; Sasai, Masaki; Seok, Chaok; Lee, Jooyoung

    2011-08-01

    Ab initio protein structure prediction is a challenging problem that requires both an accurate energetic representation of a protein structure and an efficient conformational sampling method for successful protein modeling. In this article, we present an ab initio structure prediction method which combines a recently suggested novel way of fragment assembly, dynamic fragment assembly (DFA) and conformational space annealing (CSA) algorithm. In DFA, model structures are scored by continuous functions constructed based on short- and long-range structural restraint information from a fragment library. Here, DFA is represented by the full-atom model by CHARMM with the addition of the empirical potential of DFIRE. The relative contributions between various energy terms are optimized using linear programming. The conformational sampling was carried out with CSA algorithm, which can find low energy conformations more efficiently than simulated annealing used in the existing DFA study. The newly introduced DFA energy function and CSA sampling algorithm are implemented into CHARMM. Test results on 30 small single-domain proteins and 13 template-free modeling targets of the 8th Critical Assessment of protein Structure Prediction show that the current method provides comparable and complementary prediction results to existing top methods. Copyright © 2011 Wiley-Liss, Inc.

  3. 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.

  4. Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

    Science.gov (United States)

    Choy, Meng S; Li, Yang; Machado, Luciana E S F; Kunze, Micha B A; Connors, Christopher R; Wei, Xingyu; Lindorff-Larsen, Kresten; Page, Rebecca; Peti, Wolfgang

    2017-02-16

    Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. 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.

  6. Polarization and Segregation through Conformity Pressure and Voluntary Migration: Simulation Analysis of Co-Evolutionary Dynamics

    Directory of Open Access Journals (Sweden)

    Dai Zusai

    2017-11-01

    Full Text Available While conformity pressures people to assimilate in a community, an individual occasionally migrates among communities when the individual feels discomfort. These two factors cause segregation and cultural diversity within communities in the society. By embedding a migration dynamic into Kuran and Sandholm’s model (2008 of preference evolution, we build an agent-based model to see how the variance of preferences in the entire society quantitatively changes over time. We find from the Monte-Carlo simulations that, while preferences assimilate within a community, self-selected migrations enlarge the diversity of preferences over communities in the society. We further study how the arrival rate of migration opportunities and the degree of conformity pressures affect the variance of preferences.

  7. 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.

  8. Accessing a hidden conformation of the maltose binding protein using accelerated molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Denis Bucher

    2011-04-01

    Full Text Available Periplasmic binding proteins (PBPs are a large family of molecular transporters that play a key role in nutrient uptake and chemotaxis in Gram-negative bacteria. All PBPs have characteristic two-domain architecture with a central interdomain ligand-binding cleft. Upon binding to their respective ligands, PBPs undergo a large conformational change that effectively closes the binding cleft. This conformational change is traditionally viewed as a ligand induced-fit process; however, the intrinsic dynamics of the protein may also be crucial for ligand recognition. Recent NMR paramagnetic relaxation enhancement (PRE experiments have shown that the maltose binding protein (MBP - a prototypical member of the PBP superfamily - exists in a rapidly exchanging (ns to µs regime mixture comprising an open state (approx 95%, and a minor partially closed state (approx 5%. Here we describe accelerated MD simulations that provide a detailed picture of the transition between the open and partially closed states, and confirm the existence of a dynamical equilibrium between these two states in apo MBP. We find that a flexible part of the protein called the balancing interface motif (residues 175-184 is displaced during the transformation. Continuum electrostatic calculations indicate that the repacking of non-polar residues near the hinge region plays an important role in driving the conformational change. Oscillations between open and partially closed states create variations in the shape and size of the binding site. The study provides a detailed description of the conformational space available to ligand-free MBP, and has implications for understanding ligand recognition and allostery in related proteins.

  9. 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...

  10. Accuracy of Real-time Couch Tracking During 3-dimensional Conformal Radiation Therapy, Intensity Modulated Radiation Therapy, and Volumetric Modulated Arc Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Wilbert, Juergen; Baier, Kurt; Hermann, Christian; Flentje, Michael; Guckenberger, Matthias

    2013-01-01

    Purpose: To evaluate the accuracy of real-time couch tracking for prostate cancer. Methods and Materials: Intrafractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study; prostate motion had been monitored with the Calypso System. An industrial robot moved a phantom along these trajectories, motion was detected via an infrared camera system, and the robotic HexaPOD couch was used for real-time counter-steering. Residual phantom motion during real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of 3-dimensional conformal radiation therapy (3D-CRT), step-and-shoot intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Results: Motion of the prostate was largest in the anterior–posterior direction, with systematic (∑) and random (σ) errors of 2.3 mm and 2.9 mm, respectively; the prostate was outside a threshold of 5 mm (3D vector) for 25.0%±19.8% of treatment time. Real-time tracking reduced prostate motion to ∑=0.01 mm and σ = 0.55 mm in the anterior–posterior direction; the prostate remained within a 1-mm and 5-mm threshold for 93.9%±4.6% and 99.7%±0.4% of the time, respectively. Without real-time tracking, pass rates based on a γ index of 2%/2 mm in film dosimetry ranged between 66% and 72% for 3D-CRT, IMRT, and VMAT, on average. Real-time tracking increased pass rates to minimum 98% on average for 3D-CRT, IMRT, and VMAT. Conclusions: Real-time couch tracking resulted in submillimeter accuracy for prostate cancer, which transferred into high dosimetric accuracy independently of whether 3D-CRT, IMRT, or VMAT was used.

  11. Active Polymers — Emergent Conformational and Dynamical Properties: A Brief Review

    Science.gov (United States)

    Winkler, Roland G.; Elgeti, Jens; Gompper, Gerhard

    2017-10-01

    Active matter exhibits a wealth of emerging nonequilibrium behaviours. A paradigmatic example is the interior of cells, where active components, such as the cytoskeleton, are responsible for its structural organization and the dynamics of the various components. Of particular interest are the properties of polymers and filaments. The intimate coupling of thermal and active noise, hydrodynamic interactions, and polymer conformations implies the emergence of novel structural and dynamical features. In this article, we review recent theoretical and simulation developments and results for the structural and dynamical properties of polymers exposed to activity. Two- and three-dimensional filaments are considered propelled by different mechanisms such as active Brownian particles or hydrodynamically-coupled force dipoles.

  12. 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)

  13. 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)

  14. 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.

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

    Science.gov (United States)

    Shimer, D.W.; Lange, A.C.

    1995-05-23

    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. 5 Figs.

  16. 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.

  17. 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.

  18. Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands.

    Science.gov (United States)

    Sattin, Sara; Tao, Jiahui; Vettoretti, Gerolamo; Moroni, Elisabetta; Pennati, Marzia; Lopergolo, Alessia; Morelli, Laura; Bugatti, Antonella; Zuehlke, Abbey; Moses, Mike; Prince, Thomas; Kijima, Toshiki; Beebe, Kristin; Rusnati, Marco; Neckers, Len; Zaffaroni, Nadia; Agard, David A; Bernardi, Anna; Colombo, Giorgio

    2015-09-21

    Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 Å from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules' effects on Hsp90 enzymatic, conformational, co-chaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Rodriguez, Nathaniel; Bollen, Johan; Ahn, Yong-Yeol

    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.

  20. 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.

  1. The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET.

    Science.gov (United States)

    Yang, Mengyi; Peng, Sijia; Sun, Ruirui; Lin, Jingdi; Wang, Nan; Chen, Chunlai

    2018-01-09

    Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Toward improved target conformity for two spot scanning proton therapy delivery systems using dynamic collimation

    Science.gov (United States)

    Moignier, Alexandra; Gelover, Edgar; Smith, Blake R.; Wang, Dongxu; Flynn, Ryan T.; Kirk, Maura L.; Lin, Liyong; Solberg, Timothy D.; Lin, Alexander; Hyer, Daniel E.

    2016-01-01

    Purpose: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV. Methods: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm. Results: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%–15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%–13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%–9.8%; p < 0.001) and 6.3% (95% CI: 3.7%–9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity. Conclusions: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system. PMID:26936726

  3. Phenomenology of local scale invariance: from conformal invariance to dynamical scaling

    International Nuclear Information System (INIS)

    Henkel, Malte

    2002-01-01

    Statistical systems displaying a strongly anisotropic or dynamical scaling behaviour are characterized by an anisotropy exponent θ or a dynamical exponent z. For a given value of θ (or z), we construct local scale transformations, which can be viewed as scale transformations with a space-time-dependent dilatation factor. Two distinct types of local scale transformations are found. The first type may describe strongly anisotropic scaling of static systems with a given value of θ, whereas the second type may describe dynamical scaling with a dynamical exponent z. Local scale transformations act as a dynamical symmetry group of certain non-local free-field theories. Known special cases of local scale invariance are conformal invariance for θ=1 and Schroedinger invariance for θ=2. The hypothesis of local scale invariance implies that two-point functions of quasi primary operators satisfy certain linear fractional differential equations, which are constructed from commuting fractional derivatives. The explicit solution of these yields exact expressions for two-point correlators at equilibrium and for two-point response functions out of equilibrium. A particularly simple and general form is found for the two-time auto response function. These predictions are explicitly confirmed at the uniaxial Lifshitz points in the ANNNI and ANNNS models and in the aging behaviour of simple ferromagnets such as the kinetic Glauber-Ising model and the kinetic spherical model with a non-conserved order parameter undergoing either phase-ordering kinetics or non-equilibrium critical dynamics

  4. 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.

  5. Alfvénic Dynamics and Fine Structuring of Discrete Auroral Arcs: Swarm and e-POP Observations

    Science.gov (United States)

    Miles, D.; Mann, I. R.; Pakhotin, I.; Burchill, J. K.; Howarth, A. D.; Knudsen, D. J.; Wallis, D. D.; Yau, A. W.; Lysak, R. L.

    2017-12-01

    The electrodynamics associated with dual discrete arc aurora with anti-parallel flow along the arcs were observed nearly simultaneously by the enhanced Polar Outflow Probe (e-POP) and the Swarm A and C spacecraft. Auroral imaging from e-POP reveal 1-10 km structuring of the arcs, which move and evolve on second timescales and confound the traditional single-spacecraft field-aligned current algorithms. High-cadence magnetic data from e-POP shows 1-10 Hz, presumably Alfvénic perturbations co-incident with and at the same scale size as the observed dynamic auroral fine structures. High-cadence electric and magnetic field data from Swarm A reveals non-stationary electrodynamics involving reflected and interfering Alfvén waves and signatures of modulation consistent with trapping in the Ionospheric Alfvén Resonator (IAR). Together, these observations suggest a role for Alfven waves, perhaps also the IAR, in discrete arc dynamics on 0.2 - 10s timescales and 1-10 km spatial scales.

  6. 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

  7. 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

  8. A variational conformational dynamics approach to the selection of collective variables in metadynamics

    Science.gov (United States)

    McCarty, James; Parrinello, Michele

    2017-11-01

    In this paper, we combine two powerful computational techniques, well-tempered metadynamics and time-lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy landscapes. Metadynamics is a well-established and widely used enhanced sampling method whose efficiency depends on an appropriate choice of collective variables. Often the initial choice is not optimal leading to slow convergence. However by analyzing the dynamics generated in one such run with a time-lagged independent component analysis and the techniques recently developed in the area of conformational dynamics, we obtain much more efficient collective variables that are also better capable of illuminating the physics of the system. We demonstrate the power of this approach in two paradigmatic examples.

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

    International Nuclear Information System (INIS)

    Konstandin, Thomas; Servant, Géraldine

    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 ∼ 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

  10. 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.

  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. 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

    CSPs use filtering techniques such as arc consistency, which also have been adapted to handle DCSPs with binary constraints. However, there exists only one algorithm targeting non-binary DCSPs (DnGAC4). In this paper we present a new algorithm DnSTR for maintaining arc consistency in DCSPs with non-binary...

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

    International Nuclear Information System (INIS)

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

    2017-01-01

    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. (paper)

  14. 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.

  15. Dynamic crushing of uniform and density graded cellular structures based on the circle arc model

    Directory of Open Access Journals (Sweden)

    Jianjun Zhang

    Full Text Available AbstractA new circle-arc model was established to present the cellular structure. Dynamic response of models with density gradients under constant velocities is investigated by employing Ls-dyna 971. Compared with the uniform models, the quasi-static plateau stress of different layers seems a significant parameter correlated with the deformation mode except for inertia effect when the density gradient is introduced. The impact velocity becomes much more vital on the deformation of the unit cell than the density gradient. The stress at both the impact and stationary sides is investigated in details. Furthermore, the stress-strain curve is compared with the modified shock wave theory. The density gradient does have some remarkable influence on the energy absorption capability, and a certain density gradient is not always beneficial to the energy absorption. Irrespective of the impact velocity, there seems always a critical strain where the energy absorbed by all these specimens could approximate to nearly the same value. So the critical strain-velocity curve is plotted and gives the beneficial area for energy absorption pertinent to density gradients and impact velocity.

  16. Solid state nuclear magnetic resonance spectroscopy of polymer thin films: chain conformation, dynamics, and morphology

    International Nuclear Information System (INIS)

    Nasreddine, V.F.

    2003-01-01

    This dissertation presents solid-state NMR studies of the chain conformation, dynamics and morphology of three adsorbed polymer systems: two random semi-crystalline copolymers, poly(ethylene-co-acrylic acid) (PEA) and poly(propylene-co-acrylic acid) (PPA), and an amorphous homopolymer, poly(n-butyl methacrylate) (PnBMA). Zirconia (ZrO 2 ) was chosen as the substrate for all three polymers since the binding of carboxylic acids to this metal oxide is well understood. The choice of polymers was based on their particular bulk conformational and dynamic properties as well as their common use in polymer coatings. These studies are motivated by the general lack of a microscopic picture of adsorbed polymers, which can be provided by NMR, and the relevance of chain conformation and dynamics to important polymer film properties such as adhesion. First the chain conformation and surface binding of adsorbed PEA as a function of acrylic acid content are characterized by 13 C cross polarization - magic angle spinning (CP-MAS), 2D 1 H- 13 C wideline separation (WISE) and 1 H spin diffusion NMR experiments and FTIR-PAS (Fourier transform infrared photoacoustic spectroscopy) measurements. The most important finding is that the chain conformation of adsorbed PEA is determined primarily by the sticker group density rather than the surface coverage. The second study of PEA concerns the chain dynamics in the bulk and adsorbed states. Variable temperature NMR experiments provide evidence that ethylene segments of adsorbed PEA form partially folded loops rather than flat extended trains. Finally 129 Xe NMR studies, used to probe the morphology of adsorbed PEA, show a bulk-like signal only for the highest loadings. The second system investigated, PPA, is another semi-crystalline random copolymer which binds to zirconia via carboxylate linkages. The 13 C CP-MAS NMR spectra of adsorbed PPAC unexpectedly show splittings normally associated with chain-chain packing in the crystalline regions

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

    International Nuclear Information System (INIS)

    Audet, Chantal; Poffenbarger, Brett A.; Chang, Pauling; Jackson, Paul S.; Lundahl, Robert E.; Ryu, Stephen I.; Ray, Gordon R.

    2011-01-01

    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, ∼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 ∼4 arc VMAT treatment plans using calibrated film dosimetry. Results: The CI (0-1 best) average for all plans was best for ∼4 noncoplanar arc VMAT at 0.86 compared with ∼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 50% ) were lowest for the four arc VMAT [RA(4)] and DCA plans. The average ratio of the V 50% for the other plans to the RA(4) V 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 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 organ at risk. The highest dose gradient

  18. 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.

  19. Characterizing highly dynamic conformational states: The transcription bubble in RNAP-promoter open complex as an example

    Science.gov (United States)

    Lerner, Eitan; Ingargiola, Antonino; Weiss, Shimon

    2018-03-01

    Bio-macromolecules carry out complicated functions through structural changes. To understand their mechanism of action, the structure of each step has to be characterized. While classical structural biology techniques allow the characterization of a few "structural snapshots" along the enzymatic cycle (usually of stable conformations), they do not cover all (and often fast interconverting) structures in the ensemble, where each may play an important functional role. Recently, several groups have demonstrated that structures of different conformations in solution could be solved by measuring multiple distances between different pairs of residues using single-molecule Förster resonance energy transfer (smFRET) and using them as constrains for hybrid/integrative structural modeling. However, this approach is limited in cases where the conformational dynamics is faster than the technique's temporal resolution. In this study, we combine existing tools that elucidate sub-millisecond conformational dynamics together with hybrid/integrative structural modeling to study the conformational states of the transcription bubble in the bacterial RNA polymerase-promoter open complex (RPo). We measured microsecond alternating laser excitation-smFRET of differently labeled lacCONS promoter dsDNA constructs. We used a combination of burst variance analysis, photon-by-photon hidden Markov modeling, and the FRET-restrained positioning and screening approach to identify two conformational states for RPo. The experimentally derived distances of one conformational state match the known crystal structure of bacterial RPo. The experimentally derived distances of the other conformational state have characteristics of a scrunched RPo. These findings support the hypothesis that sub-millisecond dynamics in the transcription bubble are responsible for transcription start site selection.

  20. Conformational dynamics of Escherichia coli flavodoxins in apo- and holo-states by solution NMR spectroscopy.

    Directory of Open Access Journals (Sweden)

    Qian Ye

    Full Text Available Flavodoxins are a family of small FMN-binding proteins that commonly exist in prokaryotes. They utilize a non-covalently bound FMN molecule to act as the redox center during the electron transfer processes in various important biological pathways. Although extensive investigations were performed, detailed molecular mechanisms of cofactor binding and electron transfer remain elusive. Herein we report the solution NMR studies on Escherichia coli flavodoxins FldA and YqcA, belonging to the long-chain and short-chain flavodoxin subfamilies respectively. Our structural studies demonstrate that both proteins show the typical flavodoxin fold, with extensive conformational exchanges observed near the FMN binding pocket in their apo-forms. Cofactor binding significantly stabilizes both proteins as revealed by the extension of secondary structures in the holo-forms, and the overall rigidity shown by the backbone dynamics data. However, the 50 s loops of both proteins in the holo-form still show conformational exchanges on the µs-ms timescales, which appears to be a common feature in the flavodoxin family, and might play an important role in structural fine-tuning during the electron transfer reactions.

  1. Particle dynamics around time conformal regular black holes via Noether symmetries

    Science.gov (United States)

    Jawad, Abdul; Umair Shahzad, M.

    The time conformal regular black hole (RBH) solutions which are admitting the time conformal factor e𝜖g(t), where g(t) is an arbitrary function of time and 𝜖 is the perturbation parameter are being considered. The approximate Noether symmetries technique is being used for finding the function g(t) which leads to t α. The dynamics of particles around RBHs are also being discussed through symmetry generators which provide approximate energy as well as angular momentum of the particles. In addition, we analyze the motion of neutral and charged particles around two well known RBHs such as charged RBH using Fermi-Dirac distribution and Kehagias-Sftesos asymptotically flat RBH. We obtain the innermost stable circular orbit and corresponding approximate energy and angular momentum. The behavior of effective potential, effective force and escape velocity of the particles in the presence/absence of magnetic field for different values of angular momentum near horizons are also being analyzed. The stable and unstable regions of particle near horizons due to the effect of angular momentum and magnetic field are also explained.

  2. Probing Conformational Dynamics of Tau Protein by Hydrogen/Deuterium Exchange Mass Spectrometry

    Science.gov (United States)

    Huang, Richard Y.-C.; Iacob, Roxana E.; Sankaranarayanan, Sethu; Yang, Ling; Ahlijanian, Michael; Tao, Li; Tymiak, Adrienne A.; Chen, Guodong

    2018-01-01

    Fibrillization of the microtubule-associated protein tau has been recognized as one of the signature pathologies of the nervous system in Alzheimer's disease, progressive supranuclear palsy, and other tauopathies. The conformational transition of tau in the fibrillization process, tau monomer to soluble aggregates to fibrils in particular, remains unclear. Here we report on the use of hydrogen/deuterium exchange mass spectrometry (HDX-MS) in combination with other biochemical approaches, including Thioflavin S fluorescence measurements, enzyme-linked immunosorbent assay (ELISA), and Western blotting to understand the heparin-induced tau's fibrillization. HDX-MS studies including anti-tau antibody epitope mapping experiments provided molecular level details of the full-length tau's conformational dynamics and its regional solvent accessibility upon soluble aggregates formation. The results demonstrate that R3 region in the full-length tau's microtubule binding repeat region (MTBR) is stabilized in the aggregation process, leaving both N and C terminal regions to be solvent exposed in the soluble aggregates and fibrils. The findings also illustrate the practical utility of orthogonal analytical methodologies for the characterization of protein higher order structure. [Figure not available: see fulltext.

  3. 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....

  4. 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...

  5. 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).

  6. Molecular dynamics coupled with a virtual system for effective conformational sampling.

    Science.gov (United States)

    Hayami, Tomonori; Kasahara, Kota; Nakamura, Haruki; Higo, Junichi

    2018-07-15

    An enhanced conformational sampling method is proposed: virtual-system coupled canonical molecular dynamics (VcMD). Although VcMD enhances sampling along a reaction coordinate, this method is free from estimation of a canonical distribution function along the reaction coordinate. This method introduces a virtual system that does not necessarily obey a physical law. To enhance sampling the virtual system couples with a molecular system to be studied. Resultant snapshots produce a canonical ensemble. This method was applied to a system consisting of two short peptides in an explicit solvent. Conventional molecular dynamics simulation, which is ten times longer than VcMD, was performed along with adaptive umbrella sampling. Free-energy landscapes computed from the three simulations mutually converged well. The VcMD provided quicker association/dissociation motions of peptides than the conventional molecular dynamics did. The VcMD method is applicable to various complicated systems because of its methodological simplicity. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  7. Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation

    Science.gov (United States)

    Hudson, Brian D.; George, Ashley R.; Ford, Martyn G.; Livingstone, David J.

    1992-04-01

    Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.

  8. Lesser Antillean Arc Initiation and Migration as a Proxy of Slab Dynamics: Geothermochronology, Thermobarometry and Structure of Saint Martin Granodiorites

    Science.gov (United States)

    Noury, M.; Münch, P.; Philippon, M. M.; Bernet, M.; Bruguier, O.; Balvay, M.

    2017-12-01

    In subduction zones, volcanic arc initiation, cessation, migration and associated upper plate deformation -i.e faulting and vertical motions- reflect large-scale slab dynamics. At the northeastern edge of the Caribbean plate, the Greater Caribbean subduction zone waned out during the Mid Eocene, following the subduction of the Bahamas bank. This arc cessation was contemporaneous with (i) a plate boundary re-organization (evolving from subduction to transform), (ii) upper plate deformation and (iii) arc initiation in the Lesser Antilles. As part of the GAARANTI project that aims at unraveling the relationships between the evolution of terrestrial Caribbean biodiversity and vertical motions resulting from the Lesser Antilles subduction zone dynamic, we study the Saint Martin granodiorites, one of the two Oligocene plutons outcropping in the Lesser Antillean forearc. We investigate the birth and evolution of the Lesser Antillean arc and its thermo-mechanical impact on the Caribbean upper plate. In order to characterize the P,T,t path of the pluton we performed several thermochronological analyses covering a wide range of temperature (U-Pb on zircon -Tc 850°C, Ar/Ar on amphibole -Tc 550°C- and biotite -Tc 325°C-, zircon and apatite fission-tracks -Tc 250 and 110°C, respectively as well as U-Th/He on apatite -Tc 60°C) coupled with in-situ thermobarometry analyses (Al in hornblendes) and structural data. Geochronology and thermobarometry reveal that the granodiorites emplaced at ca. 28 Ma, at a depth of 5 km. Based on the age difference between amphibole and biotite Ar/Ar ages, we show that the northern pluton cooled faster than the southern one. Preliminary thermochronological results show a fast cooling between 29 and 25 Ma and then a continuous and slow cooling since 25 Ma and inverse modeling points to a 10 Ma cooling event. Our investigations give insights on the thermo-mechanical evolution of the arc-forearc region of the Lesser Antilles subduction zone

  9. Molecular dynamics simulations reveal the conformational dynamics of Arabidopsis thaliana BRI1 and BAK1 receptor-like kinases.

    Science.gov (United States)

    Moffett, Alexander S; Bender, Kyle W; Huber, Steven C; Shukla, Diwakar

    2017-07-28

    The structural motifs responsible for activation and regulation of eukaryotic protein kinases in animals have been studied extensively in recent years, and a coherent picture of their activation mechanisms has begun to emerge. In contrast, non-animal eukaryotic protein kinases are not as well understood from a structural perspective, representing a large knowledge gap. To this end, we investigated the conformational dynamics of two key Arabidopsis thaliana receptor-like kinases, brassinosteroid-insensitive 1 (BRI1) and BRI1-associated kinase 1 (BAK1), through extensive molecular dynamics simulations of their fully phosphorylated kinase domains. Molecular dynamics simulations calculate the motion of each atom in a protein based on classical approximations of interatomic forces, giving researchers insight into protein function at unparalleled spatial and temporal resolutions. We found that in an otherwise "active" BAK1 the αC helix is highly disordered, a hallmark of deactivation, whereas the BRI1 αC helix is moderately disordered and displays swinging behavior similar to numerous animal kinases. An analysis of all known sequences in the A. thaliana kinome found that αC helix disorder may be a common feature of plant kinases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. 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.

  11. Molecular Dynamics Simulations of the STAS Domains of Rat Prestin and Human Pendrin Reveal Conformational Motions in Conserved Flexible Regions

    Directory of Open Access Journals (Sweden)

    Alok K. Sharma

    2014-02-01

    Full Text Available Background: Molecular dynamics (MD simulations provide valuable information on the conformational changes that accompany time-dependent motions in proteins. The reported crystal structure of rat prestin (PDB 3LLO is remarkable for an α1-α2 inter-helical angle that differs substantially from those observed in bacterial STAS domains of SulP anion transporters and anti-sigma factor antagonists. However, NMR data on the rat prestin STAS domain in solution suggests dynamic features at or near the α1-α2 helical region (Pasqualetto et al JMB, 2010. We therefore performed a 100 ns 300K MD simulation study comparing the STAS domains of rat prestin and (modeled human pendrin, to explore possible conformational flexibility in the region of the α1 and α2 helices. Methods: The conformation of the loop missing in the crystal structure of rat prestin STAS (11 amino acids between helix α1 and strand β3 was built using Modeller. MD simulations were performed with GROMACSv4.6 using GROMOS96 53a6 all-atom force field. Results: A subset of secondary structured elements of the STAS domains exhibits significant conformational changes during the simulation time course. The conformationally perturbed segments include the majority of loop regions, as well as the α1 and α2 helices. A significant decrease in the α1-α2 inter-helical angle observed across the simulation trajectory leads to closer helical packing at their C-termini. The end-simulation conformations of the prestin and pendrin STAS domains, including their decreased α1-α2 inter-helical angles, resemble more closely the packing of corresponding helices in the STAS structures of bacterial SulP transporters Rv1739c and ychM, as well as those of the anti-sigma factor antagonists. Several structural segments of the modeled human pendrin STAS domain exhibit larger atomic motions and greater conformational deviations than the corresponding regions of rat prestin, predicting that the human pendrin STAS

  12. Conformity, Anticonformity and Polarization of Opinions: Insights from a Mathematical Model of Opinion Dynamics

    Directory of Open Access Journals (Sweden)

    Tyll Krueger

    2017-07-01

    Full Text Available 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 or to control polarized debates and predict their outcomes. In this paper, we present a version of the q-voter model of opinion dynamics with two types of responses to social influence: conformity (like in the original q-voter model and anticonformity. We put the model on a social network with the double-clique topology in order to check how the interplay between those responses impacts the opinion dynamics in a population divided into two antagonistic segments. The model is analyzed analytically, numerically and by means of Monte Carlo simulations. Our results show that the system undergoes two bifurcations as the number of cross-links between cliques changes. Below the first critical point, consensus in the entire system is possible. Thus, two antagonistic cliques may share the same opinion only if they are loosely connected. Above that point, the system ends up in a polarized state.

  13. 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.

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

    Science.gov (United States)

    Han, Eun Young; Kim, Dong-Wook; Zhang, Xin; Penagaricano, Jose; Liang, Xiaoying; Hardee, Matthew; Morrill, Steve; Ratanatharathorn, Vaneerat

    2015-01-01

    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. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Silvia Lovera

    2015-11-01

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

  16. Conformation Analysis of T1 Lipase on Alcohols Solvent using Molecular Dynamics Simulation

    Science.gov (United States)

    Putri, A. M.; Sumaryada, T.; Wahyudi, S. T.

    2017-07-01

    Biodiesel usually is produced commercially via a transesterification reaction of vegetable oil with alcohol and alkali catalyst. The alkali catalyst has some drawbacks, such as the soap formation during the reaction. T1 Lipase enzyme had been known as a thermostable biocatalyst which is able to produce biodiesel through a cleaner process. In this paper the performance of T1 lipase enzyme as catalyst for transesterification reaction in pure ethanol, methanol, and water solvents were studied using a Molecular Dynamics (MD) Simulation at temperature of 300 K for 10 nanoseconds. The results have shown that in general the conformation of T1 lipase enzyme in methanol is more dynamics as shown by the value of root mean square deviation (RMSD), root mean squared fluctuation (RMSF), and radius of gyration. The highest solvent accessible surface area (SASA) total was also found in methanol due to the contribution of non-polar amino acid in the interior of the protein. Analysis of MD simulation has also revealed that the enzyme structure tend to be more rigid in ethanol environment. The analysis of electrostatic interactions have shown that Glu359-Arg270 salt-bridge pair might hold the key of thermostability of T1 lipase enzyme as shown by its strong and stable binding in all three solvents.

  17. Emerging paradigm in radiobiology in concept and practices of hypo fractionated conformal radiotherapy

    International Nuclear Information System (INIS)

    Mishra, S.P.; Srivastava, Anoop Kumar; Rastogi, Madhup; Khurana, Rohini; Pawaskar, Asawari

    2016-01-01

    This study has been performed in clinical setting by creating the treatment plan in dynamic conformal arc mode as the treatment delivery technique; with add on collimator APEX system having 56 pairs of 2.5 mm each as treatment unit. Photon beam energy selected for the study was 6 MV. Various number of treatment arcs were applied depending upon the location of the PTV. The PTV was prescribed a total dose of 60 Gy in five fractions

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

    International Nuclear Information System (INIS)

    Martín-García, Fernando; Mendieta-Moreno, Jesús Ignacio; Mendieta, Jesús; Gómez-Puertas, Paulino

    2012-01-01

    Highlights: ► Initial conformational change of paramyxovirus F protein is caused only by mechanical forces. ► HRA region undergoes a structural change from a beta + alpha conformation to an extended coil and then to an all-alpha conformation. ► HRS domains of F protein form three single α-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 β-sheet conformation to an elongated coil and then spontaneously to an α-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. Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)

    Energy Technology Data Exchange (ETDEWEB)

    McGarry, Conor K; Hounsell, Alan R [Radiotherapy Physics, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast (United Kingdom); Butterworth, Karl T; Trainor, Colman; O' Sullivan, Joe M; Prise, Kevin M, E-mail: conor.mcgarry@belfasttrust.hscni.net [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast (United Kingdom)

    2011-04-21

    A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

  20. Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)

    International Nuclear Information System (INIS)

    McGarry, Conor K; Hounsell, Alan R; Butterworth, Karl T; Trainor, Colman; O'Sullivan, Joe M; Prise, Kevin M

    2011-01-01

    A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

  1. 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

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

    International Nuclear Information System (INIS)

    Laurence, Ted Alfred

    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. Location and dynamical peculiarities of auroral arcs during activations of different intensity

    International Nuclear Information System (INIS)

    Kozelova, T.V.; Pudovkin, M.I.; Kornilova, T.A.

    1991-01-01

    It is shown that the location of a flare arc with respect to the precipitation area of energetic electrons is one of substorm characteristics. Severe substorms begin with activization inside this area. The explosive phase of a weak substorm beginning outside the energetic electron precipitation area involves a series of activizations, in which every next activization mainly lies at the lower latitude

  4. 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 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......-derived Boltzmann distribution. The macrocyclic ring system cyclododecane was subjected to an MD simulation at 1000 K and 71 different conformations could be sampled. These conformations were compared with the results of previously reported conformational analyses using stochastic search methods, and the MD method...

  5. Conformal coupling associated with the Noether symmetry and its connection with the ΛCDM dynamics

    International Nuclear Information System (INIS)

    De Souza, Rudinei C; Kremer, Gilberto M

    2013-01-01

    The aim of this work is to investigate a non-minimally coupled scalar field model through the Noether symmetry approach, with the radiation, matter and cosmological constant eras being analyzed. The Noether symmetry condition allows a conformal coupling and by means of a change of coordinates in the configuration space the field equations can be reduced to a single equation, which is of the form of the Friedmann equation for the ΛCDM model. In this way, it is formally shown that the dynamical system can furnish solutions with the same form as those of the ΛCDM 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 ΛCDM picture. Observational constraints on the variation of the gravitational constant can be imposed on the model through the initial condition of the scalar field. (paper)

  6. 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 (ΔGu H 2 0) for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from. PMID:25617632

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Evaluation of the dose distribution of dynamic conical conformal therapy using a C-arm mounted accelerator

    International Nuclear Information System (INIS)

    Nakagawa, Keiichi; Aoki, Yukimasa; Ohtomo, Kuni

    2001-01-01

    Conformal radiation therapy, which is widely utilized in Japan as a standard, highly precise technique has limited advantage in dose confinement because of its coplanar beam entry. An improved form of conformal therapy is delivered by a linac mounted on a C-arm rotatable gantry. The linac head was designed to move along the C-arm with a maximum angle of 60 degrees. Simultaneous rotation of the gantry creates a Dynamic Conical irradiation technique. Dynamic Conical Conformal Therapy (Dyconic Therapy) was developed by combining the technique with continuous MLC motion based on beam's eye views of the target volume. Dose distributions were measured in a phantom using film densitometry and compared with conventional conformal radiation therapy. The measurements showed that the dose distribution conformed to the target shape identified by CT. In addition, the dose distribution for a cancer patient was evaluated through the use of DVHs generated by a treatment planning system. These measurements showed that the dose distribution along the patient's long axis conformed to the shape of the target volume. DVH analysis, however, did not indicate superiority of the present technique over the conventional technique. Angulation of the C-arm gantry allowed the primary beam to strike a larger area of the therapy room. This necessitated adding shielding to the walls and ceiling of the treatment room. It was confirmed that the leakage radiation was reduced to a negligible level by adding an iron plate 20 cm thick to several places on the side walls, by adding an iron plate 9 cm thick to several places on the ceiling, and by increasing the thickness of the concrete ceiling from 70 to 140 cm. The possible usefulness of Dyconic Therapy was confirmed. (author)

  12. Photo-dynamic therapy (pdt) for skin cancer using a xenon arc lamp with interference filters

    International Nuclear Information System (INIS)

    Hagekyriakou, J.

    2004-01-01

    Full text: Phototherapy involves the production of photochemical reactions in cells by the direct action of light, including Ultra Violet, leading to biological effects, including cell death. Photo Dynamic Therapy involves the application of light, at wavelengths and intensity which has no biological effects, in combination with a photosensitizing compound, which is biologically inert in the absence of light, which once located in cells, can produce cellular damage when activated by light of certain wavelengths. The active compound produced during PDT is singlet Oxygen which has a half life of 3 microseconds. This necessitates the use of very powerful light sources, such as lasers, in order to achieve treatment delivery within a reasonable time, say minutes. Even though PDT is very effective in the treatment of skin cancer using topically applied photosensitizing drugs, the cost of powerful lasers, required to produce light in the red part of the spectrum, has been prohibitively expensive for widespread application of the above technique. A 300 Watt Xenon arc light source, with tuneable wavelength and bandwidth, used predominantly for Forensic Science applications, manufactured by Rofin Australia Pty, Ltd, has been modified by the manufacturer, boosting the power to 500 Watts. A group of Interference filters have been specifically made to facilitate irradiation at 670nm, 620nm and 600 nm, at relatively narrow bandwidth, typically 50 nm. This would provide adequate penetration of the light, for a variety of skin cancers, depending on the thickness of the lesion and the skin type involved. A relatively broad band Ultra Violet interference filter has also been inserted in the instrument for observation of Fluorescence of the lesion prior to treatment, as an indicator of photosensitizing drug uptake by the lesion involved. Patients with skin cancers such as Basal Cell Carcinoma (BCC) and Paget's Extramammary disease were treated at the Peter MacCallum Cancer Centre

  13. Analysis of Variscan dynamics; early bending of the Cantabria-Asturias Arc, northern Spain

    Science.gov (United States)

    Kollmeier, J. M.; van der Pluijm, B. A.; Van der Voo, R.

    2000-08-01

    Calcite twinning analysis in the Cantabria-Asturias Arc (CAA) of northern Spain provides a basis for evaluating conditions of Variscan stress and constrains the arc's structural evolution. Twinning typically occurs during earliest layer-parallel shortening, offering the ability to define early conditions of regional stress. Results from the Somiedo-Correcilla region are of two kinds: early maximum compressive stress oriented layer-parallel and at high angles to bedding strike (D1 σ1) and later twin producing compression oriented sub-parallel to strike (D2 σ1). When all D1 compressions are rotated into a uniform east-west reference orientation, a quite linear, north-south trending fold-thrust belt results showing a slight deflection of the southern zone to the south-southeast. North-south-directed D2 σ1 compression was recorded prior to bending of the belt. Calcite twinning data elucidate earliest structural conditions that could not be obtained by other means, whereas the kinematics of arc tightening during D2 is constrained by paleomagnetism. A large and perhaps protracted D2 σ1 is suggested by our results, as manifested by approximately 50% arc tightening prior to acquisition of paleomagnetic remagnetizations throughout the CAA. Early east-west compression (D1 σ1) likely resulted from the Ebro-Aquitaine massif docking to Laurussia whereas the north-directed collision of Africa (D2 σ1) produced clockwise bending in the northern zone, radial folding in the hinge, and rotation of thrusts in the southern zone.

  14. Conformation radiotherapy and conformal radiotherapy

    International Nuclear Information System (INIS)

    Morita, Kozo

    1999-01-01

    In order to coincide the high dose region to the target volume, the 'Conformation Radiotherapy Technique' using the multileaf collimator and the device for 'hollow-out technique' was developed by Prof. S. Takahashi in 1960. This technique can be classified a type of 2D-dynamic conformal RT techniques. By the clinical application of this technique, the late complications of the lens, the intestine and the urinary bladder after radiotherapy for the maxillary cancer and the cervical cancer decreased. Since 1980's the exact position and shape of the tumor and the surrounding normal tissues can be easily obtained by the tremendous development of the CT/MRI imaging technique. As a result, various kinds of new conformal techniques such as the 3D-CRT, the dose intensity modulation, the tomotherapy have been developed since the beginning of 1990'. Several 'dose escalation study with 2D-/3D conformal RT' is now under way to improve the treatment results. (author)

  15. Effect of Chain Conformation on the Single-Molecule Melting Force in Polymer Single Crystals: Steered Molecular Dynamics Simulations Study.

    Science.gov (United States)

    Feng, Wei; Wang, Zhigang; Zhang, Wenke

    2017-02-28

    Understanding the relationship between polymer chain conformation as well as the chain composition within the single crystal and the mechanical properties of the corresponding single polymer chain will facilitate the rational design of high performance polymer materials. Here three model systems of polymer single crystals, namely poly(ethylene oxide) (PEO), polyethylene (PE), and nylon-66 (PA66) have been chosen to study the effects of chain conformation, helical (PEO) versus planar zigzag conformation (PE, PA66), and chain composition (PE versus PA66) on the mechanical properties of a single polymer chain. To do that, steered molecular dynamics simulations were performed on those polymer single crystals by pulling individual polymer chains out of the crystals. Our results show that the patterns of force-extension curve as well as the chain moving mode are closely related to the conformation of the polymer chain in the single crystal. In addition, hydrogen bonds can enhance greatly the force required to stretch the polymer chain out of the single crystal. The dynamic breaking and reformation of multivalent hydrogen bonds have been observed for the first time in PA66 at the single molecule level.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    at the expense of outward-facing conformations. The simulations predict, and we have observed experimentally, that presteady-state currents are blocked by saturating sugar, but not the changes in fluorescence. Thus we have isolated an electroneutral conformational change that has not been previously described......) was totally abolished, whereas Fmax was only reduced 50%. Phlorizin reduced both Qmax and Fmax (Ki 0.4 µM), with no changes in V0.5's or relaxation time constants. Simulations using an eight-state kinetic model indicate that external sugar increases the occupancy probability of inward-facing conformations...

  17. Dissipative particle dynamics of triblock copolymer melts: A midblock conformational study at moderate segregation

    Science.gov (United States)

    Tallury, Syamal S.; Spontak, Richard J.; Pasquinelli, Melissa A.

    2014-12-01

    As thermoplastic elastomers, triblock copolymers constitute an immensely important class of shape-memory soft materials due to their unique ability to form molecular networks stabilized by physical, rather than chemical, cross-links. The extent to which such networks develop in triblock and higher-order multiblock copolymers is sensitive to the formation of midblock bridges, which serve to connect neighboring microdomains. In addition to bridges, copolymer molecules can likewise form loops and dangling ends upon microphase separation or they can remain unsegregated. While prior theoretical and simulation studies have elucidated the midblock bridging fraction in triblock copolymer melts, most have only considered strongly segregated systems wherein dangling ends and unsegregated chains become relatively insignificant. In this study, simulations based on dissipative particle dynamics are performed to examine the self-assembly and networkability of moderately segregated triblock copolymers. Utilizing a density-based cluster-recognition algorithm, we demonstrate how the simulations can be analyzed to extract information about microdomain formation and permit explicit quantitation of the midblock bridging, looping, dangling, and unsegregated fractions for linear triblock copolymers varying in chain length, molecular composition, and segregation level. We show that midblock conformations can be sensitive to variations in chain length, molecular composition, and bead repulsion, and that a systematic investigation can be used to identify the onset of strong segregation where the presence of dangling and unsegregated fractions are minimal. In addition, because this clustering approach is robust, it can be used with any particle-based simulation method to quantify network formation of different morphologies for a wide range of triblock and higher-order multiblock copolymer systems.

  18. 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.

  19. Impact of an extruded nucleotide on cleavage activity and dynamic catalytic core conformation of the hepatitis delta virus ribozyme

    Czech Academy of Sciences Publication Activity Database

    Šefčíková, J.; Krasovská, Maryna V.; Špačková, Naďa; Šponer, Jiří; Walter, N.G.

    2007-01-01

    Roč. 85, 5-6 (2007), s. 392-406 ISSN 0006-3525 R&D Projects: GA ČR(CZ) GA203/05/0388; GA ČR(CZ) GA203/05/0009; GA AV ČR(CZ) 1QS500040581; GA MŠk(CZ) LC512 Institutional research plan: CEZ:AV0Z50040702 Keywords : conformational dynamics * hepatitis delta virus * molecular dynamics Subject RIV: BO - Biophysics Impact factor: 2.389, year: 2007

  20. Simulating molecular mechanisms of the MDM2-mediated regulatory interactions: a conformational selection model of the MDM2 lid dynamics.

    Directory of Open Access Journals (Sweden)

    Gennady M Verkhivker

    Full Text Available Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications and length of the lid. We found that the dynamic equilibrium between "closed" and "semi-closed" lid forms may be a fundamental characteristic of MDM2 regulatory interactions, which can be modulated by phosphorylation, phosphomimetic mutation as well as by the lid size. Our results revealed that these factors may regulate p53-MDM2 binding by fine-tuning the thermodynamic equilibrium between preexisting conformational states of apo-MDM2. In agreement with NMR studies, the effect of phosphorylation on MDM2 interactions was more pronounced with the truncated lid variant that favored the thermodynamically dominant closed form. The phosphomimetic mutation S17D may alter the lid dynamics by shifting the thermodynamic equilibrium towards the ensemble of "semi-closed" conformations. The dominant "semi-closed" lid form and weakened dependence on the phosphorylation seen in simulations with the complete lid can provide a rationale for binding of small p53-based mimetics and inhibitors without a direct competition with the lid dynamics. The results suggested that a conformational selection model of preexisting MDM2 states may provide a robust theoretical framework for understanding MDM2 dynamics. Probing biological functions and mechanisms of MDM2

  1. Evaluation of a mixed beam therapy for post-mastectomy breast cancer patients: bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy.

    Science.gov (United States)

    Zhang, Rui; Heins, David; Sanders, Mary; Guo, Beibei; Hogstrom, Kenneth

    2018-05-10

    The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left-sided post-mastectomy breast cancer patients. Mixed beam treatment plans were produced for nine post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT+IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs. 0.53, p 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm 3 ) between distal PTV surface and lung may benefit the most from mixed beam therapy. This work has demonstrated that mixed beam therapy (BECT+IMRT : VMAT = 4 : 1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating post-mastectomy patients, possibly leading to reduced normal tissue complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

    Science.gov (United States)

    Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

    2014-06-01

    Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Structure and conformational dynamics of the domain 5 RNA hairpin of a bacterial group II intron revealed by solution nuclear magnetic resonance and molecular dynamics simulations.

    Science.gov (United States)

    Pechlaner, Maria; Sigel, Roland K O; van Gunsteren, Wilfred F; Dolenc, Jožica

    2013-10-08

    Nuclear magnetic resonance (NMR) nuclear Overhauser enhancement (NOE) data obtained for a 35-nucleotide RNA segment of a bacterial group II intron indicate a helical hairpin structure in which three parts, a terminal pentaloop, a bulge, and a G-A mismatch, display no Watson-Crick base pairing. The 668 NOE upper distance bounds for atom pairs are insufficient to uniquely determine the conformation of these segments. Therefore, molecular dynamics simulations including time-averaged distance restraints have been used to obtain a conformational ensemble compatible with the observed NMR data. The ensemble shows alternating hydrogen bonding patterns for the mentioned segments. In particular, in the pentaloop and in the bulge, the hydrogen bonding networks correspond to distinct conformational clusters that could not be captured by using conventional single-structure refinement techniques. This implies that, to obtain a realistic picture of the conformational ensemble of such flexible biomolecules, it is necessary to properly account for the conformational variability in the structure refinement of RNA fragments.

  4. 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

  5. Conformational study of bovine lactoferricin in membrane-micking conditions by molecular dynamics simulation and circular dichroism.

    Science.gov (United States)

    Daidone, Isabella; Magliano, Alessandro; Di Nola, Alfredo; Mignogna, Giuseppina; Clarkson, Matilda Manuela; Lizzi, Anna Rita; Oratore, Arduino; Mazza, Fernando

    2011-04-01

    Lactoferricins are potent antimicrobial peptides released by pepsin cleavage of Lactoferrins. Bovine Lactoferricin (LfcinB) has higher activity than the intact bovine Lactoferrin, and is the most active among the other Lactoferricins of human, murine and caprine origin. In the intact protein the fragment corresponding to LfcinB is in an helical conformation, while in water LfcinB adopts an amphipathic β-hairpin structure. However, whether any of these structural motifs is the antibacterial active conformation, i.e., the one interacting with bacterial membrane components, remains to be seen. Here we present Circular Dichroism (CD) spectra and Molecular Dynamics (MD) simulations indicating that in membrane-mimicking solvents the LfcinB adopts an amphipathic β-hairpin structure similar to that observed in water, but differing in the dynamic behavior of the side-chains of the two tryptophan residues. In the membrane-mimicking solvent these side-chains show a high propensity to point towards the hydrophobic environment, rather than being in the hydrophobic core as seen in water, while the backbone preserves the hairpin conformation as found in water. These results suggest that the tryptophans might act as anchors pulling the stable, solvent-invariant hairpin structure into the membrane.

  6. Refining Markov state models for conformational dynamics using ensemble-averaged data and time-series trajectories

    Science.gov (United States)

    Matsunaga, Y.; Sugita, Y.

    2018-06-01

    A data-driven modeling scheme is proposed for conformational dynamics of biomolecules based on molecular dynamics (MD) simulations and experimental measurements. In this scheme, an initial Markov State Model (MSM) is constructed from MD simulation trajectories, and then, the MSM parameters are refined using experimental measurements through machine learning techniques. The second step can reduce the bias of MD simulation results due to inaccurate force-field parameters. Either time-series trajectories or ensemble-averaged data are available as a training data set in the scheme. Using a coarse-grained model of a dye-labeled polyproline-20, we compare the performance of machine learning estimations from the two types of training data sets. Machine learning from time-series data could provide the equilibrium populations of conformational states as well as their transition probabilities. It estimates hidden conformational states in more robust ways compared to that from ensemble-averaged data although there are limitations in estimating the transition probabilities between minor states. We discuss how to use the machine learning scheme for various experimental measurements including single-molecule time-series trajectories.

  7. Enrichment of Druggable Conformations from Apo Protein Structures Using Cosolvent-Accelerated Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Andrew Kalenkiewicz

    2015-04-01

    Full Text Available Here we describe the development of an improved workflow for utilizing experimental and simulated protein conformations in the structure-based design of inhibitors for anti-apoptotic Bcl-2 family proteins. Traditional structure-based approaches on similar targets are often constrained by the sparsity of available structures and difficulties in finding lead compounds that dock against flat, flexible protein-protein interaction surfaces. By employing computational docking of known small molecule inhibitors, we have demonstrated that structural ensembles derived from either accelerated MD (aMD or MD in the presence of an organic cosolvent generally give better scores than those assessed from analogous conventional MD. Furthermore, conformations obtained from combined cosolvent aMD simulations started with the apo-Bcl-xL structure yielded better average and minimum docking scores for known binders than an ensemble of 72 experimental apo- and ligand-bound Bcl-xL structures. A detailed analysis of the simulated conformations indicates that the aMD effectively enhanced conformational sampling of the flexible helices flanking the main Bcl-xL binding groove, permitting the cosolvent acting as small ligands to penetrate more deeply into the binding pocket and shape ligand-bound conformations not evident in conventional simulations. We believe this approach could be useful for identifying inhibitors against other protein-protein interaction systems involving highly flexible binding sites, particularly for targets with less accumulated structural data.

  8. Conformal Gravity

    International Nuclear Information System (INIS)

    Hooft, G.

    2012-01-01

    The dynamical degree of freedom for the gravitational force is the metric tensor, having 10 locally independent degrees of freedom (of which 4 can be used to fix the coordinate choice). In conformal gravity, we split this field into an overall scalar factor and a nine-component remainder. All unrenormalizable infinities are in this remainder, while the scalar component can be handled like any other scalar field such as the Higgs field. In this formalism, conformal symmetry is spontaneously broken. An imperative demand on any healthy quantum gravity theory is that black holes should be described as quantum systems with micro-states as dictated by the Hawking-Bekenstein theory. This requires conformal symmetry that may be broken spontaneously but not explicitly, and this means that all conformal anomalies must cancel out. Cancellation of conformal anomalies yields constraints on the matter sector as described by some universal field theory. Thus black hole physics may eventually be of help in the construction of unified field theories. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hongxia [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China); Wang, Yanwei, E-mail: wangyanwei@cnjsjk.cn [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China); Yang, Yong; Shu, Xin; Yan, Han [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China); Ran, Qianping, E-mail: qpran@cnjsjk.cn [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China)

    2017-06-15

    Highlights: • Adsorption conformation of comb-like PCE was studied by all-atom MD simulations. • A comparison is made between vacuum-based and solution-based simulations. • Effects of hydrophobic modifications on adsorption properties are elucidated. - Abstract: 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 (C{sub 2}S) 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 C{sub 2}S 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 C{sub 2}S surface and lowered the water density. Perturbations to the interfacial water density were found to correlate nicely with the adsorbed conformations of PCEs.

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

    KAUST Repository

    Serag, Maged F.

    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.

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

    KAUST Repository

    Serag, Maged F.; Abadi, Maram; Habuchi, Satoshi

    2014-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Junichi [Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, Okazaki 444-8585 (Japan); Takada, Shoji [Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, Okazaki 444-8585 (Japan); Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Saito, Shinji, E-mail: shinji@ims.ac.jp [Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, Okazaki 444-8585 (Japan); The Graduate University for Advanced Studies, Okazaki 444-8585 (Japan)

    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.

  13. 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

  14. 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.

  15. 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…

  16. 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.

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

    International Nuclear Information System (INIS)

    Falk, Marianne; Larsson, Tobias; Keall, Paul; Chul Cho, Byung; Aznar, Marianne; Korreman, Stine; Poulsen, Per; Munck af Rosenschoeld, Per

    2012-01-01

    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 by using a leaf position constraint (LPC) that reduces the difference in the position of adjacent MLC leaves in the plan. The purpose of this study was to investigate the impact of the LPC on the quality of inversely optimized arc radiotherapy plans and the effect of the MLC motion pattern 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 with a single 358 deg. arc were generated with LPC priorities of 0 (no LPC), 0.25, 0.5, 0.75, and 1 (highest possible LPC), respectively. All the plans had a prescribed dose of 2 Gy x 30, used 6 MV, a maximum dose rate of 600 MU/min and a collimator angle of 45 deg. or 315 deg. To quantify the plan modulation, an average adjacent leaf distance (ALD) was calculated by averaging the mean adjacent leaf distance for each control point. The linear relationship between the plan quality [i.e., the calculated dose distributions and the number of monitor units (MU)] and the LPC was investigated, and the linear regression coefficient as well as a two tailed confidence level of 95% was used in the evaluation. The effect of the plan modulation on the performance of MLC tracking was tested by delivering the plans to a cylindrical diode array phantom moving with sinusoidal motion in the superior-inferior direction with a peak-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

  18. Treatment of absolute painful glaucoma with dynamic arcs using novalis shaped beam radiosurgery

    International Nuclear Information System (INIS)

    Gonzalez-Olhovich, Irene; Celis, Miguel Angel; Larraga-Gutierrez, Jose; Lopez-Ayala, Temuchino; Suarez-Campos, Jose; Garcia-Garduno, Amanda; Herrera-Gomez, Leopoldo; Hernandez-Bojorquez, Mariana B.Sc.

    2006-01-01

    Purpose: We assessed the effect of shaped beam conformal stereotactic radiosurgery (SRS) in 1 patient with chronic painful glaucoma in one eye refractory to medical treatment. Methods and Materials: Left eye ciliary body was targeted at 18 Gy (90% isodose curve) with a dedicated linear accelerator (Novalis, BrainLAB, Germany) SRS. Interval follow-up was performed weekly for the first month, and every 2 months until 1 year was completed with clinical examinations and intraocular pressure (IOP) measurements. Results: Ocular pain resolved at 6 weeks after SRS treatment. IOP decreased and normalized at 1 year. Conclusions: We present a case in which SRS appears to be an effective treatment of chronic refractory painful glaucoma. Further Phase I studies are needed to know the best parameters for radiation dose, tolerance of organs at risk, and pathophysiologic effects

  19. Revisiting imidazolium based ionic liquids: Effect of the conformation bias of the [NTf2] anion studied by molecular dynamics simulations

    Science.gov (United States)

    Neumann, Jan; Golub, Benjamin; Odebrecht, Lisa-Marie; Ludwig, Ralf; Paschek, Dietmar

    2018-05-01

    We study ionic liquids composed of 1-alkyl-3-methylimidazolium cations and bis(trifluoromethyl-sulfonyl)imide anions ([CnMIm][NTf2]) with varying chain-length n = 2, 4, 6, 8 by using molecular dynamics simulations. We show that a reparametrization of the dihedral potentials as well as charges of the [NTf2] anion leads to an improvement of the force field model introduced by Köddermann, Paschek, and Ludwig [ChemPhysChem 8, 2464 (2007)] (KPL-force field). A crucial advantage of the new parameter set is that the minimum energy conformations of the anion (trans and gauche), as deduced from ab initio calculations and Raman experiments, are now both well represented by our model. In addition, the results for [CnMIm][NTf2] show that this modification leads to an even better agreement between experiment and molecular dynamics simulation as demonstrated for densities, diffusion coefficients, vaporization enthalpies, reorientational correlation times, and viscosities. Even though we focused on a better representation of the anion conformation, also the alkyl chain-length dependence of the cation behaves closer to the experiment. We strongly encourage to use the new NGOLP (Neumann, Golub, Odebrecht, Ludwig, Paschek) force field for the [NTf2] anion instead of the earlier KPL parameter set for computer simulations aiming to describe the thermodynamics, dynamics, and also structure of imidazolium-based ionic liquids.

  20. A molecular dynamics investigation of CDK8/CycC and ligand binding: conformational flexibility and implication in drug discovery

    Science.gov (United States)

    Cholko, Timothy; Chen, Wei; Tang, Zhiye; Chang, Chia-en A.

    2018-05-01

    Abnormal activity of cyclin-dependent kinase 8 (CDK8) along with its partner protein cyclin C (CycC) is a common feature of many diseases including colorectal cancer. Using molecular dynamics (MD) simulations, this study determined the dynamics of the CDK8-CycC system and we obtained detailed breakdowns of binding energy contributions for four type-I and five type-II CDK8 inhibitors. We revealed system motions and conformational changes that will affect ligand binding, confirmed the essentialness of CycC for inclusion in future computational studies, and provide guidance in development of CDK8 binders. We employed unbiased all-atom MD simulations for 500 ns on twelve CDK8-CycC systems, including apoproteins and protein-ligand complexes, then performed principal component analysis (PCA) and measured the RMSF of key regions to identify protein dynamics. Binding pocket volume analysis identified conformational changes that accompany ligand binding. Next, H-bond analysis, residue-wise interaction calculations, and MM/PBSA were performed to characterize protein-ligand interactions and find the binding energy. We discovered that CycC is vital for maintaining a proper conformation of CDK8 to facilitate ligand binding and that the system exhibits motion that should be carefully considered in future computational work. Surprisingly, we found that motion of the activation loop did not affect ligand binding. Type-I and type-II ligand binding is driven by van der Waals interactions, but electrostatic energy and entropic penalties affect type-II binding as well. Binding of both ligand types affects protein flexibility. Based on this we provide suggestions for development of tighter-binding CDK8 inhibitors and offer insight that can aid future computational studies.

  1. Dynamic Arc Fitting Path Follower for Skid-Steered Mobile Robots

    Directory of Open Access Journals (Sweden)

    Peter Lepej

    2015-10-01

    Full Text Available Many applications, such as surveillance, inspection or search and rescue operations, can be performed with autonomous robots. Our aim is a control of modular autonomous systems in rescue robotics. One of the basic problems with autonomous robotics is the execution part where the control commands (translation and rotational velocities are produced for mobile bases. Therefore we have focused on this area because there is only a small amount of available path following software for skid-steered mobile robots. Our goal was to develop a velocity controller that could be used for multiple skid-steered mobile bases. We considered differential drive mobile bases such as tracked skid-steering mobile bases. Our approach is based on an arc fitting algorithm, which takes into account the robot constraints and kinematical model. It produces a continuous trajectory where fitting to the given path is adapted based on given parameters. Moreover, we have included orientation angle compensation while the mobile robot is moving and ground inclination compensation. Our rescue robot is described, together with the simulation setup and algorithm implementation. We compared our algorithm to the Hector-based software and curvature velocity approach. The results for the proposed algorithm are shown for the simulation results and the experiment.

  2. Tectonomagmatic activity and ice dynamics in the Bransfield Strait back-arc basin, Antarctica

    Science.gov (United States)

    Dziak, Robert P.; Park, Minkyu; Lee, Won Sang; Matsumoto, Haru; Bohnenstiehl, Delwayne R.; Haxel, Joseph H.

    2010-01-01

    An array of moored hydrophones was used to monitor the spatiotemporal distribution of small- to moderate-sized earthquakes and ice-generated sounds within the Bransfield Strait, Antarctica. During a 2 year period, a total of 3900 earthquakes, 5925 icequakes and numerous ice tremor events were located throughout the region. The seismic activity included eight space-time earthquake clusters, positioned along the central neovolcanic rift zone of the young Bransfield back-arc basin. These sequences of small magnitude earthquakes, or swarms, suggest ongoing magmatic activity that becomes localized along isolated volcanic features and fissure-like ridges in the southwest portion of the basin. A total of 122 earthquakes were located along the South Shetland trench, indicating continued deformation and possibly ongoing subduction along this margin. The large number of icequakes observed show a temporal pattern related to seasonal freeze-thaw cycles and a spatial distribution consistent with channeling of sea ice along submarine canyons from glacier fronts. Several harmonic tremor episodes were sourced from a large (˜30 km2) iceberg that entered northeast portion of the basin. The spectral character of these signals suggests they were produced by either resonance of a small chamber of fluid within the iceberg, or more likely, due to periodicity of discrete stick-slip events caused by contact of the moving iceberg with the seafloor. These pressure waves appear to have been excited by abrasion of the iceberg along the seafloor as it passed Clarence and Elephant Islands.

  3. Dosimetric comparison of volumetric modulated arc therapy (VMAT), DMlC (Dynamic IMRT), and 3DCRT in left breast cancer after breast conserving surgery receiving left breast irradiation

    International Nuclear Information System (INIS)

    Pratibha, Bauskar; Vibhay, Pareek; Rajendra, Bhalavat; Chandra, Manish

    2016-01-01

    Previous studies have demonstrated that the risk of ischemic heart disease is increased as a result of exposure to ionizing radiation in women treated for breast cancer. Alternative radiation techniques, such as dynamic intensity-modulated radiation therapy (DMLC), volumetric-modulated arc therapy (VMAT), have been shown to improve dosimetric parameters of the heart and substructures. However, these techniques have not been compared with each other to potentially guide treatment decisions. Volumetric modulated arc therapy (VMAT) is a novel extension of conventional intensity-modulated radiotherapy (c-IMRT), in which an optimized three dimensional dose distribution may be delivered in a single gantry rotation. VMAT is the predecessor to Rapid-Arc (Varian Medical System). This study uses VMAT, DMLC and 3DCRT to compare target volume coverage and doses to organs at risk (OARs), especially lung and heart doses, using these three techniques in whole breast irradiation after breast conserving surgery in left breast cancer cases

  4. Dynamic stability of a curved pipe bent in the arc of a circle on hinge ...

    Indian Academy of Sciences (India)

    of numerical solution of the dynamic stability of a pipe in its plane are developed. An example of a ... Most scientific researches in the area of vibrations of pipes conveying liquids are concerned with investigation of ..... is good coincidence. 5.

  5. 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.

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

    International Nuclear Information System (INIS)

    Schmitz, D.; Shubert, V. A.; Giuliano, B. M.; Schnell, M.

    2014-01-01

    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

  7. Excited state conformational dynamics in carotenoids: dark intermediates and excitation energy transfer.

    Science.gov (United States)

    Beck, Warren F; Bishop, Michael M; Roscioli, Jerome D; Ghosh, Soumen; Frank, Harry A

    2015-04-15

    A consideration of the excited state potential energy surfaces of carotenoids develops a new hypothesis for the nature of the conformational motions that follow optical preparation of the S2 (1(1)Bu(+)) state. After an initial displacement from the Franck-Condon geometry along bond length alternation coordinates, it is suggested that carotenoids pass over a transition-state barrier leading to twisted conformations. This hypothesis leads to assignments for several dark intermediate states encountered in femtosecond spectroscopic studies. The Sx state is assigned to the structure reached upon the onset of torsional motions near the transition state barrier that divides planar and twisted structures on the S2 state potential energy surface. The X state, detected recently in two-dimensional electronic spectra, corresponds to a twisted structure well past the barrier and approaching the S2 state torsional minimum. Lastly, the S(∗) state is assigned to a low lying S1 state structure with intramolecular charge transfer character (ICT) and a pyramidal conformation. It follows that the bent and twisted structures of carotenoids that are found in photosynthetic light-harvesting proteins yield excited-state structures that favor the development of an ICT character and optimized energy transfer yields to (bacterio)chlorophyll acceptors. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Conformational Dynamics of the Receptor Protein Galactose/Glucose Binding Protein

    Science.gov (United States)

    Messina, Troy; Talaga, David

    2006-03-01

    We have performed time-correlated single photon counting (TCSPC) anisotropy and Stokes Shift measurements on bulk solutions of galactose/glucose binding protein. Site-directed mutagenesis was used to provide a single cysteine amino acid near the sugar-binding center of the protein (glutamine 26 to cysteine -- Q26C). The cysteine was covalently labeled with the environmentally-sensitive fluorophore acrylodan, and a long-lived ruthenium complex was covalently attached to the N-terminus to provide a fluorescent reference. The TCSPC data were analyzed using global convolute-and-compare fitting routines over the entire glucose titration and temperature range to provide minimal reduced chi-squared values and the highest time resolution possible. Using a standard ligand-binding model, the resulting distributions show that the closed (ligand-bound) conformation exists even at zero glucose concentration. At 20^oC, the relative abundance of this conformation is as high as 40%. The temperature dependence of this conformational study will be discussed and related to the ligand-binding free energy surface.

  9. Dosimetric comparison of helical tomotherapy, intensity-modulated radiation therapy, volumetric-modulated arc therapy, and 3-dimensional conformal therapy for the treatment of T1N0 glottic cancer

    International Nuclear Information System (INIS)

    Ekici, Kemal; Pepele, Eda K.; Yaprak, Bahaddin; Temelli, Oztun; Eraslan, Aysun F.; Kucuk, Nadir; Altınok, Ayse Y.; Sut, Pelin A.; Alpak, Ozlem D.; Colak, Cemil; Mayadagli, Alpaslan

    2016-01-01

    Various radiotherapy planning methods for T1N0 laryngeal cancer have been proposed to decrease normal tissue toxicity. We compare helical tomotherapy (HT), linac-based intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and 3-D conformal radiotherapy (3D-CRT) techniques for T1N0 laryngeal cancer. Overall, 10 patients with T1N0 laryngeal cancer were selected and evaluated. Furthermore, 10 radiotherapy treatment plans have been created for all 10 patients, including HT, IMRT, VMAT, and 3D-CRT. IMRT, VMAT, and HT plans vs 3D-CRT plans consistently provided superior planning target volume (PTV) coverage. Similar target coverage was observed between the 3 IMRT modalities. Compared with 3D-CRT, IMRT, HT, and VMAT significantly reduced the mean dose to the carotid arteries. VMAT resulted in the lowest mean dose to the submandibular and thyroid glands. Compared with 3D-CRT, IMRT, HT, and VMAT significantly increased the maximum dose to the spinal cord It was observed that the 3 IMRT modalities studied showed superior target coverage with less variation between each plan in comparison with 3D-CRT. The 3D-CRT plans performed better at the D max of the spinal cord. Clinical investigation is warranted to determine if these treatment approaches would translate into a reduction in radiation therapy–induced toxicities.

  10. Conformational Entropy of FK506 Binding to FKBP12 Determined by Nuclear Magnetic Resonance Relaxation and Molecular Dynamics Simulations.

    Science.gov (United States)

    Solomentsev, Gleb; Diehl, Carl; Akke, Mikael

    2018-03-06

    FKBP12 (FK506 binding protein 12 kDa) is an important drug target. Nuclear magnetic resonance (NMR) order parameters, describing amplitudes of motion on the pico- to nanosecond time scale, can provide estimates of changes in conformational entropy upon ligand binding. Here we report backbone and methyl-axis order parameters of the apo and FK506-bound forms of FKBP12, based on 15 N and 2 H NMR relaxation. Binding of FK506 to FKBP12 results in localized changes in order parameters, notably for the backbone of residues E54 and I56 and the side chains of I56, I90, and I91, all positioned in the binding site. The order parameters increase slightly upon FK506 binding, indicating an unfavorable entropic contribution to binding of TΔ S = -18 ± 2 kJ/mol at 293 K. Molecular dynamics simulations indicate a change in conformational entropy, associated with all dihedral angles, of TΔ S = -26 ± 9 kJ/mol. Both these values are significant compared to the total entropy of binding determined by isothermal titration calorimetry and referenced to a reactant concentration of 1 mM ( TΔ S = -29 ± 1 kJ/mol). Our results reveal subtle differences in the response to ligand binding compared to that of the previously studied rapamycin-FKBP12 complex, despite the high degree of structural homology between the two complexes and their nearly identical ligand-FKBP12 interactions. These results highlight the delicate dependence of protein dynamics on drug interactions, which goes beyond the view provided by static structures, and reinforce the notion that protein conformational entropy can make important contributions to the free energy of ligand binding.

  11. Real-Time Dynamic MLC Tracking for Intensity Modulated Arc Therapy

    DEFF Research Database (Denmark)

    Falk, Marianne

    Motion management of intra-fraction tumour motion during radiotherapy treatment can be a challenging task in order to achieve tumour control as well as minimizing the dose to the surrounding healthy tissue. Real-time dynamic multileaf collimator (MLC) tracking is a novel method for intra-fraction...

  12. 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...

  13. Modeling 3D Dynamic Rupture on Arbitrarily-Shaped faults by Boundary-Conforming Finite Difference Method

    Science.gov (United States)

    Zhu, D.; Zhu, H.; Luo, Y.; Chen, X.

    2008-12-01

    We use a new finite difference method (FDM) and the slip-weakening law to model the rupture dynamics of a non-planar fault embedded in a 3-D elastic media with free surface. The new FDM, based on boundary- conforming grid, sets up the mapping equations between the curvilinear coordinate and the Cartesian coordinate and transforms irregular physical space to regular computational space; it also employs a higher- order non-staggered DRP/opt MacCormack scheme which is of low dispersion and low dissipation so that the high accuracy and stability of our rupture modeling are guaranteed. Compared with the previous methods, not only we can compute the spontaneous rupture of an arbitrarily shaped fault, but also can model the influence of the surface topography on the rupture process of earthquake. In order to verify the feasibility of this method, we compared our results and other previous results, and found out they matched perfectly. Thanks to the boundary-conforming FDM, problems such as dynamic rupture with arbitrary dip, strike and rake over an arbitrary curved plane can be handled; and supershear or subshear rupture can be simulated with different parameters such as the initial stresses and the critical slip displacement Dc. Besides, our rupture modeling is economical to be implemented owing to its high efficiency and does not suffer from displacement leakage. With the help of inversion data of rupture by field observations, this method is convenient to model rupture processes and seismograms of natural earthquakes.

  14. Modification of the histone tetramer at the H3-H3 interface impacts tetrasome conformations and dynamics

    Science.gov (United States)

    Ordu, Orkide; Kremser, Leopold; Lusser, Alexandra; Dekker, Nynke H.

    2018-03-01

    Nucleosomes consisting of a short piece of deoxyribonucleic acid (DNA) wrapped around an octamer of histone proteins form the fundamental unit of chromatin in eukaryotes. Their role in DNA compaction comes with regulatory functions that impact essential genomic processes such as replication, transcription, and repair. The assembly of nucleosomes obeys a precise pathway in which tetramers of histones H3 and H4 bind to the DNA first to form tetrasomes, and two dimers of histones H2A and H2B are subsequently incorporated to complete the complex. As viable intermediates, we previously showed that tetrasomes can spontaneously flip between a left-handed and right-handed conformation of DNA-wrapping. To pinpoint the underlying mechanism, here we investigated the role of the H3-H3 interface for tetramer flexibility in the flipping process at the single-molecule level. Using freely orbiting magnetic tweezers, we studied the assembly and structural dynamics of individual tetrasomes modified at the cysteines close to this interaction interface by iodoacetamide (IA) in real time. While such modification did not affect the structural properties of the tetrasomes, it caused a 3-fold change in their flipping kinetics. The results indicate that the IA-modification enhances the conformational plasticity of tetrasomes. Our findings suggest that subnucleosomal dynamics may be employed by chromatin as an intrinsic and adjustable mechanism to regulate DNA supercoiling.

  15. 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.

  16. Dynamic conformational change regulates the protein-DNA recognition: an investigation on binding of a Y-family polymerase to its target DNA.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    2014-09-01

    Full Text Available 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.

  17. Investigation of calcium-dependent activity and conformational dynamics of zebra fish 12-lipoxygenase.

    Science.gov (United States)

    Mittal, Monica; Hasan, Mahmudul; Balagunaseelan, Navisraj; Fauland, Alexander; Wheelock, Craig; Rådmark, Olof; Haeggström, Jesper Z; Rinaldo-Matthis, Agnes

    2017-08-01

    A 12-lipoxygenase in zebra fish (zf12-LOX) was found to be required for normal embryonic development and LOXs are of great interest for targeted drug designing. In this study, we investigate the structural-functional aspects of zf12-LOX in response to calcium. A soluble version of zf12-LOX was created by mutagenesis. Based on multiple sequence alignment, we mutated the putative calcium-responsive amino acids in N-PLAT domain of soluble zf12-LOX. Using a series of biophysical methods, we ascertained the oligomeric state, stability, structural integrity and conformational changes of zf12-LOX in response to calcium. We also compared the biophysical properties of soluble zf12-LOX with the mutant in the absence and presence of calcium. Here we provide a detailed characterization of soluble zf12-LOX and the mutant. Both proteins exist as compact monomers in solution, however the enzyme activity of soluble zf12-LOX is significantly increased in presence of calcium. We find that the stimulatory effect of calcium on zf12-LOX is related to a change in protein structure as observed by SAXS, adopting an open-state. In contrast, enzyme with a mutated calcium regulatory site has reduced activity-response to calcium and restricted large re-modeling, suggesting that it retains a closed-state in response to calcium. Taken together, our study suggests that Ca 2+ -dependent regulation is associated with different domain conformation(s) that might change the accessibility to substrate-binding site in response to calcium. The study can be broadly implicated in better understanding the mode(s) of action of LOXs, and the enzymes regulated by calcium in general. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Trivial dynamics in discrete-time systems: carrying simplex and translation arcs

    Science.gov (United States)

    Niu, Lei; Ruiz-Herrera, Alfonso

    2018-06-01

    In this paper we show that the dynamical behavior in (first octant) of the classical Kolmogorov systems of competitive type admitting a carrying simplex can be sometimes determined completely by the number of fixed points on the boundary and the local behavior around them. Roughly speaking, T has trivial dynamics (i.e. the omega limit set of any orbit is a connected set contained in the set of fixed points) provided T has exactly four hyperbolic nontrivial fixed points in with local attractors on the carrying simplex and local repellers on the carrying simplex; and there exists a unique hyperbolic fixed point in Int. Our results are applied to some classical models including the Leslie–Gower models, Atkinson-Allen systems and Ricker maps.

  19. The ArcSDE GIS Dynamic Population Model Tool for Savannah River Site Emergency Response

    International Nuclear Information System (INIS)

    MCLANE, TRACY; JONES, DWIGHT

    2005-01-01

    The Savannah River Site (SRS) is a 310-square-mile Department of Energy site located near Aiken, South Carolina. With a workforce of over 10,000 employees and subcontractors, SRS emergency personnel must be able to respond to an emergency event in a timely and effective manner, in order to ensure the safety and security of the Site. Geographic Information Systems (GIS) provides the technology needed to give managers and emergency personnel the information they need to make quick and effective decisions. In the event of a site evacuation, knowing the number of on-site personnel to evacuate from a given area is an essential piece of information for emergency staff. SRS has developed a GIS Dynamic Population Model Tool to quickly communicate real-time information that summarizes employee populations by facility area and building and then generates dynamic maps that illustrate output statistics

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

    International Nuclear Information System (INIS)

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

    2017-01-01

    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.

  1. Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating.

    Science.gov (United States)

    Vullo, Sabrina; Bonifacio, Gaetano; Roy, Sophie; Johner, Niklaus; Bernèche, Simon; Kellenberger, Stephan

    2017-04-04

    Acid-sensing ion channels (ASICs) are proton-activated Na + channels expressed in the nervous system, where they are involved in learning, fear behaviors, neurodegeneration, and pain sensation. In this work, we study the role in pH sensing of two regions of the ectodomain enriched in acidic residues: the acidic pocket, which faces the outside of the protein and is the binding site of several animal toxins, and the palm, a central channel domain. Using voltage clamp fluorometry, we find that the acidic pocket undergoes conformational changes during both activation and desensitization. Concurrently, we find that, although proton sensing in the acidic pocket is not required for channel function, it does contribute to both activation and desensitization. Furthermore, protonation-mimicking mutations of acidic residues in the palm induce a dramatic acceleration of desensitization followed by the appearance of a sustained current. In summary, this work describes the roles of potential pH sensors in two extracellular domains, and it proposes a model of acidification-induced conformational changes occurring in the acidic pocket of ASIC1a.

  2. NMR studies of the solution conformation and dynamics of the tyrocidine peptide antibiotics

    International Nuclear Information System (INIS)

    Zhou, N.

    1985-01-01

    The tyrocidine B and tyrocidine C 1 H NMR spectra in DMSO-d 6 were assigned by using 2D 1 H- 1 H correlation spectroscopy and 1D double resonance experiments. Based on the proton chemical shifts, 3 J/sub NH-Nα/ coupling constants, the chemical shift temperature dependence, and 1D and 2D 1 H- 1 H NOE values, a backbone conformation consisting of an anti-parallel β-pleated sheet, a type I β-turn and a type II' β-turn was suggested for both tyrocidines B and C. Seven out of ten side chains were determined to exist predominantly in one classical Chi 1 rotamer; while the residues Val 1 and Leu 3 had two Chi 1 rotamers which were significantly populated. Chi 2 angles were determined for residues Phe 4 , Trp 6 , DPhe 7 (D Trp 7 ) and Asn 8 . The natural abundance 13 C spectra of tyrocidine B and tyrocidine C were assigned by using 1 H- 13 C correlation spectroscopy. A study of the effect of soluble paramagnetic nitroxide compounds on tyrocidine A proton T 1 values were performed which confirmed the proposed tyrocidine A conformation. It also proved that these nitroxide compounds are very useful in studying proton solvent exposure, and therefore in delineating hydrogen bonding. A proton NMR study of the opioid peptide dynorphin-(1-13) in aqueous solution was reported which was consistent with a non-ordered molecule in the solution

  3. Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    2017-09-01

    Full Text Available Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1 hyperinsulinemia may be due to the drastically reduced activity (and binding affinity of the mutant insulins. 2 Y26BS and Y26BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

  4. 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.

  5. Effects of force fields on the conformational and dynamic properties of amyloid β(1-40) dimer explored by replica exchange molecular dynamics simulations.

    Science.gov (United States)

    Watts, Charles R; Gregory, Andrew; Frisbie, Cole; Lovas, Sándor

    2018-03-01

    The conformational space and structural ensembles of amyloid beta (Aβ) peptides and their oligomers in solution are inherently disordered and proven to be challenging to study. Optimum force field selection for molecular dynamics (MD) simulations and the biophysical relevance of results are still unknown. We compared the conformational space of the Aβ(1-40) dimers by 300 ns replica exchange MD simulations at physiological temperature (310 K) using: the AMBER-ff99sb-ILDN, AMBER-ff99sb*-ILDN, AMBER-ff99sb-NMR, and CHARMM22* force fields. Statistical comparisons of simulation results to experimental data and previously published simulations utilizing the CHARMM22* and CHARMM36 force fields were performed. All force fields yield sampled ensembles of conformations with collision cross sectional areas for the dimer that are statistically significantly larger than experimental results. All force fields, with the exception of AMBER-ff99sb-ILDN (8.8 ± 6.4%) and CHARMM36 (2.7 ± 4.2%), tend to overestimate the α-helical content compared to experimental CD (5.3 ± 5.2%). Using the AMBER-ff99sb-NMR force field resulted in the greatest degree of variance (41.3 ± 12.9%). Except for the AMBER-ff99sb-NMR force field, the others tended to under estimate the expected amount of β-sheet and over estimate the amount of turn/bend/random coil conformations. All force fields, with the exception AMBER-ff99sb-NMR, reproduce a theoretically expected β-sheet-turn-β-sheet conformational motif, however, only the CHARMM22* and CHARMM36 force fields yield results compatible with collapse of the central and C-terminal hydrophobic cores from residues 17-21 and 30-36. Although analyses of essential subspace sampling showed only minor variations between force fields, secondary structures of lowest energy conformers are different. © 2017 Wiley Periodicals, Inc.

  6. 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

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

    Science.gov (United States)

    Baker, Joseph L; Biais, Nicolas; Tama, Florence

    2013-04-01

    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 stretching.

  8. 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.

  9. Insight the C-site pocket conformational changes responsible for sirtuin 2 activity using molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Sugunadevi Sakkiah

    Full Text Available Sirtuin belongs to a family of typical histone deacetylase which regulates the fundamental cellular biological processes including gene expression, genome stability, mitosis, nutrient metabolism, aging, mitochondrial function, and cell motility. Michael et. al. reported that B-site mutation (Q167A and H187A decreased the SIRT2 activity but still the structural changes were not reported. Hence, we performed 5 ns molecular dynamics (MD simulation on SIRT2 Apo-form and complexes with substrate/NAD(+ and inhibitor of wild type (WT, Q167A, and H187A. The results revealed that the assembly and disassembly of C-site induced by presence of substrate/NAD(+ and inhibitor, respectively. This assembly and disassembly was mainly due to the interaction between the substrate/NAD(+ and inhibitor and F96 and the distance between F96 and H187 which are present at the neck of the C-site. MD simulations suggest that the conformational change of L3 plays a major role in assembly and disassembly of C-site. Our current results strongly suggest that the distinct conformational change of L3 as well as the assembly and disassembly of C-site plays an important role in SIRT2 deacetylation function. Our study unveiled the structural changes of SIRT2 in presence of NAD(+ and inhibitor which should be helpful to improve the inhibitory potency of SIRT2.

  10. Concerted motions in HIV-1 TAR RNA may allow access to bound state conformations: RNA dynamics from NMR residual dipolar couplings.

    Science.gov (United States)

    Al-Hashimi, Hashim M; Gosser, Yuying; Gorin, Andrey; Hu, Weidong; Majumdar, Ananya; Patel, Dinshaw J

    2002-01-11

    Ground-state dynamics in RNA is a critical precursor for structural adaptation observed ubiquitously in protein-RNA recognition. A tertiary conformational analysis of the stem-loop structural element in the transactivation response element (TAR) from human immunodeficiency virus type 1 (HIV-I) RNA is presented using recently introduced NMR methods that rely on the measurement of residual dipolar couplings (RDC) in partially oriented systems. Order matrix analysis of RDC data provides evidence for inter-helical motions that are of amplitude 46(+/-4) degrees, of random directional character, and that are executed about an average conformation with an inter-helical angle between 44 degrees and 54 degrees. The generated ensemble of TAR conformations have different organizations of functional groups responsible for interaction with the trans-activator protein Tat, including conformations similar to the previously characterized bound-state conformation. These results demonstrate the utility of RDC-NMR for simultaneously characterizing RNA tertiary dynamics and average conformation, and indicate an avenue for TAR complex formation involving tertiary structure capture. Copyright 2001 Academic Press.

  11. Using 1H and 13C NMR chemical shifts to determine cyclic peptide conformations: a combined molecular dynamics and quantum mechanics approach.

    Science.gov (United States)

    Nguyen, Q Nhu N; Schwochert, Joshua; Tantillo, Dean J; Lokey, R Scott

    2018-05-10

    Solving conformations of cyclic peptides can provide insight into structure-activity and structure-property relationships, which can help in the design of compounds with improved bioactivity and/or ADME characteristics. The most common approaches for determining the structures of cyclic peptides are based on NMR-derived distance restraints obtained from NOESY or ROESY cross-peak intensities, and 3J-based dihedral restraints using the Karplus relationship. Unfortunately, these observables are often too weak, sparse, or degenerate to provide unequivocal, high-confidence solution structures, prompting us to investigate an alternative approach that relies only on 1H and 13C chemical shifts as experimental observables. This method, which we call conformational analysis from NMR and density-functional prediction of low-energy ensembles (CANDLE), uses molecular dynamics (MD) simulations to generate conformer families and density functional theory (DFT) calculations to predict their 1H and 13C chemical shifts. Iterative conformer searches and DFT energy calculations on a cyclic peptide-peptoid hybrid yielded Boltzmann ensembles whose predicted chemical shifts matched the experimental values better than any single conformer. For these compounds, CANDLE outperformed the classic NOE- and 3J-coupling-based approach by disambiguating similar β-turn types and also enabled the structural elucidation of the minor conformer. Through the use of chemical shifts, in conjunction with DFT and MD calculations, CANDLE can help illuminate conformational ensembles of cyclic peptides in solution.

  12. Change of conformation and internal dynamics of supercoiled DNA upon binding of Escherichia coli single-strand binding protein

    International Nuclear Information System (INIS)

    Langowski, J.; Benight, A.S.; Fujimoto, B.S.; Schurr, J.M.; Schomburg, U.

    1985-01-01

    The influence of Escherichia coli single-strand binding (SSB) protein on the conformation and internal dynamics of pBR322 and pUC8 supercoiled DNAs has been investigated by using dynamic light scattering at 632.8 and 351.1 nm and time-resolved fluorescence polarization anisotropy of intercalated ethidium. SSB protein binds to both DNAs up to a stoichiometry that is sufficient to almost completely relax the superhelical turns. Upon saturation binding, the translational diffusion coefficients (D 0 ) of both DNAs decrease by approximately 20%. Apparent diffusion coefficients (D/sub app/) obtained from dynamic light scattering display the well-known increase with K 2 (K = scattering vector), leveling off toward a plateau value (D/sub plat/) at high K 2 . For both DNAs, the difference D/sub plat/ - D 0 increases upon relaxation of supercoils by SSB protein, which indicates a corresponding enhancement of the subunit mobilities in internal motions. Fluorescence polarization anisotropy measurements on free and complexed pBR322 DNA indicate a (predominantly) uniform torsional rigidity for the saturated DNA/SSB protein complex that is significantly reduced compared to the free DNA. These observations are all consistent with the notion that binding of SSB protein is accompanied by a gradual loss of supercoils and saturates when the superhelical twist is largely removed

  13. Exploration of Protein Conformational Change with PELE and Meta-Dynamics.

    Science.gov (United States)

    Cossins, Benjamin P; Hosseini, Ali; Guallar, Victor

    2012-03-13

    Atomistic molecular simulation methods are now able to explore complex protein or protein-ligand dynamical space in a tractable way with methods such as meta-dynamics or adaptive biasing force. However, many of these methods either require a careful selection of reaction coordinates or the knowledge of an initial pathway of some kind. Thus, it is important that effective methods are developed to produce this pathway data in an efficient fashion. PELE, a proven protein-ligand sampling code, has been developed to provide rapid protein sampling in highly flexible cases, using a reduced network model eigen problem approach. The resulting method is able to rapidly sample configuration space with very general driving information. When applied to ubiquitin, PELE was able to reproduce RMSD and average force data found in molecular dynamics simulations. PELE was also applied to explore the opening/closing transition of T4 lysozyme. A meta-dynamics exploration using a low energy pathway validated that the configurations explored by PELE represent the most populated regions of phase space. PELE and meta-dynamics explorations also discovered a low free energy region where a large cross-domain helix of T4 lysozyme is broken in two. There is previous NMR evidence for the validity of this unfolded helix region.

  14. 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)...

  15. Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions

    Czech Academy of Sciences Publication Activity Database

    Dračínský, Martin; Möller, H. M.; Exner, T. E.

    2013-01-01

    Roč. 9, č. 8 (2013), s. 3806-3815 ISSN 1549-9618 R&D Projects: GA ČR GA13-24880S Institutional support: RVO:61388963 Keywords : ab initio molecular dynamics * NMR spectroscopy * DFT calculations * hydration Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.310, year: 2013

  16. Conformational dynamics of bacterial and human cytoplasmic models of the ribosomal A-site

    Czech Academy of Sciences Publication Activity Database

    Panecka, J.; Šponer, Jiří; Trylska, J.

    112C, MAY 2015 (2015), s. 96-110 ISSN 0300-9084 R&D Projects: GA ČR(CZ) GBP305/12/G034; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081707 Keywords : MOLECULAR-DYNAMICS * DECODING SITE * CRYSTAL-STRUCTURE Subject RIV: BO - Biophysics Impact factor: 3.017, year: 2015

  17. Investigation of intramolecular dynamics and conformations of α-, β- and γ-synuclein.

    Directory of Open Access Journals (Sweden)

    Vanessa C Ducas

    Full Text Available The synucleins are a family of natively unstructured proteins consisting of α-, β-, and γ-synuclein which are primarily expressed in neurons. They have been linked to a wide variety of pathologies, including neurological disorders, such as Parkinson's disease (α-synuclein and dementia with Lewy bodies (α- and β-synuclein, as well as various types of cancers (γ-synuclein. Self-association is a key pathological feature of many of these disorders, with α-synuclein having the highest propensity to form aggregates, while β-synuclein is the least prone. Here, we used a combination of fluorescence correlation spectroscopy and single molecule Förster resonance energy transfer to compare the intrinsic dynamics of different regions of all three synuclein proteins to investigate any correlation with putative functional or dysfunctional interactions. Despite a relatively high degree of sequence homology, we find that individual regions sample a broad range of diffusion coefficients, differing by almost a factor of four. At low pH, a condition that accelerates aggregation of α-synuclein, on average smaller diffusion coefficients are measured, supporting a hypothesis that slower intrachain dynamics may be correlated with self-association. Moreover, there is a surprising inverse correlation between dynamics and bulkiness of the segments. Aside from this observation, we could not discern any clear relationship between the physico-chemical properties of the constructs and their intrinsic dynamics. This work suggests that while protein dynamics may play a role in modulating self-association or interactions with other binding partners, other factors, particularly the local cellular environment, may be more important.

  18. Single-Arc IMRT?

    International Nuclear Information System (INIS)

    Bortfeld, Thomas; Webb, Steve

    2009-01-01

    The idea of delivering intensity-modulated radiation therapy (IMRT) with a multileaf collimator in a continuous dynamic mode during a single rotation of the gantry has recently gained momentum both in research and industry. In this note we investigate the potential of this Single-Arc IMRT technique at a conceptual level. We consider the original theoretical example case from Brahme et al that got the field of IMRT started. Using analytical methods, we derive deliverable intensity 'landscapes' for Single-Arc as well as standard IMRT and Tomotherapy. We find that Tomotherapy provides the greatest flexibility in shaping intensity landscapes and that it allows one to deliver IMRT in a way that comes close to the ideal case in the transverse plane. Single-Arc and standard IMRT make compromises in different areas. Only in relatively simple cases that do not require substantial intensity modulation will Single-Arc be dosimetrically comparable to Tomotherapy. Compared with standard IMRT, Single-Arc could be dosimetrically superior in certain cases if one is willing to accept the spreading of low dose values over large volumes of normal tissue. In terms of treatment planning, Single-Arc poses a more challenging optimization problem than Tomotherapy or standard IMRT. We conclude that Single-Arc holds potential as an efficient IMRT technique especially for relatively simple cases. In very complex cases, Single-Arc may unduly compromise the quality of the dose distribution, if one tries to keep the treatment time below 2 min or so. As with all IMRT techniques, it is important to explore the tradeoff between plan quality and the efficiency of its delivery carefully for each individual case. (note)

  19. 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

    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...... the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular...... 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....

  20. Myosin isoform determines the conformational dynamics and cooperativity of actin filaments in the strongly bound actomyosin complex

    Science.gov (United States)

    Prochniewicz, Ewa; Chin, Harvey F.; Henn, Arnon; Hannemann, Diane E.; Olivares, Adrian O.; Thomas, David D.; De La Cruz, Enrique M.

    2010-01-01

    SUMMARY We have used transient phosphorescence anisotropy (TPA) to detect the microsecond rotational dynamics of erythrosin iodoacetamide (ErIA)-labeled actin strongly bound to single-headed fragments of muscle myosin (muscle S1) and non-muscle myosin V (MV). The conformational dynamics of actin filaments in solution are markedly influenced by the isoform of bound myosin. Both myosins increase the final anisotropy of actin at sub-stoichiometric binding densities, indicating long-range, non-nearest neighbor cooperative restriction of filament rotational dynamics amplitude, but the cooperative unit is larger with MV than muscle S1. Both myosin isoforms also cooperatively affect the actin filament rotational correlation time, but with opposite effects; muscle S1 decreases rates of intrafilament torsional motion, while binding of MV increases the rates of motion. The cooperative effects on the rates of intrafilament motions correlate with the kinetics of myosin binding to actin filaments such that MV binds more rapidly, and muscle myosin more slowly, to partially decorated filaments than to bare filaments. The two isoforms also differ in their effects on the phosphorescence lifetime of the actin-bound ErIA; while muscle S1 increases the lifetime, suggesting decreased aqueous exposure of the probe, MV does not induce a significant change. We conclude that the dynamics and structure of actin in the strongly bound actomyosin complex is determined by the isoform of the bound myosin, in a manner likely to accommodate the diverse functional roles of actomyosin in muscle and non-muscle cells. PMID:19962990

  1. Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale

    Czech Academy of Sciences Publication Activity Database

    Islam, B.; Sgobba, M.; Laughton, C.; Orozco, M.; Šponer, Jiří; Neidle, S.; Haider, S.

    2013-01-01

    Roč. 41, č. 4 (2013), s. 2723-2735 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GAP208/11/1822 Grant - others:GA ČR(CZ) ED1.1.00/02.0068 Program:ED Institutional support: RVO:68081707 Keywords : MOLECULAR-DYNAMICS * CRYSTAL-STRUCTURE * B-DNA Subject RIV: BO - Biophysics Impact factor: 8.808, year: 2013

  2. Effects of N-glycosylation on protein conformation and dynamics: Protein Data Bank analysis and molecular dynamics simulation study.

    Science.gov (United States)

    Lee, Hui Sun; Qi, Yifei; Im, Wonpil

    2015-03-09

    N-linked glycosylation is one of the most important, chemically complex, and ubiquitous post-translational modifications in all eukaryotes. The N-glycans that are covalently linked to proteins are involved in numerous biological processes. There is considerable interest in developments of general approaches to predict the structural consequences of site-specific glycosylation and to understand how these effects can be exploited in protein design with advantageous properties. In this study, the impacts of N-glycans on protein structure and dynamics are systematically investigated using an integrated computational approach of the Protein Data Bank structure analysis and atomistic molecular dynamics simulations of glycosylated and deglycosylated proteins. Our study reveals that N-glycosylation does not induce significant changes in protein structure, but decreases protein dynamics, likely leading to an increase in protein stability. Overall, these results suggest not only a common role of glycosylation in proteins, but also a need for certain proteins to be properly glycosylated to gain their intrinsic dynamic properties.

  3. Beam shaping for conformal fractionated stereotactic radiotherapy: a modeling study

    International Nuclear Information System (INIS)

    Hacker, Fred L.; Kooy, Hanne M.; Bellerive, Marc R.; Killoran, Joseph H.; Leber, Zachary H.; Shrieve, Dennis C.; Tarbell, Nancy J.; Loeffler, Jay S.

    1997-01-01

    Purpose: The patient population treated with fractionated stereotactic radiotherapy (SRT) is significantly different than that treated with stereotactic radiosurgery (SRS). Generally, lesions treated with SRT are larger, less spherical, and located within critical regions of the central nervous system; hence, they offer new challenges to the treatment planner. Here a simple, cost effective, beam shaping system has been evaluated relative to both circular collimators and an ideal dynamically conforming system for effectiveness in providing conformal therapy for these lesions. Methods and Materials: We have modeled a simple system for conformal arc therapy using four independent jaws. The jaw positions and collimator angle are changed between arcs but held fixed for the duration of each arc. Eleven previously treated SRT cases have been replanned using this system. The rectangular jaw plans were then compared to the original treatment plans which used circular collimators. The plans were evaluated with respect to tissue sparing at 100%, 80%, 50%, and 20% of the prescription dose. A plan was also done for each tumor in which the beam aperture was continuously conformed to the beams eye view projection of the tumor. This was used as an ideal standard for conformal therapy in the absence of fluence modulation. Results: For tumors with a maximum extent of over 3.5 cm the rectangular jaw plans reduced the mean volume of healthy tissue involved at the prescription dose by 57% relative to the circular collimator plans. The ideal conformal plans offered no significant further improvement at the prescription dose. The relative advantage of the rectangular jaw plans decreased at lower isodoses so that at 20% of the prescription dose tissue involvement for the rectangular jaw plans was equivalent to that for the circular collimator plans. At these isodoses the ideal conformal plans gave substantially better tissue sparing. Conclusion: A simple and economical field shaping

  4. 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.

  5. Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB.

    Science.gov (United States)

    Colavin, Alexandre; Hsin, Jen; Huang, Kerwyn Casey

    2014-03-04

    The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent intersubunit bending, with hydrolyzed polymers favoring a straighter conformation. We use steered simulations to demonstrate a coupling between intersubunit bending and the degree of flattening of each subunit, suggesting cooperative bending along a filament. Taken together, our results provide molecular-scale insight into the diversity of structural states of MreB and the relationships among polymerization, hydrolysis, and filament properties, which may be applicable to other members of the broad actin family.

  6. Conformations of flanking bases in HIV-1 RNA DIS kissing complexes studied by molecular dynamics

    Czech Academy of Sciences Publication Activity Database

    Réblová, Kamila; Fadrná, E.; Sarzynska, J.; Kulinski, T.; Kulhánek, P.; Ennifar, E.; Koča, J.; Šponer, Jiří

    2007-01-01

    Roč. 93, č. 11 (2007), s. 3932-3949 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LC06030; GA ČR(CZ) GA203/05/0009; GA ČR(CZ) GA203/05/0388; GA AV ČR(CZ) 1QS500040581 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : molecular dynamics * RNA * virus Subject RIV: BO - Biophysics Impact factor: 4.627, year: 2007

  7. Detailed conformation dynamics and activation process of wild type c-Abl and T315I mutant

    Science.gov (United States)

    Yang, Li-Jun; Zhao, Wen-Hua; Liu, Qian

    2014-10-01

    Bcr-Abl is an important target for therapy against chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The synergistic effect between myristyl pocket and the ATP pocket has been found. But its detailed information based on molecular level still has not been achieved. In this study, conventional molecular dynamics (CMD) and target molecular dynamics (TMD) simulations were performed to explore the effect of T315I mutation on dynamics and activation process of Abl containing the N-terminal cap (Ncap). The CMD simulation results reveal the increasing flexibility of ATP pocket in kinase domain (KD) after T315I mutation which confirms the disability of ATP-pocket inhibitors to the Abl-T315I mutant. On the contrary, the T315I mutation decreased the flexibility of remote helix αI which suggests the synergistic effect between them. The mobility of farther regions containing Ncap, SH3, SH2 and SH2-KD linker were not affected by T315I mutation. The TMD simulation results show that the activation process of wild type Abl and Abl-T315I mutant experienced global conformation change. Their differences were elucidated by the activation motion of subsegments including A-loop, P-loop and Ncap. Besides, the T315I mutation caused decreasing energy barrier and increasing intermediate number in activation process, which results easier activation process. The TMD and CMD results indicate that a drug targeting only the ATP pocket is not enough to inhibit the Abl-T315I mutant. An effective way to inhibit the abnormal activity of Abl-T315I mutant is to combine the ATP-pocket inhibitors with inhibitors binding at non-ATP pockets mainly related to Ncap, SH2-KD linker and myristyl pocket.

  8. 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.

  9. 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.

  10. "Invisible" conformers of an antifungal disulfide protein revealed by constrained cold and heat unfolding, CEST-NMR experiments, and molecular dynamics calculations.

    Science.gov (United States)

    Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

    2015-03-23

    Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20-40 % at 298 K in a disulfide-rich protein. In addition, sensitive (15) N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR "dark matter". Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  11. “Invisible” Conformers of an Antifungal Disulfide Protein Revealed by Constrained Cold and Heat Unfolding, CEST-NMR Experiments, and Molecular Dynamics Calculations

    Science.gov (United States)

    Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

    2015-01-01

    Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20–40 % at 298 K in a disulfide-rich protein. In addition, sensitive 15N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR “dark matter”. Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. PMID:25676351

  12. Conformational dynamics of Rouse chains during creep/recovery processes: a review

    International Nuclear Information System (INIS)

    Watanabe, Hiroshi; Inoue, Tadashi

    2005-01-01

    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. Conformational sampling enhancement of replica exchange molecular dynamics simulations using swarm particle intelligence

    International Nuclear Information System (INIS)

    Kamberaj, Hiqmet

    2015-01-01

    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

  14. Consolidating NASA's Arc Jets

    Science.gov (United States)

    Balboni, John A.; Gokcen, Tahir; Hui, Frank C. L.; Graube, Peter; Morrissey, Patricia; Lewis, Ronald

    2015-01-01

    The paper describes the consolidation of NASA's high powered arc-jet testing at a single location. The existing plasma arc-jet wind tunnels located at the Johnson Space Center were relocated to Ames Research Center while maintaining NASA's technical capability to ground-test thermal protection system materials under simulated atmospheric entry convective heating. The testing conditions at JSC were reproduced and successfully demonstrated at ARC through close collaboration between the two centers. New equipment was installed at Ames to provide test gases of pure nitrogen mixed with pure oxygen, and for future nitrogen-carbon dioxide mixtures. A new control system was custom designed, installed and tested. Tests demonstrated the capability of the 10 MW constricted-segmented arc heater at Ames meets the requirements of the major customer, NASA's Orion program. Solutions from an advanced computational fluid dynamics code were used to aid in characterizing the properties of the plasma stream and the surface environment on the calorimeters in the supersonic flow stream produced by the arc heater.

  15. Conformational dynamics and ligand binding in the multi-domain protein PDC109.

    Directory of Open Access Journals (Sweden)

    Hyun Jin Kim

    2010-02-01

    Full Text Available PDC109 is a modular multi-domain protein with two fibronectin type II (Fn2 repeats joined by a linker. It plays a major role in bull sperm binding to the oviductal epithelium through its interactions with phosphorylcholines (PhCs, a head group of sperm cell membrane lipids. The crystal structure of the PDC109-PhC complex shows that each PhC binds to the corresponding Fn2 domain, while the two domains are on the same face of the protein. Long timescale explicit solvent molecular dynamics (MD simulations of PDC109, in the presence and absence of PhC, suggest that PhC binding strongly correlates with the relative orientation of choline-phospholipid binding sites of the two Fn2 domains; unless the two domains tightly bind PhCs, they tend to change their relative orientation by deforming the flexible linker. The effective PDC109-PhC association constant of 28 M(-1, estimated from their potential of mean force is consistent with the experimental result. Principal component analysis of the long timescale MD simulations was compared to the significantly less expensive normal mode analysis of minimized structures. The comparison indicates that difference between relative domain motions of PDC109 with bound and unbound PhC is captured by the first principal component in the principal component analysis as well as the three lowest normal modes in the normal mode analysis. The present study illustrates the use of detailed MD simulations to clarify the energetics of specific ligand-domain interactions revealed by a static crystallographic model, as well as their influence on relative domain motions in a multi-domain protein.

  16. Volumetric modulated arc therapy: IMRT in a single gantry arc

    International Nuclear Information System (INIS)

    Otto, Karl

    2008-01-01

    In this work a novel plan optimization platform is presented where treatment is delivered efficiently and accurately in a single dynamically modulated arc. Improvements in patient care achieved through image-guided positioning and plan adaptation have resulted in an increase in overall treatment times. Intensity-modulated radiation therapy (IMRT) has also increased treatment time by requiring a larger number of beam directions, increased monitor units (MU), and, in the case of tomotherapy, a slice-by-slice delivery. In order to maintain a similar level of patient throughput it will be necessary to increase the efficiency of treatment delivery. The solution proposed here is a novel aperture-based algorithm for treatment plan optimization where dose is delivered during a single gantry arc of up to 360 deg. The technique is similar to tomotherapy in that a full 360 deg. of beam directions are available for optimization but is fundamentally different in that the entire dose volume is delivered in a single source rotation. The new technique is referred to as volumetric modulated arc therapy (VMAT). Multileaf collimator (MLC) leaf motion and number of MU per degree of gantry rotation is restricted during the optimization so that gantry rotation speed, leaf translation speed, and dose rate maxima do not excessively limit the delivery efficiency. During planning, investigators model continuous gantry motion by a coarse sampling of static gantry positions and fluence maps or MLC aperture shapes. The technique presented here is unique in that gantry and MLC position sampling is progressively increased throughout the optimization. Using the full gantry range will theoretically provide increased flexibility in generating highly conformal treatment plans. In practice, the additional flexibility is somewhat negated by the additional constraints placed on the amount of MLC leaf motion between gantry samples. A series of studies are performed that characterize the relationship

  17. Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

    Science.gov (United States)

    Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

    2017-07-01

    Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

  18. 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.

  19. Femtosecond Heterodyne Transient Grating Detection of Conformational Dynamics in the S0 (11Ag-) State of Carotenoids After Nonradiative Decay of the S2 (11Bu+) State

    Science.gov (United States)

    Roscioli, Jerome D.; Ghosh, Soumen; Bishop, Michael M.; Lafountain, Amy M.; Frank, Harry A.; Beck, Warren F.

    Transient grating spectroscopy was used to study the dynamics of nonradiative decay of the S1 (21Ag-) state in ß-carotene and peridinin after optical preparation of the S2) state. The kinetics of the recovery of the absorption and dispersion components of the third-order signal exhibit significantly different time constants. For β-carotene in benzonitrile, the absorption and dispersion recovery time constants are 11.6 and 10.2 ps. For peridinin in methanol, the time constants are 9.9 and 7.4 ps. These results indicate that the initial product of the decay of the S1 state is a conformationally displaced structure. The decay rate for the S1 state and the conformational relaxation rate are both slowed in peridinin as the polarity of the solvent decreases; in ethyl acetate, the conformational relaxation time constant is 45 ps, which rules out a dominant contribution from vibrational cooling. These results indicate that the S1 state develops intramolecular charge transfer character owing to distortions along torsional and out-of-plane coordinates, with a pyramidal structure favored as the most stable conformation. Recovery of the photoselected ground state conformation involves a reverse charge-transfer event followed by relaxation to a planar structure. Work supported by Photosynthetic Systems Program of the U.S. Department of Energy under Grant DE-SC0010847.

  20. Conformation and dynamics of nucleotides in bulges and symmetric internal loops in duplex DNA studied by EPR and fluorescence spectroscopies

    International Nuclear Information System (INIS)

    Cekan, Pavol; Sigurdsson, Snorri Th.

    2012-01-01

    Highlights: ► Bulges and loops were studied by both EPR and fluorescence spectroscopies using the probe Ç/Ç f . ► One-base bulge was in a temperature-dependent equilibrium between looped-out and stacked states. ► Bases in two- and three-base bulges were stacked at all temperatures, resulting in DNA bending. ► Bases were stacked in symmetrical two- to five-base internal loops, according to EPR data. ► Unexpectedly high fluorescence for the smaller loops indicated local structural perturbations. -- Abstract: The dynamics and conformation of base bulges and internal loops in duplex DNA were studied using the bifunctional spectroscopic probe Ç, which becomes fluorescent (Ç f ) upon reduction of the nitroxide functional group, along with EPR and fluorescence spectroscopies. A one-base bulge was in a conformational equilibrium between looped-out and stacked states, the former favored at higher temperature and the latter at lower temperature. Stacking of bulge bases was favored in two- and three-base bulges, independent of temperature, resulting in DNA bending as evidenced by increased fluorescence of Ç f . EPR spectra of Ç-labeled three-, four- and five-base symmetrical interior DNA bulges at 20 °C showed low mobility, indicating that the spin-label was stacked within the loop. The spin-label mobility at 37 °C increased as the loops became larger. A considerable variation in fluorescence between different loops was observed, as well as a temperature-dependence within constructs. Fluorescence unexpectedly increased as the size of the loop decreased at 2 °C. Fluorescence of the smallest loops, where a single T·T mismatch was located between the stem region and the probe, was even larger than for the single strand, indicating a considerable local structural deformation of these loops from regular B-DNA. These results show the value of combining EPR and fluorescence spectroscopy to study non-helical regions of nucleic acids.

  1. Conformational changes in a hyperthermostable glycoside hydrolase: enzymatic activity is a consequence of the loop dynamics and protonation balance.

    Directory of Open Access Journals (Sweden)

    Leandro C de Oliveira

    Full Text Available Endo-β-1, 4-mannanase from Thermotoga petrophila (TpMan is a modular hyperthermostable enzyme involved in the degradation of mannan-containing polysaccharides. The degradation of these polysaccharides represents a key step for several industrial applications. Here, as part of a continuing investigation of TpMan, the region corresponding to the GH5 domain (TpManGH5 was characterized as a function of pH and temperature. The results indicated that the enzymatic activity of the TpManGH5 is pH-dependent, with its optimum activity occurring at pH 6. At pH 8, the studies demonstrated that TpManGH5 is a molecule with a nearly spherical tightly packed core displaying negligible flexibility in solution, and with size and shape very similar to crystal structure. However, TpManGH5 experiences an increase in radius of gyration in acidic conditions suggesting expansion of the molecule. Furthermore, at acidic pH values, TpManGH5 showed a less globular shape, probably due to a loop region slightly more expanded and flexible in solution (residues Y88 to A105. In addition, molecular dynamics simulations indicated that conformational changes caused by pH variation did not change the core of the TpManGH5, which means that only the above mentioned loop region presents high degree of fluctuations. The results also suggested that conformational changes of the loop region may facilitate polysaccharide and enzyme interaction. Finally, at pH 6 the results indicated that TpManGH5 is slightly more flexible at 65°C when compared to the same enzyme at 20°C. The biophysical characterization presented here is well correlated with the enzymatic activity and provide new insight into the structural basis for the temperature and pH-dependent activity of the TpManGH5. Also, the data suggest a loop region that provides a starting point for a rational design of biotechnological desired features.

  2. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    International Nuclear Information System (INIS)

    Dai, Jin; He, Jianfeng; Niemi, Antti J.

    2016-01-01

    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.

  3. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Jin; He, Jianfeng, E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Niemi, Antti J., E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Department of Physics and Astronomy, Uppsala University, P.O. Box 803, S-75108 Uppsala (Sweden); Laboratoire de Mathematiques et Physique Theorique CNRS UMR 6083, Fédération Denis Poisson, Université de Tours, Parc de Grandmont, F37200 Tours (France)

    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.

  4. Aperture modulated arc therapy

    International Nuclear Information System (INIS)

    Crooks, S M; Wu, Xiaodong; Takita, C; Watzich, M; Xing Lei

    2003-01-01

    We show that it is possible to translate an intensity modulated radiation therapy (IMRT) treatment plan and deliver it as a single arc. This technique is referred to in this paper as aperture modulation arc therapy (AMAT). During this arc, the MLC leaves do not conform to the projection of the target PTV and the machine output of the accelerator has a constant value. Dose was calculated using the CORVUS 4.0 IMRT system, which uses a pencil beam dose algorithm, and treatments were delivered using a Varian 2100C/D Clinac. Results are presented for a head and neck and a prostate case, showing the equivalence of the IMRT and the translated AMAT delivery. For a prostate AMAT delivery, coronal plane film dose for the IMRT and AMAT deliveries agreed within 7.19 ± 6.62%. For a meningioma the coronal plane dose distributions were similar to a value of 4.6 ± 6.62%. Dose to the isocentre was measured as being within 2% of the planned value in both cases

  5. Quantitative conformational analysis of the core region of N-glycans using residual dipolar couplings, aqueous molecular dynamics, and steric alignment

    International Nuclear Information System (INIS)

    Almond, Andrew; Duus, Jens O.

    2001-01-01

    A method is described for quantitatively investigating the dynamic conformation of small oligosaccharides containing an α(1 → 6) linkage. It was applied to the oligosaccharide Man-α(1 → 3) {Man-α (1 → 6)}Man-α-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 α(1 → 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 α(1 → 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 α(1 → 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

  6. Conformational analysis of GT1B ganglioside and its interaction with botulinum neurotoxin type B: a study by molecular modeling and molecular dynamics.

    Science.gov (United States)

    Venkateshwari, Sureshkumar; Veluraja, Kasinadar

    2012-01-01

    The conformational property of oligosaccharide GT1B in aqueous environment was studied by molecular dynamics (MD) simulation using all-atom model. Based on the trajectory analysis, three prominent conformational models were proposed for GT1B. Direct and water-mediated hydrogen bonding interactions stabilize these structures. The molecular modeling and 15 ns MD simulation of the Botulinum Neuro Toxin/B (BoNT/B) - GT1B complex revealed that BoNT/B can accommodate the GT1B in the single binding mode. Least mobility was seen for oligo-GT1B in the binding pocket. The bound conformation of GT1B obtained from the MD simulation of the BoNT/B-GT1B complex bear a close conformational similarity with the crystal structure of BoNT/A-GT1B complex. The mobility noticed for Arg 1268 in the dynamics was accounted for its favorable interaction with terminal NeuNAc. The internal NeuNAc1 tends to form 10 hydrogen bonds with BoNT/B, hence specifying this particular site as a crucial space for the therapeutic design that can restrict the pathogenic activity of BoNT/B.

  7. Conformational exchange in pseudoazurin: different kinds of microsecond to millisecond dynamics characterized by their pH and buffer dependence using 15N NMR relaxation.

    Science.gov (United States)

    Hass, Mathias A S; Vlasie, Monica D; Ubbink, Marcellus; Led, Jens J

    2009-01-13

    The dynamics of the reduced form of the blue copper protein pseudoazurin from Alcaligenes faecalis S-6 was investigated using (15)N relaxation measurements with a focus on the dynamics of the micro- to millisecond time scale. Different types of conformational exchange processes are observed in the protein on this time scale. At low pH, the protonation of the C-terminal copper-ligated histidine, His81, is observed. A comparison of the exchange rates in the presence and absence of added buffers shows that the protonation is the rate-limiting step at low buffer concentrations. This finding agrees with previous observations for other blue copper proteins, e.g., amicyanin and plastocyanin. However, in contrast to plastocyanin but similar to amicyanin, a second conformational exchange between different conformations of the protonated copper site is observed at low pH, most likely triggered by the protonation of His81. This process has been further characterized using CPMG dispersion methods and is found to occur with a rate of a few thousands per second. Finally, micro- to millisecond motions are observed in one of the loop regions and in the alpha-helical regions. These motions are unaffected by pH and are unrelated to the conformational changes in the active site of pseudoazurin.

  8. SU-F-T-531: Determination of Site-Specific Dynamic-Jaw Versus Static-Jaw RapidArc Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Tien, C [Community Hospital, Munster, IN (United States); Brewer, M [Franciscan St Margaret Health, Hammond, IN (United States); Studenski, M [University of Miami, Miami, FL (United States)

    2016-06-15

    Purpose: Dynamic-jaw tracking maximizes the area blocked by both jaw and MLC in RapidArc. We developed a method to quantify jaw tracking. Methods: An Eclipse Scripting API (ESAPI) was used to export beam parameters for each arc’s control points. The specific beam parameters extracted were: gantry angle, control point number, meterset, x-jaw positions, y-jaw positions, MLC bank-number, MLC leaf-number, and MLC leaf-position. Each arc contained 178 control points with 120 MLC positions. MATLAB routines were written to process these parameters in order to calculate both the beam aperture (unblocked) size for each control point. An average aperture size was weighted by meterset. Jaw factor was defined as the ratio between dynamic-jaw to static-jaw aperture size. Jaw factor was determined for forty retrospectively replanned patients treated with static-jaw delivery sites including lung, brain, prostate, H&N, rectum, and bladder. Results: Most patients had multiple arcs and reduced-field boosts, resulting in 151 fields. Of these, the lowest (0.4722) and highest (0.9622) jaw factor was observed in prostate and rectal cases, respectively. The median jaw factor was 0.7917 meaning there is the potential unincreased blocking by 20%. Clinically, the dynamic-jaw tracking represents an area surrounding the target which would receive MLC-only leakage transmission of 1.68% versus 0.1% with jaws. Jaw-tracking was more pronounced at areas farther from the target. In prostate patients, the rectum and bladder had 5.5% and 6.3% lower mean dose, respectively; the structures closer to the prostate such as the rectum and bladder both had 1.4% lower mean dose. Conclusion: A custom ESAPI script was coupled with a MATLAB routine in order to extract beam parameters from static-jaw plans and their replanned dynamic-jaw deliveries. The effects were quantified using jaw factor which is the ratio between the meterset weighted aperture size for dynamic-jaw fields versus static-jaw fields.

  9. A constitutively activating mutation alters the dynamics and energetics of a key conformational change in a ligand-free G protein-coupled receptor.

    Science.gov (United States)

    Tsukamoto, Hisao; Farrens, David L

    2013-09-27

    G protein-coupled receptors (GPCRs) undergo dynamic transitions between active and inactive conformations. Usually, these conversions are triggered when the receptor detects an external signal, but some so-called constitutively activating mutations, or CAMs, induce a GPCR to bind and activate G proteins in the absence of external stimulation, in ways still not fully understood. Here, we investigated how a CAM alters the structure of a GPCR and the dynamics involved as the receptor transitions between different conformations. Our approach used site-directed fluorescence labeling (SDFL) spectroscopy to compare opsin, the ligand-free form of the GPCR rhodopsin, with opsin containing the CAM M257Y, focusing specifically on key movements that occur in the sixth transmembrane helix (TM6) during GPCR activation. The site-directed fluorescence labeling data indicate opsin is constrained to an inactive conformation both in detergent micelles and lipid membranes, but when it contains the M257Y CAM, opsin is more dynamic and can interact with a G protein mimetic. Further study of these receptors using tryptophan-induced quenching (TrIQ) methods indicates that in detergent, the CAM significantly increases the population of receptors in the active state, but not in lipids. Subsequent Arrhenius analysis of the TrIQ data suggests that, both in detergent and lipids, the CAM lowers the energy barrier for TM6 movement, a key transition required for conversion between the inactive and active conformations. Together, these data suggest that the lowered energy barrier is a primary effect of the CAM on the receptor dynamics and energetics.

  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

    2004-09-08

    Time series analysis is applied on the collective coordinates obtained from principal component analysis of independent molecular dynamics simulations of alpha-amylase inhibitor tendamistat and immunity protein of colicin E7 based on the Calpha 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 alpha-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 alpha-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. Copyright 2004 American Institute of Physics

  11. Conformal sequestering simplified

    International Nuclear Information System (INIS)

    Schmaltz, Martin; Sundrum, Raman

    2006-01-01

    Sequestering is important for obtaining flavor-universal soft masses in models where supersymmetry breaking is mediated at high scales. We construct a simple and robust class of hidden sector models which sequester themselves from the visible sector due to strong and conformally invariant hidden dynamics. Masses for hidden matter eventually break the conformal symmetry and lead to supersymmetry breaking by the mechanism recently discovered by Intriligator, Seiberg and Shih. We give a unified treatment of subtleties due to global symmetries of the CFT. There is enough review for the paper to constitute a self-contained account of conformal sequestering

  12. Insight into microtubule destabilization mechanism of 3,4,5-trimethoxyphenyl indanone derivatives using molecular dynamics simulation and conformational modes analysis

    Science.gov (United States)

    Tripathi, Shubhandra; Srivastava, Gaurava; Singh, Aastha; Prakasham, A. P.; Negi, Arvind S.; Sharma, Ashok

    2018-03-01

    Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αβ-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.

  13. A Method for Extracting the Free Energy Surface and Conformational Dynamics of Fast-Folding Proteins from Single Molecule Photon Trajectories

    Science.gov (United States)

    2015-01-01

    Single molecule fluorescence spectroscopy holds the promise of providing direct measurements of protein folding free energy landscapes and conformational motions. However, fulfilling this promise has been prevented by technical limitations, most notably, the difficulty in analyzing the small packets of photons per millisecond that are typically recorded from individual biomolecules. Such limitation impairs the ability to accurately determine conformational distributions and resolve sub-millisecond processes. Here we develop an analytical procedure for extracting the conformational distribution and dynamics of fast-folding proteins directly from time-stamped photon arrival trajectories produced by single molecule FRET experiments. Our procedure combines the maximum likelihood analysis originally developed by Gopich and Szabo with a statistical mechanical model that describes protein folding as diffusion on a one-dimensional free energy surface. Using stochastic kinetic simulations, we thoroughly tested the performance of the method in identifying diverse fast-folding scenarios, ranging from two-state to one-state downhill folding, as a function of relevant experimental variables such as photon count rate, amount of input data, and background noise. The tests demonstrate that the analysis can accurately retrieve the original one-dimensional free energy surface and microsecond folding dynamics in spite of the sub-megahertz photon count rates and significant background noise levels of current single molecule fluorescence experiments. Therefore, our approach provides a powerful tool for the quantitative analysis of single molecule FRET experiments of fast protein folding that is also potentially extensible to the analysis of any other biomolecular process governed by sub-millisecond conformational dynamics. PMID:25988351

  14. 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

  15. Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

    Science.gov (United States)

    Sullivan, David C; Lim, Carmay

    2006-08-24

    Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

  16. Molecular Dynamics Simulations and Classical Multidimensional Scaling Unveil New Metastable States in the Conformational Landscape of CDK2.

    Directory of Open Access Journals (Sweden)

    Pasquale Pisani

    Full Text Available Protein kinases are key regulatory nodes in cellular networks and their function has been shown to be intimately coupled with their structural flexibility. However, understanding the key structural mechanisms of large conformational transitions remains a difficult task. CDK2 is a crucial regulator of cell cycle. Its activity is finely tuned by Cyclin E/A and the catalytic segment phosphorylation, whereas its deregulation occurs in many types of cancer. ATP competitive inhibitors have failed to be approved for clinical use due to toxicity issues raised by a lack of selectivity. However, in the last few years type III allosteric inhibitors have emerged as an alternative strategy to selectively modulate CDK2 activity. In this study we have investigated the conformational variability of CDK2. A low dimensional conformational landscape of CDK2 was modeled using classical multidimensional scaling on a set of 255 crystal structures. Microsecond-scale plain and accelerated MD simulations were used to populate this landscape by using an out-of-sample extension of multidimensional scaling. CDK2 was simulated in the apo-form and in complex with the allosteric inhibitor 8-anilino-1-napthalenesulfonic acid (ANS. The apo-CDK2 landscape analysis showed a conformational equilibrium between an Src-like inactive conformation and an active-like form. These two states are separated by different metastable states that share hybrid structural features with both forms of the kinase. In contrast, the CDK2/ANS complex landscape is compatible with a conformational selection picture where the binding of ANS in proximity of the αC helix causes a population shift toward the inactive conformation. Interestingly, the new metastable states could enlarge the pool of candidate structures for the development of selective allosteric CDK2 inhibitors. The method here presented should not be limited to the CDK2 case but could be used to systematically unmask similar mechanisms

  17. 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.

  18. Clustering of arc volcanoes caused by temperature perturbations in the back-arc mantle.

    Science.gov (United States)

    Lee, Changyeol; Wada, Ikuko

    2017-06-29

    Clustering of arc volcanoes in subduction zones indicates along-arc variation in the physical condition of the underlying mantle where majority of arc magmas are generated. The sub-arc mantle is brought in from the back-arc largely by slab-driven mantle wedge flow. Dynamic processes in the back-arc, such as small-scale mantle convection, are likely to cause lateral variations in the back-arc mantle temperature. Here we use a simple three-dimensional numerical model to quantify the effects of back-arc temperature perturbations on the mantle wedge flow pattern and sub-arc mantle temperature. Our model calculations show that relatively small temperature perturbations in the back-arc result in vigorous inflow of hotter mantle and subdued inflow of colder mantle beneath the arc due to the temperature dependence of the mantle viscosity. This causes a three-dimensional mantle flow pattern that amplifies the along-arc variations in the sub-arc mantle temperature, providing a simple mechanism for volcano clustering.

  19. Effects of glycosylation on the conformation and dynamics of O-linked glycoproteins: Carbon-13 NMR studies of ovine submaxillary mucin

    International Nuclear Information System (INIS)

    Gerken, T.A.; Butenhof, K.J.; Shogren, R.

    1989-01-01

    Carbon-13 NMR spectroscopic studies of native and sequentially deglycosylated ovine submaxillary mucin (OSM) have been performed to examine the effects of glycosylation on the conformation and dynamics of the peptide core of O-linked glycoproteins. OSM is a large nonglobular glycoprotein in which nearly one-third of the amino acid residues are Ser and Thr which are glycosylated by the α-Neu-NAc(2-6)α-Ga1NAc- disaccharide. The β-carbon resonances of glycosylated Ser and Thr residues in intact and asialo mucin display considerable chemical shift heterogeneity which, upon the complete removal of carbohydrate, coalesces to single sharp resonances. This chemical shift heterogeneity is due to peptide sequence variability and is proposed to reflect the presence of sequence-dependent conformations of the peptide core. These different conformations are thought to be determined by steric interactions of the Ga1NAc residue with adjacent peptide residues. The absence of chemical shift heterogeneity in apo mucin is taken to indicate a loss in the peptide-carbohydrate steric interactions, consistent with a more relaxed random coiled structure. On the basis of the 13 C relaxation behavior the dynamics of the α-carbons appear to be unique to each amino acid type and glycosylation state. These results are consistent with the changes in molecular dimensions determined by light-scattering techniques for the same series of modified mucins. Taken together, these results further demonstrate that mucins possess a highly expanded conformation that is dominated by steric interactions between the peptide core and the O-linked Ga1NAc residue

  20. Molecular dynamics simulations of site point mutations in the TPR domain of cyclophilin 40 identify conformational states with distinct dynamic and enzymatic properties

    Science.gov (United States)

    Gur, Mert; Blackburn, Elizabeth A.; Ning, Jia; Narayan, Vikram; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Erman, Burak

    2018-04-01

    Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90). Its structure comprises an N-terminal cyclophilin domain and a C-terminal tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes residues Lys227 and Lys308, referred to as the carboxylate clamp, and is essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations, K227A and K308A, and their combinative mutant was investigated by performing a total of 5.76 μs of all-atom molecular dynamics (MD) simulations in explicit solvent. All simulations, except the K308A mutant, were found to adopt two distinct (extended or compact) conformers defined by different cyclophilin-TPR interdomain distances. The K308A mutant was only observed in the extended form which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and combined mutant also showed bimodal distributions. The experimental melting temperature, Tm, values of the mutants correlate with the degree of compactness with the K308A extended mutant having a marginally lower melting temperature. Another novel measure of compactness determined from the MD data, the "coordination shell volume," also shows a direct correlation with Tm. In addition, the MD simulations show an allosteric effect with the mutations in the remote TPR domain having a pronounced effect on the molecular motions of the enzymatic cyclophilin domain which helps rationalise the experimentally observed increase in enzyme activity measured for all three mutations.

  1. Comparing Arc-shaped Feet and Rigid Ankles with Flat Feet and Compliant Ankles for a Dynamic Walker

    DEFF Research Database (Denmark)

    Kuhlemann, Ilyas; Matthias Braun, Jan; Wörgötter, Florentin

    2014-01-01

    In this paper we show that exchanging curved feet and rigid ankles by at feet and compliant ankles improves the range of gait parameters for a bipedal dynamic walker. The new lower legs were designed such that they t to the old set-up, allowing for a direct and quantitative comparison. The dynamic...

  2. 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.

  3. 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

  4. 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.

  5. Conformal Infinity.

    Science.gov (United States)

    Frauendiener, Jörg

    2004-01-01

    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.

  6. 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.

  7. 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.

  8. Conformal Infinity

    OpenAIRE

    Frauendiener, J?rg

    2000-01-01

    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...

  9. Arc saw development report

    International Nuclear Information System (INIS)

    Deichelbohrer, P.R.; Beitel, G.A.

    1981-01-01

    The arc saw is one of the key components of the Contaminated Equipment Volume Reduction (CEVR) Program. This report describes the progress of the arc saw from its inception to its current developmental status. History of the arc saw and early contributors are discussed. Particular features of the arc saw and their advantages for CEVR are detailed. Development of the arc saw including theory of operation, pertinent experimental results, plans for the large arc saw and advanced control systems are covered. Associated topics such as potential applications for the arc saw and other arc saw installations in the world is also touched upon

  10. 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.

  11. Irradiated dynamic fracture toughness of ASTM A533, Grade B, Class 1 steel plate and submerged arc weldment. Heavy section steel technology program technical report No. 41

    International Nuclear Information System (INIS)

    Davidson, J.A.; Ceschini, L.J.; Shogan, R.P.; Rao, G.V.

    1976-10-01

    As a result of the Heavy Section Steel Technology Program (HSST), sponsored by the Nuclear Regulatory Commission, Westinghouse Electric Corporation conducted dynamic fracture toughness tests on irradiated HSST Plate 02 and submerged arc weldment material. Testing performed at the Westinghouse Research and Development Laboratory in Pittsburgh, Pennsylvania, included 0.394T compact tension, 1.9T compact tension, and 4T compact tension specimens. This data showed that, in the transition region, dynamic test procedures resulted in lower (compared to static) fracture toughness results, and that weak direction (WR) oriented specimen data were lower than the strong direction (RW) oriented specimen results. Irradiated lower-bound fracture toughness results of the HSST Program material were well above the adjusted ASME Section III K/sub IR/ curve. An irradiated and nonirradiated 4T-CT specimen was tested during a fracture toughness test as a preliminary study to determine the effect of irradiation on the acoustic emission-stress intensity factor relation in pressure vessel grade steel. The results indicated higher levels of acoustic emission activity from the irradiated sample as compared to the unirradiated one at a given stress intensity factor (K) level

  12. Bifurcation theory of ac electric arcing

    International Nuclear Information System (INIS)

    Christen, Thomas; Peinke, Emanuel

    2012-01-01

    The performance of alternating current (ac) electric arcing devices is related to arc extinction or its re-ignition at zero crossings of the current (so-called ‘current zero’, CZ). Theoretical investigations thus usually focus on the transient behaviour of arcs near CZ, e.g. by solving the modelling differential equations in the vicinity of CZ. This paper proposes as an alternative approach to investigate global mathematical properties of the underlying periodically driven dynamic system describing the electric circuit containing the arcing device. For instance, the uniqueness of the trivial solution associated with the insulating state indicates the extinction of any arc. The existence of non-trivial attractors (typically a time-periodic state) points to a re-ignition of certain arcs. The performance regions of arcing devices, such as circuit breakers and arc torches, can thus be identified with the regions of absence and existence, respectively, of non-trivial attractors. Most important for applications, the boundary of a performance region in the model parameter space is then associated with the bifurcation of the non-trivial attractors. The concept is illustrated for simple black-box arc models, such as the Mayr and the Cassie model, by calculating for various cases the performance boundaries associated with the bifurcation of ac arcs. (paper)

  13. Proposition of a modification to the VAR process and its application in the consolidation of pressed zircaloy chips and the evaluation of the dynamical system of the electric arc

    International Nuclear Information System (INIS)

    Mucsi, Cristiano Stefano

    2005-01-01

    The objective of this work is the investigation of a new process as an alternative to the Vacuum Arc Remelting technology in the consolidation of Zircaloy chips. A procedure is proposed for the recycling of primary Zircaloy scraps by means of a modified VAR furnace. The performed studies were made in order to optimise the low cost new devices added to existing VAR furnace prototype, find ideal operational conditions, evaluate data acquisition system and the electric arc dynamical system in order to made viable the automated control of the modified VAR prototype. A funnel-crucible special device was developed and installed in a VAR prototype furnace allowing ingots to be obtained from pressed chips. This indicated the viability of creation of a new process for the consolidation of Zircaloy chips. The voltage of the electric arc during the melting runs was digitally recorded allowing the evaluation of the electric arc dynamics by using the topological invariant of the system: correlation dimension and the higher Liapunov exponent. (author)

  14. TH-C-12A-09: Planning and Delivery of the Fully Dynamic Trajectory Modulated Arc Therapy: Application to Accelerated Partial Breast Irradiation

    International Nuclear Information System (INIS)

    Liang, J; Atwood, T; Fahimian, B; Chin, E; Hristov, D; Otto, K

    2014-01-01

    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

  15. 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

  16. Steady states in conformal theories

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    A novel conjecture regarding the steady state behavior of conformal field theories placed between two heat baths will be presented. Some verification of the conjecture will be provided in the context of fluid dynamics and holography.

  17. Practical considerations for investigation of protein conformational dynamics by {sup 15}N R{sub 1ρ} relaxation dispersion

    Energy Technology Data Exchange (ETDEWEB)

    Walinda, Erik [Kyoto University, Department of Molecular and Cellular Physiology, Graduate School of Medicine (Japan); Morimoto, Daichi; Shirakawa, Masahiro; Sugase, Kenji, E-mail: sugase@moleng.kyoto-u.ac.jp [Kyoto University, Department of Molecular Engineering, Graduate School of Engineering (Japan)

    2017-03-15

    It is becoming increasingly apparent that proteins are not static entities and that their function often critically depends on accurate sampling of multiple conformational states in aqueous solution. Accordingly, the development of methods to study conformational states in proteins beyond their ground-state structure (“excited states”) has crucial biophysical importance. Here we investigate experimental schemes for optimally probing chemical exchange processes in proteins on the micro- to millisecond timescale by {sup 15}N R{sub 1ρ} relaxation dispersion. The schemes use selective Hartmann–Hahn cross-polarization (CP) transfer for excitation, and derive peak integrals from 1D NMR spectra (Korzhnev et al. in J Am Chem Soc 127:713–721, 2005; Hansen et al. in J Am Chem Soc 131:3818–3819, 2009). Simulation and experiment collectively show that in such CP-based schemes care has to be taken to achieve accurate suppression of undesired off-resonance coherences, when using weak spin-lock fields. This then (i) ensures that relaxation dispersion profiles in the absence of chemical exchange are flat, and (ii) facilitates extraction of relaxation dispersion profiles in crowded regions of the spectrum. Further improvement in the quality of the experimental data is achieved by recording the free-induction decays in an interleaved manner and including a heating-compensation element. The reported considerations will particularly benefit the use of CP-based R{sub 1ρ} relaxation dispersion to analyze conformational exchange processes in larger proteins, where resonance line overlap becomes the main limiting factor.

  18. NMR studies of differences in the conformations and dynamics of ligand complexes formed with mutant dihydrofolate reductases

    International Nuclear Information System (INIS)

    Birdsall, B.; Andrews, J.; Ostler, G.; Tendler, S.J.B.; Feeney, J.; Roberts, G.C.K.; Davies, R.W.; Cheung, H.T.A.

    1989-01-01

    Two mutants of Lactobacillus casei dihydrofolate reductase, Trp 21 → Leu and Asp 26 → Glu, have been prepared by using site-directed mutagenesis methods, and their ligand binding and structural properties have been compared with those of the wild-type enzyme. 1 H, 13 C, and 31 P NMR studies have been carried out to characterize the structural changes in the complexes of the mutant and wild-type enzymes. Replacement of the conserved Trp 21 by a Leu residue causes a decrease in activity of the enzyme and reduces the NADPH binding constant by a factor of 400. The binding of substrates and substrate analogues is only slightly affected. 1 H NMR studies of the Trp 21 → Leu enzyme complexes have confirmed the original resonance assignments for Trp 21. In complexes formed with methotrexate and the mutant enzyme, the results indicate some small changes in conformation occurring as much as 14 angstrom away from the site of substitution. For the enzyme-NADPH complexes, the chemical shifts of nuclei in the bound coenzyme indicate that the nicotinamide ring binds differently in complexes with the mutant and the wild-type enzyme. There are complexes where the wild-type enzyme has been shown to exist in solution as a mixture of conformations, and studies on the corresponding complexes with the Trp 21 → Leu mutant indicate that the delicately poised equilibria can be perturbed. Some conformational adjustments are required to allow the carboxylate of Glu 26 to bind effectively to the N1 proton of inhibitors such as methotrexate and trimethoprim

  19. Use of the neutron diffraction - H/D exchange technique to determine the conformational dynamics of trypsin

    International Nuclear Information System (INIS)

    Kossiakoff, A.A.

    1982-01-01

    Reported here are studies analyzing the extent and nature of the inherent conformational fluctuations in trypsin by neutron diffraction - hydrogen exchange techniques. The pattern of exchange investigates systematic relationships between exchangeable sites and the structural and chemical properties of the molecule. Our findings that pH 7, 20 0 and 1 year of soaking all sites of trypsin are fully exchanged except those which are especially well protected by the structure. Essentially all the sites in which the peptide hydrogens are bonded directly to water molecules - either in the bulk solvent regions or in interior clusters - are fully exchanged. 41 references, 10 figures

  20. Discrepancies between conformational distributions of a polyalanine peptide in solution obtained from molecular dynamics force fields and amide I' band profiles.

    Science.gov (United States)

    Verbaro, Daniel; Ghosh, Indrajit; Nau, Werner M; Schweitzer-Stenner, Reinhard

    2010-12-30

    Structural preferences in the unfolded state of peptides determined by molecular dynamics still contradict experimental data. A remedy in this regard has been suggested by MD simulations with an optimized Amber force field ff03* ( Best, R. Hummer, G. J. Phys. Chem. B 2009 , 113 , 9004 - 9015 ). The simulations yielded a statistical coil distribution for alanine which is at variance with recent experimental results. To check the validity of this distribution, we investigated the peptide H-A(5)W-OH, which with the exception of the additional terminal tryptophan is analogous to the peptide used to optimize the force fields ff03*. Electronic circular dichroism, vibrational circular dichroism, and infrared spectroscopy as well as J-coupling constants obtained from NMR experiments were used to derive the peptide's conformational ensemble. Additionally, Förster resonance energy transfer between the terminal chromophores of the fluorescently labeled peptide analogue H-Dbo-A(5)W-OH was used to determine its average length, from which the end-to-end distance of the unlabeled peptide was estimated. Qualitatively, the experimental (3)J(H(N),C(α)), VCD, and ECD indicated a preference of alanine for polyproline II-like conformations. The experimental (3)J(H(N),C(α)) for A(5)W closely resembles the constants obtained for A(5). In order to quantitatively relate the conformational distribution of A(5) obtained with the optimized AMBER ff03* force field to experimental data, the former was used to derive a distribution function which expressed the conformational ensemble as a mixture of polyproline II, β-strand, helical, and turn conformations. This model was found to satisfactorily reproduce all experimental J-coupling constants. We employed the model to calculate the amide I' profiles of the IR and vibrational circular dichroism spectrum of A(5)W, as well as the distance between the two terminal peptide carbonyls. This led to an underestimated negative VCD couplet and an

  1. Volumetric modulated arc therapy for delivery of hypofractionated stereotactic lung radiotherapy: A dosimetric and treatment efficiency analysis

    International Nuclear Information System (INIS)

    McGrath, Samuel D.; Matuszak, Martha M.; Yan Di; Kestin, Larry L.; Martinez, Alvaro A.; Grills, Inga S.

    2010-01-01

    Purpose/objective(s): Volumetric modulated arc therapy (VMAT) allows for intensity-modulated radiation delivery during gantry rotation with dynamic MLC motion, variable dose rates and gantry speed modulation. We compared VMAT plans with 3D-CRT for hypofractionated lung radiotherapy. Materials/methods: Twenty-one 3D-CRT plans for Stage IA lung cancer previously treated stereotactically were selected. VMAT plans were generated by optimizing machine aperture shape and radiation intensity at 10 deg. intervals. A partial arc range of 180 deg. was manually selected to coincide with tumor location. The arc was resampled down to 5 deg. intervals to ensure dose calculation accuracy. Identical planning objectives were used for VMAT/3D-CRT. Parameters assessed included dose to PTV and organs-at-risk (OAR), monitor units, and multiple conformity and homogeneity indices. Plans were delivered to a phantom for time comparison. Results: Lung V 20/12.5/10/5 were less with VMAT (relative reduction 4.5%, p = .02; 3.2%, p = .01; 2.6%, p = .01; 4.2%, p = .03, respectively). Mean/maximum-doses to PTV, dose to additional OARs, 95% isodose line conformity, and target volume homogeneity were equivalent. VMAT improved conformity at both the 80% (1.87 vs. 1.93, p = .08) and 50% isodose lines (5.19 vs. 5.65, p = .01). Treatment times were reduced significantly with VMAT (mean 6.1 vs. 11.9 min, p < .01). Conclusions: Single arc VMAT planning achieves highly conformal dose distributions while controlling dose to critical structures, including significant reduction in lung dose volume parameters. Employing a VMAT technique decreases treatment times by 37-63%, reducing the chance of error introduced by intrafraction variation. The quality and efficiency of VMAT is ideally suited for stereotactic lung radiotherapy delivery.

  2. 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, P.

    2012-01-01

    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......-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...

  3. [The conformational dynamics of the tetramer hemoglobin molecule as revealed by hydrogen exchange. III. Influence of the heme removal].

    Science.gov (United States)

    Abaturov, L V; Nosova, N G; Shliapnikova, S V

    2006-01-01

    Two main types of conformational fluctuations--local and global are characteristic of the native protein structure and revealed by hydrogen exchange. The probability of those fluctuations changes to a different extent upon hemoglobin oxygenation, changing of pH, splitting of the intersubunit contacts. To compare with the influence of the heme removal the rate of the H-D exchange of the peptide NH atoms of the human apoHb was studied at the pH range 5.5-9.0 and temperature 10-38 degrees C by the IR spectroscopy. The removal of the heme increases the rate of the H-D exchange of the 80% peptide NH atoms with the factor retardation of the exchange rate (P) in the range approximately 10(2)-10(8). For the most of the peptide NH atoms the probability of the local fluctuations weakly depends on the temperature, the enthalpy changes upon all such local conformational transitions deltaH(op) degrees are 0-15 kcal/M. Characterized by the stronger temperature dependence the global fluctuations are not arised upon the temperature increases up to 38 degrees C at pH 7.0 inspite of in these conditions the slow denaturation and aggregation of apoHb begin to occur. Upon the destabilization of the apoHb structure by the simultaneous decreasing of pH to 5.5 and temperature to 10 degrees C the global fluctuations of the apoHb native structure described by deltaH(op)o < 0 begin to intensify. The mechanism of the overall intensification of the local fluctuations upon the heme removal, the peculiarity of the heat denaturation of apoHb in conditions, close to that existing upon the selfassembly of Hb in vivo, and analogy between low temperature global fluctuations and cold denaturation of globular proteins are discussed.

  4. Steered molecular dynamics simulations of a bacterial type IV pilus reveal characteristics of an experimentally-observed, force-induced conformational transition

    Science.gov (United States)

    Baker, Joseph; Biais, Nicolas; Tama, Florence

    2011-10-01

    Type IV pili (T4P) are long, filamentous structures that emanate from the cellular surface of many infectious bacteria. They are built from a 158 amino acid long subunit called pilin. T4P can grow to many micrometers in length, and can withstand large tension forces. During the infection process, pili attach themselves to host cells, and therefore naturally find themselves under tension. We investigated the response of a T4 pilus to a pulling force using the method of steered molecular dynamics (SMD) simulation. Our simulations expose to the external environment an amino acid sequence initially hidden in the native filament, in agreement with experimental data. Therefore, our simulations might be probing the initial stage of the transition to a force-induced conformation of the T4 pilus. Additional exposed amino acid sequences that might be useful targets for drugs designed to mitigate bacterial infection were also predicted.

  5. Conformality lost

    International Nuclear Information System (INIS)

    Kaplan, David B.; Lee, Jong-Wan; Son, Dam T.; Stephanov, Mikhail A.

    2009-01-01

    We consider zero-temperature transitions from conformal to nonconformal phases in quantum theories. We argue that there are three generic mechanisms for the loss of conformality in any number of dimensions: (i) fixed point goes to zero coupling, (ii) fixed point runs off to infinite coupling, or (iii) an IR fixed point annihilates with a UV fixed point and they both disappear into the complex plane. We give both relativistic and nonrelativistic examples of the last case in various dimensions and show that the critical behavior of the mass gap behaves similarly to the correlation length in the finite temperature Berezinskii-Kosterlitz-Thouless (BKT) phase transition in two dimensions, ξ∼exp(c/|T-T c | 1/2 ). We speculate that the chiral phase transition in QCD at large number of fermion flavors belongs to this universality class, and attempt to identify the UV fixed point that annihilates with the Banks-Zaks fixed point at the lower end of the conformal window.

  6. Combining EPR spectroscopy and X-ray crystallography to elucidate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals.

    Science.gov (United States)

    Consentius, Philipp; Gohlke, Ulrich; Loll, Bernhard; Alings, Claudia; Heinemann, Udo; Wahl, Markus C; Risse, Thomas

    2017-08-09

    Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling is used to investigate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals. Within a single crystal, the oriented ensemble of spin bearing moieties results in a strong angle dependence of the EPR spectra. A quantitative description of the EPR spectra requires the determination of the unit cell orientation with respect to the sample tube and the orientation of the spin bearing moieties within the crystal lattice. Angle dependent EPR spectra were analyzed by line shape simulations using the stochastic Liouville equation approach developed by Freed and co-workers and an effective Hamiltonian approach. The gain in spectral information obtained from the EPR spectra of single crystalline samples taken at different frequencies, namely the X-band and Q-band, allows us to discriminate between motional models describing the spectra of isotropic solutions similarly well. In addition, it is shown that the angle dependent single crystal spectra allow us to identify two spin label rotamers with very similar side chain dynamics. These results demonstrate the utility of single crystal EPR spectroscopy in combination with spectral line shape simulation techniques to extract valuable dynamic information not readily available from the analysis of isotropic systems. In addition, it will be shown that the loss of electron density in high resolution diffraction experiments at room temperature does not allow us to conclude that there is significant structural disorder in the system.

  7. In-vitro investigation of out-of-field cell survival following the delivery of conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans

    International Nuclear Information System (INIS)

    McGarry, Conor K; Hounsell, Alan R; Butterworth, Karl T; Trainor, Colman; McMahon, Stephen J; O'Sullivan, Joe M; Prise, Kevin M

    2012-01-01

    The aim of this work is to determine the out-of-field survival of cells irradiated with either the primary field or scattered radiation in the presence and absence of intercellular communication following delivery of conformal, IMRT and VMAT treatment plans. Single beam, conformal, IMRT and VMAT plans were created to deliver 3 Gy to half the area of a T80 flask containing either DU-145 or AGO-1522 cells allowing intercellular communication between the in- and out-of-field cell populations. The same plans were delivered to a similar custom made phantom used to hold two T25 culture flasks, one flask in-field and one out-of-field to allow comparison of cell survival responses when intercellular communication is physically inhibited. Plans were created for the delivery of 8 Gy to the more radio-resistant DU-145 cells only in the presence and absence of intercellular communication. Cell survival was determined by clonogenic assay. In both cell lines, the out-of-field survival was not statistically different between delivery techniques for either cell line or dose. There was however, a statistically significant difference between survival out-of-field when intercellular communication was intact (single T80 culture flask) or inhibited (multiple T25 culture flasks) to in-field for all plans. No statistically significant difference was observed in-field with or without cellular communication to out-of-field for all plans. These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields when cellular communication between differentially irradiated cell populations is present. This data is further evidence that refinement of existing radiobiological models to include indirect cell killing effects is required. (paper)

  8. Large optical conductivity of Dirac semimetal Fermi arc surface states

    Science.gov (United States)

    Shi, Li-kun; Song, Justin C. W.

    2017-08-01

    Fermi arc surface states, a hallmark of topological Dirac semimetals, can host carriers that exhibit unusual dynamics distinct from that of their parent bulk. Here we find that Fermi arc carriers in intrinsic Dirac semimetals possess a strong and anisotropic light-matter interaction. This is characterized by a large Fermi arc optical conductivity when light is polarized transverse to the Fermi arc; when light is polarized along the Fermi arc, Fermi arc optical conductivity is significantly muted. The large surface spectral weight is locked to the wide separation between Dirac nodes and persists as a large Drude weight of Fermi arc carriers when the system is doped. As a result, large and anisotropic Fermi arc conductivity provides a novel means of optically interrogating the topological surfaces states of Dirac semimetals.

  9. 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

  10. 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.

  11. 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

    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......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...... and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations....

  12. 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.

  13. Comparison study of intensity modulated arc therapy using single or multiple arcs to intensity modulated radiation therapy for high-risk prostate cancer

    International Nuclear Information System (INIS)

    Ashamalla, Hani; Tejwani, Ajay; Parameritis, Loannis; Swamy, Uma; Luo, Pei Ching; Guirguis, Adel; Lavaf, Amir

    2013-01-01

    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 P ), right pelvic (PTV RtLN ) and left pelvic lymph nodes (PTV LtLN ), and organs at risk were contoured. PTVP, PTV RtLN , and PTV LtLN received 50.40 Gy followed by a boost to PTV 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 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 MEAN of bladder was within 2% of each other. The rectum D 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.

  14. High Affinity vs. Native Fibronectin in the Modulation of αvβ3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design.

    Directory of Open Access Journals (Sweden)

    Antonella Paladino

    2017-01-01

    Full Text Available Understanding how binding events modulate functional motions of multidomain proteins is a major issue in chemical biology. We address several aspects of this problem by analyzing the differential dynamics of αvβ3 integrin bound to wild type (wtFN10, agonist or high affinity (hFN10, antagonist mutants of fibronectin. We compare the dynamics of complexes from large-scale domain motions to inter-residue coordinated fluctuations to characterize the distinctive traits of conformational evolution and shed light on the determinants of differential αvβ3 activation induced by different FN sequences. We propose an allosteric model for ligand-based integrin modulation: the conserved integrin binding pocket anchors the ligand, while different residues on the two FN10's act as the drivers that reorganize relevant interaction networks, guiding the shift towards inactive (hFN10-bound or active states (wtFN10-bound. We discuss the implications of results for the design of integrin inhibitors.

  15. Conformational fluctuation dynamics of domain I of human serum albumin in the course of chemically and thermally induced unfolding using fluorescence correlation spectroscopy.

    Science.gov (United States)

    Yadav, Rajeev; Sengupta, Bhaswati; Sen, Pratik

    2014-05-22

    The present study elucidates the involvement of conformational fluctuation dynamics during chemically and thermally induced unfolding of human serum albumin (HSA) by fluorescence correlation spectroscopic (FCS) study, time-resolved fluorescence measurements, and circular dichroism (CD) spectroscopic methods. Two fluorescent probes, tetramethylrhodamine-5-maleimide (TMR) and N-(7-dimethylamino-4-methylcoumarin-3-yl) iodoacetamide (DACIA) were used to selectively label the domain I of HSA through the reaction with cys-34 for these studies. The guanidine hydrochloride (GnHCl) induced global structural change of HSA is monitored through its hydrodynamic radius (r(H)) and CD response, which is found to be two step in nature. In FCS experiment, along with the diffusion time component we have observed an exponential relaxation time component (τ(R)) that has been ascribed to the concerted chain dynamics of HSA. Unlike in the global structural change, we found that the τ(R) value changes in a different manner in the course of the unfolding. The dependence of τ(R) on the concentration of GnHCl was best fitted with a four state model, indicating the involvement of two intermediate states during the unfolding process, which were not observed through the CD response and r(H) data. The fluorescence lifetime measurement also supports our observation of intermediate states during the unfolding of HSA. However, no such intermediate states were observed during thermally induced unfolding of HSA.

  16. 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.

  17. Plan quality comparison between 4-arc and 6-arc noncoplanar volumetric modulated arc stereotactic radiotherapy for the treatment of multiple brain metastases.

    Science.gov (United States)

    Yoshio, Kotaro; Mitsuhashi, Toshiharu; Wakita, Akihisa; Kitayama, Takahiro; Hisazumi, Kento; Inoue, Daisaku; Shiode, Tsuyoki; Akaki, Shiro; Kanazawa, Susumu

    2018-01-04

    To compare the plans of 4-arc and 6-arc noncoplanar volumetric modulated arc stereotactic radiotherapy (VMA-SRT) for multiple brain metastases and to investigate the cutoff value for the tumor number and volume for 6-arc rather than 4-arc VMA-SRT. We identified 24 consecutive multiple-target cases (3 to 19 targets in each case) with 189 total targets. We constructed plans using both 4- and 6-arc noncoplanar VMA-SRT. The prescribed dose was 36 Gy/6 fr, and it was delivered to 95% of the planning target volume (PTV). The plans were evaluated for the dose conformity using the Radiation Therapy Oncology Group and Paddick conformity indices (RCI and PCI), fall-off (Paddick gradient index [PGI]), and the normal brain dose. The median (range) RCI, PCI, and PGI was 0.94 (0.92 to 0.99), 0.89 (0.77 to 0.94), and 3.75 (2.24 to 6.54) for the 4-arc plan and 0.94 (0.91 to 0.98), 0.89 (0.76 to 0.94), and 3.65 (2.24 to 6.5) for the 6-arc plan, respectively. The median (range) of the normal brain dose was 910.3 cGy (381.4 to 1268.9) for the 4-arc plan and 898.8 cGy (377 to 1252.9) for the 6-arc plan. The PGI of the 6-arc plan was significantly superior to that of the 4-arc plan (p = 0.0076), and the optimal cutoff values for the tumor number and volume indicative of 6-arc (and not 4-arc) VMA-SRT were cases with ≥ 5 metastases and a PTV of ≥ 12.9 mL, respectively. The PCI values, however, showed no significant difference between the 2 plans. We believe these results will help in considering the use of 6-arc VMA-SRT for multiple brain metastases. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  18. Influence of a charged graphene surface on the orientation and conformation of covalently attached oligonucleotides: a molecular dynamics study

    Czech Academy of Sciences Publication Activity Database

    Kabeláč, Martin; Kroutil, O.; Předota, M.; Lankaš, Filip; Šíp, M.

    2012-01-01

    Roč. 14, č. 12 (2012), s. 4217-4229 ISSN 1463-9076 R&D Projects: GA ČR GC204/09/J010; GA MŠk LC512; GA AV ČR IAA400550808 Grant - others:GA ČR(CZ) GA203/08/0094; GA MŠk(CZ) LM2010005 Program:GA Institutional research plan: CEZ:AV0Z40550506 Keywords : DNA * graphene * charge density * molecular dynamics * Amber Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.829, year: 2012

  19. Ligand induced change of β2 adrenergic receptor from active to inactive conformation and its implication for the closed/open state of the water channel: insight from molecular dynamics simulation, free energy calculation and Markov state model analysis.

    Science.gov (United States)

    Bai, Qifeng; Pérez-Sánchez, Horacio; Zhang, Yang; Shao, Yonghua; Shi, Danfeng; Liu, Huanxiang; Yao, Xiaojun

    2014-08-14

    The reported crystal structures of β2 adrenergic receptor (β2AR) reveal that the open and closed states of the water channel are correlated with the inactive and active conformations of β2AR. However, more details about the process by which the water channel states are affected by the active to inactive conformational change of β2AR remain illusive. In this work, molecular dynamics simulations are performed to study the dynamical inactive and active conformational change of β2AR induced by inverse agonist ICI 118,551. Markov state model analysis and free energy calculation are employed to explore the open and close states of the water channel. The simulation results show that inverse agonist ICI 118,551 can induce water channel opening during the conformational transition of β2AR. Markov state model (MSM) analysis proves that the energy contour can be divided into seven states. States S1, S2 and S5, which represent the active conformation of β2AR, show that the water channel is in the closed state, while states S4 and S6, which correspond to the intermediate state conformation of β2AR, indicate the water channel opens gradually. State S7, which represents the inactive structure of β2AR, corresponds to the full open state of the water channel. The opening mechanism of the water channel is involved in the ligand-induced conformational change of β2AR. These results can provide useful information for understanding the opening mechanism of the water channel and will be useful for the rational design of potent inverse agonists of β2AR.

  20. 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.

  1. Bovine pancreatic polypeptide (bPP) undergoes significant changes in conformation and dynamics upon binding to DPC micelles.

    Science.gov (United States)

    Lerch, Mirjam; Gafner, Verena; Bader, Reto; Christen, Barbara; Folkers, Gerd; Zerbe, Oliver

    2002-10-04

    The pancreatic polypeptide (PP), a 36-residue, C-terminally amidated polypeptide hormone is a member of the neuropeptide Y (NPY) family. Here, we have studied the structure and dynamics of bovine pancreatic polypeptide (bPP) when bound to DPC-micelles as a membrane-mimicking model as well as the dynamics of bPP in solution. The comparison of structure and dynamics of bPP in both states reveals remarkable differences. The overall correlation time of 5.08ns derived from the 15N relaxation data proves unambiguously that bPP in solution exists as a dimer. Therein, intermolecular as well as intramolecular hydrophobic interactions from residues of both the amphiphilic helix and of the back-folded N terminus contribute to the stability of the PP fold. The overall rigidity is well-reflected in positive values for the heteronuclear NOE for residues 4-34. The membrane-bound species displays a partitioning into a more flexible N-terminal region and a well-defined alpha-helical region comprising residues 17-31. The average RMSD value for residues 17-31 is 0.22(+/-0.09)A. The flexibility of the N terminus is compatible with negative values of the heteronuclear NOE observed for the N-terminal residues 4-12 and low values of the generalized order parameter S(2). The membrane-peptide interface was investigated by micelle-integrating spin-labels and H,2H exchange measurements. It is formed by those residues which make contacts between the C-terminal alpha-helix and the polyproline helix. In contrast to pNPY, also residues from the N terminus display spatial proximity to the membrane interface. Furthermore, the orientation of the C terminus, that presumably contains residues involved in receptor binding, is different in the two environments. We speculate that this pre-positioning of residues could be an important requirement for receptor activation. Moreover, we doubt that the PP fold is of functional relevance for binding at the Y(4) receptor.

  2. 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)

  3. Exploring virtualisation tools with a new virtualisation provisioning method to test dynamic grid environments for ALICE grid jobs over ARC grid middleware

    International Nuclear Information System (INIS)

    Wagner, B; Kileng, B

    2014-01-01

    The Nordic Tier-1 centre for LHC is distributed over several computing centres. It uses ARC as the internal computing grid middleware. ALICE uses its own grid middleware AliEn to distribute jobs and the necessary software application stack. To make use of most of the AliEn infrastructure and software deployment methods for running ALICE grid jobs on ARC, we are investigating different possible virtualisation technologies. For this a testbed and possible framework for bridging different middleware systems is under development. It allows us to test a variety of virtualisation methods and software deployment technologies in the form of different virtual machines.

  4. Commissioning and first clinical application of mARC treatment

    International Nuclear Information System (INIS)

    Dzierma, Yvonne; Nuesken, Frank G.; Kremp, Stephanie; Palm, Jan; Licht, Norbert P.; Ruebe, Christian

    2014-01-01

    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.) [de

  5. Quality assurance of geometric accuracy based on an electronic portal imaging device and log data analysis for Dynamic WaveArc irradiation.

    Science.gov (United States)

    Hirashima, Hideaki; Miyabe, Yuki; Nakamura, Mitsuhiro; Mukumoto, Nobutaka; Mizowaki, Takashi; Hiraoka, Masahiro

    2018-04-06

    The purpose of this study was to develop a simple verification method for the routine quality assurance (QA) of Dynamic WaveArc (DWA) irradiation using electronic portal imaging device (EPID) images and log data analysis. First, an automatic calibration method utilizing the outermost multileaf collimator (MLC) slits was developed to correct the misalignment between the center of the EPID and the beam axis. Moreover, to verify the detection accuracy of the MLC position according to the EPID images, various positions of the MLC with intentional errors in the range 0.1-1 mm were assessed. Second, to validate the geometric accuracy during DWA irradiation, tests were designed in consideration of three indices. Test 1 evaluated the accuracy of the MLC position. Test 2 assessed dose output consistency with variable dose rate (160-400 MU/min), gantry speed (2.2-6°/s), and ring speed (0.5-2.7°/s). Test 3 validated dose output consistency with variable values of the above parameters plus MLC speed (1.6-4.2 cm/s). All tests were delivered to the EPID and compared with those obtained using a stationary radiation beam with a 0° gantry angle. Irradiation log data were recorded simultaneously. The 0.1-mm intentional error on the MLC position could be detected by the EPID, which is smaller than the EPID pixel size. In Test 1, the MLC slit widths agreed within 0.20 mm of their exposed values. The averaged root-mean-square error (RMSE) of the dose outputs was less than 0.8% in Test 2 and Test 3. Using log data analysis in Test 3, the RMSE between the planned and recorded data was 0.1 mm, 0.12°, and 0.07° for the MLC position, gantry angle, and ring angle, respectively. The proposed method is useful for routine QA of the accuracy of DWA. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  6. Monitoring ARC services with GangliARC

    International Nuclear Information System (INIS)

    Cameron, D; Karpenko, D

    2012-01-01

    Monitoring of Grid services is essential to provide a smooth experience for users and provide fast and easy to understand diagnostics for administrators running the services. GangliARC makes use of the widely-used Ganglia monitoring tool to present web-based graphical metrics of the ARC computing element. These include statistics of running and finished jobs, data transfer metrics, as well as showing the availability of the computing element and hardware information such as free disk space left in the ARC cache. Ganglia presents metrics as graphs of the value of the metric over time and shows an easily-digestable summary of how the system is performing, and enables quick and easy diagnosis of common problems. This paper describes how GangliARC works and shows numerous examples of how the generated data can quickly be used by an administrator to investigate problems. It also presents possibilities of combining GangliARC with other commonly-used monitoring tools such as Nagios to easily integrate ARC monitoring into the regular monitoring infrastructure of any site or computing centre.

  7. Discharge Characteristics of DC Arc Water Plasma for Environmental Applications

    Science.gov (United States)

    Li, Tianming; Sooseok, Choi; Takayuki, Watanabe

    2012-12-01

    A water plasma was generated by DC arc discharge with a hafnium embedded rod-type 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. Discharge Characteristics of DC Arc Water Plasma for Environmental Applications

    International Nuclear Information System (INIS)

    Choi, Sooseok; Watanabe, Takayuki; Li Tianming

    2012-01-01

    A water plasma was generated by DC arc discharge with a hafnium embedded rod-type 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. (plasma technology)

  9. Solution conformation and dynamics of a tetrasaccharide related to the LewisX antigen deduced by NMR relaxation measurements

    International Nuclear Information System (INIS)

    Poveda, Ana; Asensio, Juan Luis; Martin-Pastor, Manuel; Jimenez-Barbero, Jesus

    1997-01-01

    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-α-N-acetyl-galactosaminyl-β-galactopyranosyl-(1 → 4)[3-O-α-fucosyl] -glucopyranoside (1), an inhibitor of astrocyte growth. In addition, 13 C-NMR relaxation data have also been recorded at both fields. The 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 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 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 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

  10. 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.

  11. Volumetric modulated arc radiotherapy for esophageal cancer

    International Nuclear Information System (INIS)

    Vivekanandan, Nagarajan; Sriram, Padmanaban; Syam Kumar, S.A.; Bhuvaneswari, Narayanan; Saranya, Kamalakannan

    2012-01-01

    A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc (RA) against 3D conformal radiation therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT) techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA plans were generated with the aim to spare organs at risk (OAR) and healthy tissue while enforcing highly conformal target coverage. The planning objective was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans were evaluated based on target conformity and dose-volume histograms of organs at risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery time were also evaluated to measure the treatment efficiency. The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT. Target conformity improved with RA plans compared with IMRT. The mean lung dose was similar in all techniques. However, RA plans showed a reduction in the volume of the lung irradiated at V 20Gy and V 30Gy dose levels (range, 4.62–17.98%) compared with IMRT plans. The mean dose and D 35% of heart for the RA plans were better than the IMRT by 0.5–5.8%. Mean V 10Gy and integral dose to healthy tissue were almost similar in all techniques. But RA plans resulted in a reduced low-level dose bath (15–20 Gy) in the range of 14–16% compared with IMRT plans. The average MU needed to deliver the prescribed dose by RA technique was reduced by 20–25% compared with IMRT technique. The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time, whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans.

  12. Some considerations concerning volume-modulated arc therapy: a stepping stone towards a general theory

    International Nuclear Information System (INIS)

    Webb, S; McQuaid, D

    2009-01-01

    In this paper it is formally shown that the dynamic multileaf collimator (MLC) IMRT delivery technique remains valid if the MLC is supported on a 1D moving platform. It is also shown that, in such circumstances, it is always time preferable to deliver overlapping modulating fields as a single swept field rather than as separate fields. The most general formulism is presented and then related to simpler equations in limiting cases. The paper explains in detail how a 'small-arc approximation' can be invoked to relate the 1D linear theory to the MLC-on-moving-platform-(gantry) delivery technique involving rotation therapy and known as volume-modulated arc therapy (VMAT). It is explained how volume-modulated arc therapy delivered with open unmodulated fields and which can deliver conformal dose distributions can be interpreted as an IMRT delivery. The (Elekta adopted) term VMAT will be used in a generic sense to include a similar (Varian) method known as RapidArc. Approximate expressions are derived for the 'amount of modulation' possible in a VMAT delivery. This paper does not discuss the actual VMAT planning but gives an insight at a deep level into VMAT delivery. No universal theory of VMAT is known in the sense that there is no theory that can predict precisely the performance of a VMAT delivery in terms of the free parameters available (variable gantry speed, variable fluence-delivery rate, set of MLC shapes, MLC orientation, number of arcs, coplanarity versus non-coplanarity, etc). This is in stark contrast to the situation with several other IMRT delivery techniques where such theoretical analyses are known. In this paper we do not provide such a theory; the material presented is a stepping stone on the path towards this.

  13. Role of DNA conformation & energetic insights in Msx-1-DNA recognition as revealed by molecular dynamics studies on specific and nonspecific complexes.

    Science.gov (United States)

    Kachhap, Sangita; Singh, Balvinder

    2015-01-01

    In most of homeodomain-DNA complexes, glutamine or lysine is present at 50th position and interacts with 5th and 6th nucleotide of core recognition region. Molecular dynamics simulations of Msx-1-DNA complex (Q50-TG) and its variant complexes, that is specific (Q50K-CC), nonspecific (Q50-CC) having mutation in DNA and (Q50K-TG) in protein, have been carried out. Analysis of protein-DNA interactions and structure of DNA in specific and nonspecific complexes show that amino acid residues use sequence-dependent shape of DNA to interact. The binding free energies of all four complexes were analysed to define role of amino acid residue at 50th position in terms of binding strength considering the variation in DNA on stability of protein-DNA complexes. The order of stability of protein-DNA complexes shows that specific complexes are more stable than nonspecific ones. Decomposition analysis shows that N-terminal amino acid residues have been found to contribute maximally in binding free energy of protein-DNA complexes. Among specific protein-DNA complexes, K50 contributes more as compared to Q50 towards binding free energy in respective complexes. The sequence dependence of local conformation of DNA enables Q50/Q50K to make hydrogen bond with nucleotide(s) of DNA. The changes in amino acid sequence of protein are accommodated and stabilized around TAAT core region of DNA having variation in nucleotides.

  14. 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.

    2017-09-01

    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.

  15. Conformal Tachyons

    CERN Document Server

    Tomaschitz, R

    2000-01-01

    We study tachyons conformally coupled to the background geometry of a Milne universe. The causality of superluminal signal transfer is scrutinized in this context. The cosmic time of the comoving frame determines a distinguished time order for events connected by superluminal signals. An observer can relate his rest frame to the galaxy frame, and compare so the time order of events in his proper time to the cosmic time order. All observers can in this way arrive at identical conclusions on the causality of events connected by superluminal signals. An unambiguous energy concept for tachyonic rays is defined by means of the cosmic time of the comoving reference frame, without resorting to an antiparticle interpretation. On that basis we give an explicit proof that no signals can be sent into the past of observers. Causality violating signals are energetically forbidden, as they would have negative energy in the rest frame of the emitting observer. If an observer emits a superluminal signal, the tachyonic respon...

  16. Electric arc hydrogen heaters

    International Nuclear Information System (INIS)

    Zasypin, I.M.

    2000-01-01

    The experimental data on the electric arc burning in hydrogen are presented. Empirical and semiempirical dependences for calculating the arc characteristics are derived. An engineering method of calculating plasma torches for hydrogen heating is proposed. A model of interaction of a hydrogen arc with a gas flow is outlined. The characteristics of plasma torches for heating hydrogen and hydrogen-bearing gases are described. (author)

  17. Dosimetric comparison of helical tomotherapy, RapidArc, and a novel IMRT and Arc technique for esophageal carcinoma

    International Nuclear Information System (INIS)

    Martin, Spencer; Chen, Jeff Z.; Rashid Dar, A.; Yartsev, Slav

    2011-01-01

    Purpose: To compare radiotherapy treatment plans for mid- and distal-esophageal cancer with primary involvement of the gastroesophageal (GE) junction using a novel IMRT and Arc technique (IMRT and Arc), helical tomotherapy (HT), and RapidArc (RA1 and RA2). Methods and materials: Eight patients treated on HT for locally advanced esophageal cancer with radical intent were re-planned for RA and IMRT and Arc. RA plans employed single and double arcs (RA1 and RA2, respectively), while IMRT and Arc plans had four fixed-gantry IMRT fields and a conformal arc. Dose-volume histogram statistics, dose uniformity, and dose homogeneity were analyzed to compare treatment plans. Results: RA2 plans showed significant improvement over RA1 plans in terms of OAR dose and PTV dose uniformity and homogeneity. HT plan provided best dose uniformity (p = 0.001) and dose homogeneity (p = 0.002) to planning target volume (PTV), while IMRT and Arc and RA2 plans gave lowest dose to lungs among four radiotherapy techniques with acceptable PTV dose coverage. Mean V 10 of the lungs was significantly reduced by the RA2 plans compared to IMRT and Arc (40.3%, p = 0.001) and HT (66.2%, p 15 of the lungs for the RA2 plans also showed significant improvement over the IMRT and Arc (25.2%, p = 0.042) and HT (34.8%, p = 0.027) techniques. These improvements came at the cost of higher doses to the heart volume compared to HT and IMRT and Arc techniques. Mean lung dose (MLD) for the IMRT and Arc technique (21.2 ± 5.0% of prescription dose) was significantly reduced compared to HT (26.3%, p = 0.004), RA1 (23.3%, p = 0.028), and RA2 (23.2%, p = 0.017) techniques. Conclusion: The IMRT and Arc technique is a good option for treating esophageal cancer with thoracic involvement. It achieved optimal low dose to the lungs and heart with acceptable PTV coverage. HT is a good option for treating esophageal cancer with little thoracic involvement as it achieves superior dose conformality and uniformity. The RA2

  18. 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.

  19. Multiphysics Simulation of Welding-Arc and Nozzle-Arc System: Mathematical-Model, Solution-Methodology and Validation

    Science.gov (United States)

    Pawar, Sumedh; Sharma, Atul

    2018-01-01

    This work presents mathematical model and solution methodology for a multiphysics engineering problem on arc formation during welding and inside a nozzle. A general-purpose commercial CFD solver ANSYS FLUENT 13.0.0 is used in this work. Arc formation involves strongly coupled gas dynamics and electro-dynamics, simulated by solution of coupled Navier-Stoke equations, Maxwell's equations and radiation heat-transfer equation. Validation of the present numerical methodology is demonstrated with an excellent agreement with the published results. The developed mathematical model and the user defined functions (UDFs) are independent of the geometry and are applicable to any system that involves arc-formation, in 2D axisymmetric coordinates system. The high-pressure flow of SF6 gas in the nozzle-arc system resembles arc chamber of SF6 gas circuit breaker; thus, this methodology can be extended to simulate arcing phenomenon during current interruption.

  20. 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.

  1. Conformal field theory in conformal space

    International Nuclear Information System (INIS)

    Preitschopf, C.R.; Vasiliev, M.A.

    1999-01-01

    We present a new framework for a Lagrangian description of conformal field theories in various dimensions based on a local version of d + 2-dimensional conformal space. The results include a true gauge theory of conformal gravity in d = (1, 3) and any standard matter coupled to it. An important feature is the automatic derivation of the conformal gravity constraints, which are necessary for the analysis of the matter systems

  2. Can advanced new radiation therapy technologies improve outcome of high grade glioma (HGG) patients? analysis of 3D-conformal radiotherapy (3DCRT) versus volumetric-modulated arc therapy (VMAT) in patients treated with surgery, concomitant and adjuvant chemo-radiotherapy

    International Nuclear Information System (INIS)

    Navarria, Pierina; Pessina, Federico; Cozzi, Luca; Ascolese, Anna Maria; Lobefalo, Francesca; Stravato, Antonella; D’Agostino, Giuseppe; Franzese, Ciro; Caroli, Manuela; Bello, Lorenzo; Scorsetti, Marta

    2016-01-01

    To assess the impact of volumetric-modulated arc therapy (VMAT) compared with 3D-conformal radiotherapy (3DCRT) in patients with newly diagnosed high grade glioma in terms of toxicity, progression free survival (PFS) and overall survival (OS). From March 2004 to October 2014, 341 patients underwent surgery followed by concomitant and adjuvant chemo-radiotherapy. From 2003 to 2010, 167 patients were treated using 3DCRT; starting from 2011, 174 patients underwent VMAT. The quantitative evaluation of the treatment plans was performed by means of standard dose volume histogram analysis. Response was recorded using the Response Assessment in Neuro-Oncology (RANO) criteria and toxicities graded according to Common Terminology Criteria for Adverse Event version 4.0. Both techniques achieved an adequate dose conformity to the target. The median follow up time was 1.3 years; at the last observation 76 patients (23.4 %) were alive and 249 (76.6 %) dead (16 patients were lot to follow-up). For patients who underwent 3DCRT, the median PFS was 0.99 ± 0.07 years (CI95: 0.9–1.1 years); the 1 and 3 years PFS were, 49.6 ± 4 and 19.1 ± 3.1 %. This shall be compared, respectively, to 1.29 ± 0.13 years (CI95: 1.01–1.5 years), 60.8 ± 3.8, and 29.7 ± 4.6 % for patients who underwent VMAT (p = 0.02). The median OS for 3DCRT patients was 1.21 ± 0.09 years (CI95:1.03–1.3 years); 1 and 5 year OS was, 63.3 ± 3.8 and 21.5 ± 3.3 %. The corresponding results for 3DRCT patients were 1.56 ± 0.09 years (CI95:1.37–1.74 years), 73.4 ± 3.5, 30 ± 4.6 % respectively (p < 0.01). In both groups, prognostic factors conditioning PFS and OS were age, gender, KPS, histology and extent of resection (EOR). VMAT resulted superior to 3DCRT in terms of dosimetric findings and clinical results

  3. Conformal dimension theory and application

    CERN Document Server

    Mackay, John M

    2010-01-01

    Conformal dimension measures the extent to which the Hausdorff dimension of a metric space can be lowered by quasisymmetric deformations. Introduced by Pansu in 1989, this concept has proved extremely fruitful in a diverse range of areas, including geometric function theory, conformal dynamics, and geometric group theory. This survey leads the reader from the definitions and basic theory through to active research applications in geometric function theory, Gromov hyperbolic geometry, and the dynamics of rational maps, amongst other areas. It reviews the theory of dimension in metric spaces and of deformations of metric spaces. It summarizes the basic tools for estimating conformal dimension and illustrates their application to concrete problems of independent interest. Numerous examples and proofs are provided. Working from basic definitions through to current research areas, this book can be used as a guide for graduate students interested in this field, or as a helpful survey for experts. Background needed ...

  4. SU-E-T-393: Evaluation of Large Field IMRT Versus RapidArc Planning for Carcinoma Cervix with Para-Aotic Node Irradiation

    International Nuclear Information System (INIS)

    Raman, S Kothanda; Girigesh, Y; MISHRA, M; Lalit, K

    2015-01-01

    Purpose: The objective of this work is to evaluate and compare Large field IMRT and RapidArc planning for Carcinoma Cervix and Para-aotic node irradiation. Methods: In this study, ten patients of Cervix with para-aotic node have been selected with PTV length 35+2cm. All plans were generated in Eclipse TPS V10.0 with Dynamic IMRT and RapidArc technique using 6MV photon energy. In IMRT planning, 7 fields were chosen to get optimal plan and in RapidArc, double Full arc clockwise and counter clockwise were used for planning. All the plans were generated with single isocenter and calculated using AAA dose algorithm. For all the cases the prescribed dose to PTV was same and the plan acceptance criteria is; 95% of the PTV volume should receive 100% prescribed dose. The tolerance doses for the OAR’s is also taken in to account. The evaluation criteria used for analysis are; 1) Homogeneity Index, 2) Conformity Index, 3) Mean Dose to OAR’s, 4)Total monitor units delivered. Results: DVH analysis were performed for both IMRT and RapidArc planning. In both the plans, 95% of PTV volume receives prescribed dose and maximum dose are less than 107%. The conformity index are same in both the techniques. The mean Homogeneity index are 1.036 and 1.053 for IMRT and RapidArc plan. The mean (mean + SD) dose of bladder and rectum in IMRT is 44.2+1.55, 42.05+2.52 and RapidArc is 46.66+1.6, 44.2+2.75 respectively. There is no significant difference found in Right Femoral head, Left Femoral head and Kidney doses. It is found that total MU’s are more in IMRT compared with RapidArc planning. Conclusion: In the case of cervix with Para-arotic node single isocenter irradiation, IMRT planning in large-field is better compared to RapidArc planning in terms of Homogeneity Index and mean dose of Bladder and Rectum

  5. SU-E-T-393: Evaluation of Large Field IMRT Versus RapidArc Planning for Carcinoma Cervix with Para-Aotic Node Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Raman, S Kothanda; Girigesh, Y; MISHRA, M; Lalit, K [Rajiv Gandhi Cancer Institute & Research Centre, New Delhi (India)

    2015-06-15

    Purpose: The objective of this work is to evaluate and compare Large field IMRT and RapidArc planning for Carcinoma Cervix and Para-aotic node irradiation. Methods: In this study, ten patients of Cervix with para-aotic node have been selected with PTV length 35+2cm. All plans were generated in Eclipse TPS V10.0 with Dynamic IMRT and RapidArc technique using 6MV photon energy. In IMRT planning, 7 fields were chosen to get optimal plan and in RapidArc, double Full arc clockwise and counter clockwise were used for planning. All the plans were generated with single isocenter and calculated using AAA dose algorithm. For all the cases the prescribed dose to PTV was same and the plan acceptance criteria is; 95% of the PTV volume should receive 100% prescribed dose. The tolerance doses for the OAR’s is also taken in to account. The evaluation criteria used for analysis are; 1) Homogeneity Index, 2) Conformity Index, 3) Mean Dose to OAR’s, 4)Total monitor units delivered. Results: DVH analysis were performed for both IMRT and RapidArc planning. In both the plans, 95% of PTV volume receives prescribed dose and maximum dose are less than 107%. The conformity index are same in both the techniques. The mean Homogeneity index are 1.036 and 1.053 for IMRT and RapidArc plan. The mean (mean + SD) dose of bladder and rectum in IMRT is 44.2+1.55, 42.05+2.52 and RapidArc is 46.66+1.6, 44.2+2.75 respectively. There is no significant difference found in Right Femoral head, Left Femoral head and Kidney doses. It is found that total MU’s are more in IMRT compared with RapidArc planning. Conclusion: In the case of cervix with Para-arotic node single isocenter irradiation, IMRT planning in large-field is better compared to RapidArc planning in terms of Homogeneity Index and mean dose of Bladder and Rectum.

  6. 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

    H-1 NMR (400 MHz) spectra of the indole alkaloid dihydrocorynantheine recorded at room temperature show the presence of two conformers near coalescence. Low temperature H-1 NMR allowed characterization of the conformational equilibrium, which involves rotation of the 3-methoxypropenoate side chain...... 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...

  7. The investigation of movement dynamics of an AC electric arc attachment along the working surface of a hollow cylindrical electrode under the action of gas-dynamic and electromagnetic forces

    International Nuclear Information System (INIS)

    Surov, A V; Popov, S D; Serba, E O; Nakonechny, G V; Spodobin, V A; Ovchinnikov, R V; Kumkova, I I; Shabalin, S A

    2012-01-01

    Stationary electric arc alternating current plasma torches are used today for realization of plasma chemical technologies requiring relatively high energy input. Waste treatment is one these directions. The paper reports on experiment results directed towards the increase in the lifetime characteristics of electrode units of the powerful high-voltage electric-arc AC plasma torches. The solution to the problem of obtainment the uniform wear of a copper hollow cylindrical electrode achieved by the controlled movement of the arc attachment along the working surface was offered. Organization of gas supply in the near electrode area and application of alternating magnetic field ensured movement of arc attachment along the surface with average speed from 2 to 14 m/s. Arc current was about 47 A and 84 A, gas flow rate in near electrode area was about 5 and 4.5 g/s. Due to researches on the experimental prototype of a hollow cylindrical electrode, the erosion of its material reached only 3 μg/C, that enables production of the electrode assembly with life time above 1000 hours at currents in the arc up to 100–200 A.

  8. Conformational Change in the Mechanism of Inclusion of Ketoprofen in β-Cyclodextrin: NMR Spectroscopy, Ab Initio Calculations, Molecular Dynamics Simulations, and Photoreactivity.

    Science.gov (United States)

    Guzzo, T; Mandaliti, W; Nepravishta, R; Aramini, A; Bodo, E; Daidone, I; Allegretti, M; Topai, A; Paci, M

    2016-10-11

    Inclusion of drugs in cyclodextrins (CDs) is a recognized tool for modifying several properties such as solubility, stability, bioavailability, and so on. The photoreactive behavior of the β-CD/ketoprofen (KP) complex upon UV exposure showed a significant increase in photodecarboxylation, whereas the secondary degradation products by hydroxylation of the benzophenone moiety were inhibited. The results may account for an improvement of KP photophysical properties upon inclusion, thus better fostering its topical use. To correlate the structural details of the inclusion with these results, an NMR spectroscopic study of KP upon inclusion in β-CD was performed. Effects of the magnetically anisotropic centers of KP, changing their orientations upon inclusion and giving chemical shift variations, were specifically correlated with the results of the molecular dynamic simulations and ab initio calculations. In the large variety of papers focusing on the structural analysis of β-CD complexes, this work represents one of the few examples in which a detailed analysis of these simultaneous upfield-downfield NMR shifts of the same aromatic molecule upon inclusion is reported. Interestingly, the results demonstrate that the observed upfield and downfield shifts upon inclusion are not related to any direct magnetic role of β-CD. The conformational change of KP upon the inclusion process consists of a slight reduction in the angle between the two phenyl rings and in a remarkable reduction in the mobility of the carboxyl group, the latter being one of the main contributions to the NMR resonance shifts. These structural details help in understanding the features of the inclusion complex and, eventually, the driving force for its formation.

  9. Conformational Ensembles of an Intrinsically Disordered Protein pKID with and without a KIX Domain in Explicit Solvent Investigated by All-Atom Multicanonical Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Haruki Nakamura

    2012-02-01

    Full Text Available The phosphorylated kinase-inducible activation domain (pKID adopts a helix–loop–helix structure upon binding to its partner KIX, although it is unstructured in the unbound state. The N-terminal and C-terminal regions of pKID, which adopt helices in the complex, are called, respectively, αA and αB. We performed all-atom multicanonical molecular dynamics simulations of pKID with and without KIX in explicit solvents to generate conformational ensembles. Although the unbound pKID was disordered overall, αA and αB exhibited a nascent helix propensity; the propensity of αA was stronger than that of αB, which agrees with experimental results. In the bound state, the free-energy landscape of αB involved two low free-energy fractions: native-like and non-native fractions. This result suggests that αB folds according to the induced-fit mechanism. The αB-helix direction was well aligned as in the NMR complex structure, although the αA helix exhibited high flexibility. These results also agree quantitatively with experimental observations. We have detected that the αB helix can bind to another site of KIX, to which another protein MLL also binds with the adopting helix. Consequently, MLL can facilitate pKID binding to the pKID-binding site by blocking the MLL-binding site. This also supports experimentally obtained results.

  10. Dosimetric evaluation of the interplay effect in respiratory-gated RapidArc radiation therapy

    International Nuclear Information System (INIS)

    Riley, Craig; Yang, Yong; Li, Tianfang; Zhang, Yongqian; Heron, Dwight E.; Huq, M. Saiful

    2014-01-01

    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

  11. Dosimetric evaluation of the interplay effect in respiratory-gated RapidArc radiation therapy.

    Science.gov (United States)

    Riley, Craig; Yang, Yong; Li, Tianfang; Zhang, Yongqian; Heron, Dwight E; Huq, M Saiful

    2014-01-01

    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. 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. 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 therapy. Varied results were

  12. Conformal radiotherapy: principles and classification

    International Nuclear Information System (INIS)

    Rosenwald, J.C.; Gaboriaud, G.; Pontvert, D.

    1999-01-01

    'Conformal radiotherapy' is the name fixed by usage and given to a new form of radiotherapy resulting from the technological improvements observed during the last ten years. While this terminology is now widely used, no precise definition can be found in the literature. Conformal radiotherapy refers to an approach in which the dose distribution is more closely 'conformed' or adapted to the actual shape of the target volume. However, the achievement of a consensus on a more specific definition is hampered by various difficulties, namely in characterizing the degree of 'conformality'. We have therefore suggested a classification scheme be established on the basis of the tools and the procedures actually used for all steps of the process, i.e., from prescription to treatment completion. Our classification consists of four levels: schematically, at level 0, there is no conformation (rectangular fields); at level 1, a simple conformation takes place, on the basis of conventional 2D imaging; at level 2, a 3D reconstruction of the structures is used for a more accurate conformation; and level 3 includes research and advanced dynamic techniques. We have used our personal experience, contacts with colleagues and data from the literature to analyze all the steps of the planning process, and to define the tools and procedures relevant to a given level. The corresponding tables have been discussed and approved at the European level within the Dynarad concerted action. It is proposed that the term 'conformal radiotherapy' be restricted to procedures where all steps are at least at level 2. (author)

  13. Conformational Dynamics of a Y-Family DNA Polymerase during Substrate Binding and Catalysis As Revealed by Interdomain F?rster Resonance Energy Transfer

    OpenAIRE

    Maxwell, Brian A.; Xu, Cuiling; Suo, Zucai

    2014-01-01

    Numerous kinetic, structural, and theoretical studies have established that DNA polymerases adjust their domain structures to enclose nucleotides in their active sites and then rearrange critical active site residues and substrates for catalysis, with the latter conformational change acting to kinetically limit the correct nucleotide incorporation rate. Additionally, structural studies have revealed a large conformational change between the apoprotein and the DNA?protein binary state for Y-fa...

  14. Conformal Killing horizons and their thermodynamics

    Science.gov (United States)

    Nielsen, Alex B.; Shoom, Andrey A.

    2018-05-01

    Certain dynamical black hole solutions can be mapped to static spacetimes by conformal metric transformations. This mapping provides a physical link between the conformal Killing horizon of the dynamical black hole and the Killing horizon of the static spacetime. Using the Vaidya spacetime as an example, we show how this conformal relation can be used to derive thermodynamic properties of such dynamical black holes. Although these horizons are defined quasi-locally and can be located by local experiments, they are distinct from other popular notions of quasi-local horizons such as apparent horizons. Thus in the dynamical Vaidya spacetime describing constant accretion of null dust, the conformal Killing horizon, which is null by construction, is the natural horizon to describe the black hole.

  15. Feasibility of Single-Isocenter Volumetric Modulated Arc Radiosurgery for Treatment of Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Clark, Grant M.; Popple, Richard A.; Young, P. Edward; Fiveash, John B.

    2010-01-01

    Purpose: To evaluate the relative plan quality of single-isocenter vs. multi-isocenter volumetric modulated arc therapy (VMAT) for radiosurgical treatment of multiple central nervous system metastases. Methods and Materials: VMAT plans were created using RapidArc technology for treatment of simulated patients with three brain metastases. The plans consisted of single-arc/single-isocenter, triple-arc (noncoplanar)/single-isocenter, and triple-arc (coplanar)/triple-isocenter configurations. All VMAT plans were normalized to deliver 100% of the 20-Gy prescription dose to all lesions. The plans were evaluated by calculation of Paddick and Radiation Therapy Oncology Group conformity index scores, Paddick gradient index scores, and 12-Gy isodose volumes. Results: All plans were judged clinically acceptable, but differences were observed in the dosimetric parameters, with the use of multiple noncoplanar arcs showing small improvements in the conformity indexes compared with the single-arc/single-isocenter and triple-arc (coplanar)/triple-isocenter plans. Multiple arc plans (triple-arc [noncoplanar]/single-isocenter and triple-arc [coplanar]/triple-isocenter) showed smaller 12-Gy isodose volumes in scenarios involving three metastases spaced closely together, with only small differences noted among all plans involving lesions spaced further apart. Conclusion: Our initial results suggest that single-isocenter VMAT plans can be used to deliver conformity equivalent to that of multiple isocenter VMAT techniques. For targets that are closely spaced, multiple noncoplanar single-isocenter arcs might be required. VMAT radiosurgery for multiple targets using a single isocenter can be efficiently delivered, requiring less than one-half the beam time required for multiple isocenter set ups. VMAT radiosurgery will likely replace multi-isocenter techniques for linear accelerator-based treatment of multiple targets.

  16. 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

  17. Tokamak ARC damage

    International Nuclear Information System (INIS)

    Murray, J.G.; Gorker, G.E.

    1985-01-01

    Tokamak fusion reactors will have large plasma currents of approximately 10 MA with hundreds of megajoules stored in the magnetic fields. When a major plasma instability occurs, the disruption of the plasma current induces voltage in the adjacent conducting structures, giving rise to large transient currents. The induced voltages may be sufficiently high to cause arcing across sector gaps or from one protruding component to another. This report reviews a tokamak arcing scenario and provides guidelines for designing tokamaks to minimize the possibility of arc damage

  18. Tokamak ARC damage

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J.G.; Gorker, G.E.

    1985-01-01

    Tokamak fusion reactors will have large plasma currents of approximately 10 MA with hundreds of megajoules stored in the magnetic fields. When a major plasma instability occurs, the disruption of the plasma current induces voltage in the adjacent conducting structures, giving rise to large transient currents. The induced voltages may be sufficiently high to cause arcing across sector gaps or from one protruding component to another. This report reviews a tokamak arcing scenario and provides guidelines for designing tokamaks to minimize the possibility of arc damage.

  19. Metal halide arc discharge lamp having short arc length

    Science.gov (United States)

    Muzeroll, Martin E. (Inventor)

    1994-01-01

    A metal halide arc discharge lamp includes a sealed light-transmissive outer jacket, a light-transmissive shroud located within the outer jacket and an arc tube assembly located within the shroud. The arc tube assembly includes an arc tube, electrodes mounted within the arc tube and a fill material for supporting an arc discharge. The electrodes have a spacing such that an electric field in a range of about 60 to 95 volts per centimeter is established between the electrodes. The diameter of the arc tube and the spacing of the electrodes are selected to provide an arc having an arc diameter to arc length ratio in a range of about 1.6 to 1.8. The fill material includes mercury, sodium iodide, scandium tri-iodide and a rare gas, and may include lithium iodide. The lamp exhibits a high color rendering index, high lumen output and high color temperature.

  20. 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.

  1. Numerical investigation of the double-arcing phenomenon in a cutting arc torch

    International Nuclear Information System (INIS)

    Mancinelli, B. R.; Minotti, F. O.; Kelly, H.; Prevosto, L.

    2014-01-01

    A numerical investigation of the double-arcing phenomenon in a cutting arc torch is reported. The dynamics of the double-arcing were simulated by using a two-dimensional model of the gas breakdown development in the space-charge layer contiguous to the nozzle of a cutting arc torch operated with oxygen. The kinetic scheme includes ionization of heavy particles by electron impact, electron attachment, electron detachment, electron–ion recombination, and ion–ion recombination. Complementary measurements during double-arcing phenomena were also conducted. A marked rise of the nozzle voltage was found. The numerical results showed that the dynamics of a cathode spot at the exit of the nozzle inner surface play a key role in the raising of the nozzle voltage, which in turn allows more electrons to return to the wall at the nozzle inlet. The return flow of electrons thus closes the current loop of the double-arcing. The increase in the (floating) nozzle voltage is due to the fact that the increased electron emission at the spot is mainly compensated by the displacement current (the ions do not play a relevant role due to its low-mobility) until that the stationary state is achieved and the electron return flow fully-compensates the electron emission at the spot. A fairly good agreement was found between the model and the experiment for a spot emission current growth rate of the order of 7 × 10 4  A/s.

  2. Arc plasma devices: Evolving mechanical design from numerical

    Indian Academy of Sciences (India)

    A recipe for obtaining mechanical design of arc plasma devices from numerical ... to the plasma of the mixture of molecular gases like nitrogen and oxygen. ... Temperature field, associated fluid dynamics and electrical characteristics of a ...

  3. Vacuum arc anode phenomena

    International Nuclear Information System (INIS)

    Miller, H.C.

    1976-01-01

    A brief review of anode phenomena in vacuum arcs is presented. Discussed in succession are: the transition of the arc into the anode spot mode; the temperature of the anode before, during and after the anode spot forms; and anode ions. Characteristically the anode spot has a temperature of the order of the atmospheric boiling point of the anode material and is a copious source of vapor and energetic ions. The dominant mechanism controlling the transition of the vacuum arc into the anode spot mode appears to depend upon the electrode geometry, the electrode material, and the current waveform of the particular vacuum arc being considered. Either magnetic constriction in the gap plasma or gross anode melting can trigger the transition; indeed, a combination of the two is a common cause of anode spot formation

  4. Filtered cathodic arc source

    International Nuclear Information System (INIS)

    Falabella, S.; Sanders, D.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 is described. 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. 3 figures

  5. Using arc voltage to locate the anode attachment in plasma arc cutting

    International Nuclear Information System (INIS)

    Osterhouse, D J; Heberlein, J V R; Lindsay, J W

    2013-01-01

    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. (paper)

  6. 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

    International Nuclear Information System (INIS)

    Yuen, Jasper; Rodrigues, George; Trenka, Kristina; Coad, Terry; Yartsev, Slav; D'Souza, David; Lock, Michael; Bauman, Glenn

    2008-01-01

    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. 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. When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p < 0.001), similar nodal coverage (8/8 t-test comparisons; p = ns), higher and more homogenous pelvic tissue dose (6/6 t-test comparisons; p < 0.03), at the cost of slightly higher critical structure dose (D dose , 1–3 Gy over 5/10 dose points; p < 0.03). The dIMRT/HT approaches were superior to 3DCRT in sparing organs at risk (22/24 t-test comparisons; p < 0.05). 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

  7. 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...... triggered by Townsend breakdown between the two legs of the gliding arc. The emission from the plasma column is shown to pulsate at a frequency of 62.5 kHz, i.e., twice the frequency of the AC power supply. Optical emission spectra of the plasma radiation show the presence of excited N2, NO and OH radicals...... suggesting that ground-state OH is not formed in the plasma column but in its vicinity. ©2013 Optical Society of America...

  8. 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...

  9. 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....

  10. Conformal Einstein spaces

    International Nuclear Information System (INIS)

    Kozameh, C.N.; Newman, E.T.; Tod, K.P.

    1985-01-01

    Conformal transformations in four-dimensional. In particular, a new set of two necessary and sufficient conditions for a space to be conformal to an Einstein space is presented. The first condition defines the class of spaces conformal to C spaces, whereas the last one (the vanishing of the Bach tensor) gives the particular subclass of C spaces which are conformally related to Einstein spaces. (author)

  11. Superspace conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Quella, Thomas [Koeln Univ. (Germany). Inst. fuer Theoretische Physik; Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-07-15

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  12. Superspace conformal field theory

    International Nuclear Information System (INIS)

    Quella, Thomas

    2013-07-01

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  13. Performance of Conformable Phenolic Impregnated Carbon Ablator in Aerothermal Environments

    Science.gov (United States)

    Thornton, Jeremy; Fan, Wendy; Stackpoole, Mairead; Kao, David; Skokova, Kristina; Chavez-Garcia, Jose

    2012-01-01

    Conformable Phenolic Impregnated Carbon Ablator, a cousin of Phenolic Impregnated Carbon Ablator (PICA), was developed at NASA Ames Research Center as a lightweight thermal protection system under the Fundamental Aeronautics Program. PICA is made using a brittle carbon substrate, which has a very low strain to failure. Conformable PICA is made using a flexible carbon substrate, a felt in this case. The flexible felt significantly increases the strain to failure of the ablator. PICA is limited by its thermal mechanical properties. Future NASA missions will require heatshields that are more fracture resistant than PICA and, as a result, NASA Ames is working to improve PICA's performance by developing conformable PICA to meet these needs. Research efforts include tailoring the chemistry of conformable PICA with varying amounts of additives to enhance mechanical properties and testing them in aerothermal environments. This poster shows the performance of conformable PICA variants in arc jets tests. Some mechanical and thermal properties will also be presented.

  14. ALICE-ARC integration

    International Nuclear Information System (INIS)

    Anderlik, C; Gregersen, A R; 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 module implementing the functionalities necessary to achieve AliEn job submission and management to ARC enabled sites

  15. SU-G-BRC-10: Feasibility of a Web-Based Monte Carlo Simulation Tool for Dynamic Electron Arc Radiotherapy (DEAR)

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, A; Wu, Q [Duke University Medical Center, Durham, NC (United States); Sawkey, D [Varian Medical Systems, Palo Alto, CA (United States)

    2016-06-15

    Purpose: DEAR is a radiation therapy technique utilizing synchronized motion of gantry and couch during delivery to optimize dose distribution homogeneity and penumbra for treatment of superficial disease. Dose calculation for DEAR is not yet supported by commercial TPSs. The purpose of this study is to demonstrate the feasibility of using a web-based Monte Carlo (MC) simulation tool (VirtuaLinac) to calculate dose distributions for a DEAR delivery. Methods: MC simulations were run through VirtuaLinac, which is based on the GEANT4 platform. VirtuaLinac utilizes detailed linac head geometry and material models, validated phase space files, and a voxelized phantom. The input was expanded to include an XML file for simulation of varying mechanical axes as a function of MU. A DEAR XML plan was generated and used in the MC simulation and delivered on a TrueBeam in Developer Mode. Radiographic film wrapped on a cylindrical phantom (12.5 cm radius) measured dose at a depth of 1.5 cm and compared to the simulation results. Results: A DEAR plan was simulated using an energy of 6 MeV and a 3×10 cm{sup 2} cut-out in a 15×15 cm{sup 2} applicator for a delivery of a 90° arc. The resulting data were found to provide qualitative and quantitative evidence that the simulation platform could be used as the basis for DEAR dose calculations. The resulting unwrapped 2D dose distributions agreed well in the cross-plane direction along the arc, with field sizes of 18.4 and 18.2 cm and penumbrae of 1.9 and 2.0 cm for measurements and simulations, respectively. Conclusion: Preliminary feasibility of a DEAR delivery using a web-based MC simulation platform has been demonstrated. This tool will benefit treatment planning for DEAR as a benchmark for developing other model based algorithms, allowing efficient optimization of trajectories, and quality assurance of plans without the need for extensive measurements.

  16. SU-G-BRC-10: Feasibility of a Web-Based Monte Carlo Simulation Tool for Dynamic Electron Arc Radiotherapy (DEAR)

    International Nuclear Information System (INIS)

    Rodrigues, A; Wu, Q; Sawkey, D

    2016-01-01

    Purpose: DEAR is a radiation therapy technique utilizing synchronized motion of gantry and couch during delivery to optimize dose distribution homogeneity and penumbra for treatment of superficial disease. Dose calculation for DEAR is not yet supported by commercial TPSs. The purpose of this study is to demonstrate the feasibility of using a web-based Monte Carlo (MC) simulation tool (VirtuaLinac) to calculate dose distributions for a DEAR delivery. Methods: MC simulations were run through VirtuaLinac, which is based on the GEANT4 platform. VirtuaLinac utilizes detailed linac head geometry and material models, validated phase space files, and a voxelized phantom. The input was expanded to include an XML file for simulation of varying mechanical axes as a function of MU. A DEAR XML plan was generated and used in the MC simulation and delivered on a TrueBeam in Developer Mode. Radiographic film wrapped on a cylindrical phantom (12.5 cm radius) measured dose at a depth of 1.5 cm and compared to the simulation results. Results: A DEAR plan was simulated using an energy of 6 MeV and a 3×10 cm 2 cut-out in a 15×15 cm 2 applicator for a delivery of a 90° arc. The resulting data were found to provide qualitative and quantitative evidence that the simulation platform could be used as the basis for DEAR dose calculations. The resulting unwrapped 2D dose distributions agreed well in the cross-plane direction along the arc, with field sizes of 18.4 and 18.2 cm and penumbrae of 1.9 and 2.0 cm for measurements and simulations, respectively. Conclusion: Preliminary feasibility of a DEAR delivery using a web-based MC simulation platform has been demonstrated. This tool will benefit treatment planning for DEAR as a benchmark for developing other model based algorithms, allowing efficient optimization of trajectories, and quality assurance of plans without the need for extensive measurements.

  17. Non-conformable, partial and conformable transposition

    DEFF Research Database (Denmark)

    König, Thomas; Mäder, Lars Kai

    2013-01-01

    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...... the transposition process. We therefore conclude that a stronger focus on an effective sanctioning mechanism is warranted for safeguarding compliance with directives....

  18. Conformal Aspects of QCD

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S

    2003-11-19

    Theoretical and phenomenological evidence is now accumulating that the QCD coupling becomes constant at small virtuality; i.e., {alpha}{sub s}(Q{sup 2}) develops an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. For example, the hadronic decays of the {tau} lepton can be used to determine the effective charge {alpha}{sub {tau}}(m{sub {tau}{prime}}{sup 2}) for a hypothetical {tau}-lepton with mass in the range 0 < m{sub {tau}{prime}} < m{sub {tau}}. The {tau} decay data at low mass scales indicates that the effective charge freezes at a value of s = m{sub {tau}{prime}}{sup 2} of order 1 GeV{sup 2} with a magnitude {alpha}{sub {tau}} {approx} 0.9 {+-} 0.1. The near-constant behavior of effective couplings suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer and why there are no significant running coupling corrections to quark counting rules for exclusive processes. The AdS/CFT correspondence of large N{sub c} supergravity theory in higher-dimensional anti-de Sitter space with supersymmetric QCD in 4-dimensional space-time also has interesting implications for hadron phenomenology in the conformal limit, including an all-orders demonstration of counting rules for exclusive processes and light-front wavefunctions. The utility of light-front quantization and light-front Fock wavefunctions for analyzing nonperturbative QCD and representing the dynamics of QCD bound states is also discussed.

  19. An approach for optimizing arc welding applications

    International Nuclear Information System (INIS)

    Chapuis, Julien

    2011-01-01

    The dynamic and transport mechanisms involved in the arc plasma and the weld pool of arc welding operations are numerous and strongly coupled. They produce a medium the magnitudes of which exhibit rapid time variations and very marked gradients which make any experimental analysis complex in this disrupted environment. In this work, we study the TIG and MIG processes. An experimental platform was developed to allow synchronized measurement of various physical quantities associated with welding (process parameters, temperatures, clamping forces, metal transfer, etc.). Numerical libraries dedicated to applied studies in arc welding are developed. They enable the treatment of a large flow of data (signals, images) with a systematic and global method. The advantages of this approach for the enrichment of numerical simulation and arc process control are shown in different situations. Finally, this experimental approach is used in the context of the chosen application to obtain rich measurements to describe the dynamic behavior of the weld pool in P-GMAW. Dimensional analysis of these experimental measurements allows to identify the predominant mechanisms involved and to determine experimentally the characteristic times associated. This type of approach includes better description of the behavior of a macro-drop of molten metal or the phenomena occurring in the humping instabilities. (author)

  20. Vacuum Arc Ion Sources

    CERN Document Server

    Brown, I.

    2013-12-16

    The vacuum arc ion source has evolved into a more or less standard laboratory tool for the production of high-current beams of metal ions, and is now used in a number of different embodiments at many laboratories around the world. Applications include primarily ion implantation for material surface modification research, and good performance has been obtained for the injection of high-current beams of heavy-metal ions, in particular uranium, into particle accelerators. As the use of the source has grown, so also have the operational characteristics been improved in a variety of different ways. Here we review the principles, design, and performance of vacuum arc ion sources.

  1. Tigers in the Terai: Strong evidence for meta-population dynamics contributing to tiger recovery and conservation in the Terai Arc Landscape.

    Directory of Open Access Journals (Sweden)

    Kanchan Thapa

    Full Text Available The source populations of tigers are mostly confined to protected areas, which are now becoming isolated. A landscape scale conservation strategy should strive to facilitate dispersal and survival of dispersing tigers by managing habitat corridors that enable tigers to traverse the matrix with minimal conflict. We present evidence for tiger dispersal along transboundary protected areas complexes in the Terai Arc Landscape, a priority tiger landscape in Nepal and India, by comparing camera trap data, and through population models applied to the long term camera trap data sets. The former showed that 11 individual tigers used the corridors that connected the transboundary protected areas. The estimated population growth rates using the minimum observed population size in two protected areas in Nepal, Bardia National Park and Suklaphanta National Park showed that the increases were higher than expected from growth rates due to in situ reproduction alone. These lines of evidence suggests that tigers are recolonizing Nepal's protected areas from India, after a period of population decline, and that the tiger populations in the transboundary protected areas complexes may be maintained as meta-population. Our results demonstrate the importance of adopting a landscape-scale approach to tiger conservation, especially to improve population recovery and long term population persistence.

  2. 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

    International Nuclear Information System (INIS)

    Huh, S; Lee, S; Dagan, R; Malyapa, R; Mendenhall, N; Mendenhall, W; Ho, M; Hough, D; Yam, M; Li, Z

    2014-01-01

    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

  3. 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...

  4. Electric contact arcing

    International Nuclear Information System (INIS)

    Cuthrell, R.E.

    1976-01-01

    Electrical contacts must function properly in many types of components used in nuclear weapon systems. Design, application, and testing of these components require detailed knowledge of chemical and physical phenomena associated with stockpile storage, stockpile testing, and operation. In the past, investigation of these phenomena has led to significant discoveries on the effects of surface contaminants, friction and wear, and the mechanics of closure on contact performance. A recent investigation of contact arcing phenomena which revealed that, preceding contact closure, arcs may occur at voltages lower than had been previously known is described. This discovery is important, since arcing may damage contacts, and repetitive testing of contacts performed as part of a quality assurance program might produce cumulative damage that would yield misleading life-test data and could prevent proper operation of the contacts at some time in the future. This damage can be avoided by determining the conditions under which arcing occurs, and ensuring that these conditions are avoided in contact testing

  5. 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.

  6. Circular arc structures

    KAUST Repository

    Bo, Pengbo; Pottmann, Helmut; Kilian, Martin; Wang, Wen Ping; Wallner, Johannes

    2011-01-01

    and connecting elements as well as repetition of costly parts. This paper proposes so-called circular arc structures as a means to faithfully realize freeform designs without giving up smooth appearance. In contrast to non-smooth meshes with straight edges where

  7. 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...

  8. Thermal Arc Spray Overview

    International Nuclear Information System (INIS)

    Malek, Muhamad Hafiz Abd; Saad, Nor Hayati; Abas, Sunhaji Kiyai; Shah, Noriyati Mohd

    2013-01-01

    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.

  9. THE ARC TRAIL

    African Journals Online (AJOL)

    INTRODUCTION. The project, carried out by the 1985 Conservation. Team at Durban Girls1 High School, consisted of three main aims- Awareness, Recreation and conservation, which were incorporated into the naming of the ARC trail. The trail is situated in suburban Durban where it was felt that it was important to ...

  10. ARC Software and Models

    Science.gov (United States)

    Archives RESEARCH ▼ Research Areas Ongoing Projects Completed Projects SOFTWARE CONTACT ▼ Primary Contacts Researchers External Link MLibrary Deep Blue Software Archive Most research conducted at the ARC produce software code and methodologies that are transferred to TARDEC and industry partners. These

  11. 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...

  12. Ecton mechanism of ion flow generation in vacuum arc

    CERN Document Server

    Mesyats, G A

    2001-01-01

    The basic characteristics of cathode plasma generation in vacuum arc (ion erosion, ion average charge) were studied from the point of an ecton model of a cathode spot in vacuum arc. The estimates of ion parameters obtained for a single cell of a cathode spot show qualitative conformity with the experimental data. One introduces the following mechanism of cathode plasma generation in vacuum arc. In case of explosion-like destruction of a cathode segment under the effect of the Joule heating the cathode matter changes sequentially its state: condensed one, nonideal and ideal plasma ones. During this change one observes formation of plasma charge composition and ion acceleration under the effect of plasma pressure gradient

  13. Proposition of a modification to the VAR process and its application in the consolidation of pressed zircaloy chips and the evaluation of the dynamical system of the electric arc; Proposicao de um processo alternativo a fusao via forno VAR para a consolidacao de cavacos prensados de zircaloy e estudo do sistema dinamico do arco eletrico

    Energy Technology Data Exchange (ETDEWEB)

    Mucsi, Cristiano Stefano

    2005-07-01

    The objective of this work is the investigation of a new process as an alternative to the Vacuum Arc Remelting technology in the consolidation of Zircaloy chips. A procedure is proposed for the recycling of primary Zircaloy scraps by means of a modified VAR furnace. The performed studies were made in order to optimise the low cost new devices added to existing VAR furnace prototype, find ideal operational conditions, evaluate data acquisition system and the electric arc dynamical system in order to made viable the automated control of the modified VAR prototype. A funnel-crucible special device was developed and installed in a VAR prototype furnace allowing ingots to be obtained from pressed chips. This indicated the viability of creation of a new process for the consolidation of Zircaloy chips. The voltage of the electric arc during the melting runs was digitally recorded allowing the evaluation of the electric arc dynamics by using the topological invariant of the system: correlation dimension and the higher Liapunov exponent. (author)

  14. Change in tectonic force inferred from basin subsidence: Implications for the dynamical aspects of back-arc rifting in the western Mediterranean

    NARCIS (Netherlands)

    Yamasaki, T.; Stephenson, R.A.

    2009-01-01

    A method has been developed that allows temporal changes in tectonic force during rift basin formation to be inferred from observed tectonic subsidence curves and has been applied to the Gulf of Lions (the Provençal Basin) and the Valencia Trough in order to gain some understanding of the dynamical

  15. Conformal manifolds: ODEs from OPEs

    Science.gov (United States)

    Behan, Connor

    2018-03-01

    The existence of an exactly marginal deformation in a conformal field theory is very special, but it is not well understood how this is reflected in the allowed dimensions and OPE coefficients of local operators. To shed light on this question, we compute perturbative corrections to several observables in an abstract CFT, starting with the beta function. This yields a sum rule that the theory must obey in order to be part of a conformal manifold. The set of constraints relating CFT data at different values of the coupling can in principle be written as a dynamical system that allows one to flow arbitrarily far. We begin the analysis of it by finding a simple form for the differential equations when the spacetime and theory space are both one-dimensional. A useful feature we can immediately observe is that our system makes it very difficult for level crossing to occur.

  16. Evaporative behavior of carbon with MPD Arc Jet

    Energy Technology Data Exchange (ETDEWEB)

    Sukegawa, Toshio; Madarame, Haruki; Okamoto, Koji [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab.

    1996-10-01

    Using the Magneto-Plasma-Dynamic Arc Jet (MPD Arc Jet) device, the plasma-material interaction during simulated plasma disruption was experimentally investigated. To clarify the effects of the evaporation, the isotropic graphite was used as a target. The thermal conductivity of the isotropic graphite was much higher than that of the pyrolytic graphite, resulting in smaller evaporation. The light intensity distribution during the simulated disruption for the isotropic graphite was quite different from that for the pyrolytic graphite. (author)

  17. Characterization of juvenile pyroclasts from the Kos Plateau Tuff (Aegean Arc): insights into the eruptive dynamics of a large rhyolitic eruption

    Science.gov (United States)

    Bouvet de Maisonneuve, Caroline; Bachmann, Olivier; Burgisser, Alain

    2009-08-01

    Silicic pumices formed during explosive volcanic eruptions are faithful recorders of the state of the magma in the conduit, close to or at the fragmentation level. We have characterized four types of pumices from the non-welded rhyolitic Kos Plateau Tuff, which erupted 161,000 years ago in the East Aegean Arc, Greece. The dominant type of pumice (>90 vol.%) shows highly elongated tubular vesicles. These tube pumices occur throughout the eruption. Less common pumice types include: (1) “frothy” pumice (highly porous with large, sub-rounded vesicles), which form 5-10 vol.% of the coarsest pyroclastic flow deposits, (2) dominantly “microvesicular” and systematically crystal-poor pumices, which are found in early erupted, fine-grained pyroclastic flow units, and are characterized by many small (<50 μm in diameter) vesicles and few mm-sized, irregular voids, (3) grey or banded pumices, indicating the interaction between the rhyolite and a more mafic magma, which are found throughout the eruption sequence and display highly irregular bubble shapes. Except for the grey-banded pumices, all three other types are compositionally identical and were generated synchronously as they are found in the same pyroclastic units. They, therefore, record different conditions in the volcanic conduit leading to variable bubble nucleation, growth and coalescence. A total of 74 pumice samples have been characterized using thin section observation, SEM imagery, porosimetry, and permeametry. We show that the four pumice types have distinct total and connected porosity, tortuosity and permeability. Grey-banded pumices show large variations in petrophysical characteristics as a response to mingling of two different magmas. The microvesicular, crystal-poor, pumices have a bimodal bubble size distribution, interpreted as reflecting an early heterogeneous bubble nucleation event followed by homogeneous bubble nucleation close to fragmentation. Finally, the significant differences in

  18. Feedback Linearization Based Arc Length Control for Gas Metal Arc Welding

    DEFF Research Database (Denmark)

    Thomsen, Jesper Sandberg

    2005-01-01

    a linear system to be controlled by linear state feedback control. The advantage of using a nonlinear approach as feedback linearization is the ability of this method to cope with nonlinearities and different operating points. However, the model describing the GMAW process is not exact, and therefore......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......, the cancellation of nonlinear terms might give rise to problems with respect to robustness. Robustness of the closed loop system is therefore nvestigated by simulation....

  19. Jumping Dynamics

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2013-01-01

    paradigm the physical scale and henceforth also the massive spectrum of the theory jump at the lower boundary of the conformal window. In particular we propose that a theory can suddenly jump from a Quantum Chromodynamics type spectrum, at the lower boundary of the conformal window, to a conformal one...... without particle interpretation. The jumping scenario, therefore, does not support a near-conformal dynamics of walking type. We will also discuss the impact of jumping dynamics on the construction of models of dynamical electroweak symmetry breaking....

  20. Volumetric-modulated arc therapy in postprostatectomy radiotherapy patients: A planning comparison study

    International Nuclear Information System (INIS)

    Forde, Elizabeth; Kneebone, Andrew; Bromley, Regina; Guo, Linxin; Hunt, Peter; Eade, Thomas

    2013-01-01

    The purpose of this study was to compare postprostatectomy planning for volumetric-modulated arc therapy (VMAT) with both single arc (SA) and double arcs (DA) against dynamic sliding window intensity-modulated radiotherapy (IMRT). Ten cases were planned with IMRT, SA VMAT, and DA VMAT. All cases were planned to achieve a minimum dose of 68 Gy to 95% of the planning target volume (PTV) and goals to limit rectal volume >40 Gy to 35% and >65 Gy to 17%, and bladder volumes >40 Gy to 50% and >65 Gy to 25%. Plans were averaged across the 10 patients and compared for mean dose, conformity, homogeneity, rectal and bladder doses, and monitor units. The mean dose to the clinical target volume and PTV was significantly higher (p<0.05) for SA compared with DA or IMRT. The homogeneity index was not significantly different: SA = 0.09; DA = 0.08; and IMRT = 0.07. The rectal V40 was lowest for the DA plan. The rectal V20 was significantly lower (p<0.05) for both the VMAT plans compared with IMRT. There were no significant differences for bladder V40 or rectal and bladder V65. The IMRT plans required 1400 MU compared with 745 for DA and 708 for SA. This study shows that for equivalent dose coverage, SA and DA VMAT plans result in higher mean doses to the clinical target volume and PTV. This greater dose heterogeneity is balanced by improved low-range rectal doses and halving of the monitor units

  1. Volumetric-modulated arc therapy in postprostatectomy radiotherapy patients: A planning comparison study

    Energy Technology Data Exchange (ETDEWEB)

    Forde, Elizabeth, E-mail: eforde@tcd.ie [Radiation Oncology Department, Northern Sydney Cancer Centre, St Leonards, New South Wales (Australia); Kneebone, Andrew [Radiation Oncology Department, Northern Sydney Cancer Centre, St Leonards, New South Wales (Australia); Northern Clinical School, University of Sydney, New South Wales (Australia); Bromley, Regina [Institute of Medical Physics, School of Physics, University of Sydney, New South Wales (Australia); Guo, Linxin; Hunt, Peter [Radiation Oncology Department, Northern Sydney Cancer Centre, St Leonards, New South Wales (Australia); Eade, Thomas [Radiation Oncology Department, Northern Sydney Cancer Centre, St Leonards, New South Wales (Australia); Northern Clinical School, University of Sydney, New South Wales (Australia)

    2013-10-01

    The purpose of this study was to compare postprostatectomy planning for volumetric-modulated arc therapy (VMAT) with both single arc (SA) and double arcs (DA) against dynamic sliding window intensity-modulated radiotherapy (IMRT). Ten cases were planned with IMRT, SA VMAT, and DA VMAT. All cases were planned to achieve a minimum dose of 68 Gy to 95% of the planning target volume (PTV) and goals to limit rectal volume >40 Gy to 35% and >65 Gy to 17%, and bladder volumes >40 Gy to 50% and >65 Gy to 25%. Plans were averaged across the 10 patients and compared for mean dose, conformity, homogeneity, rectal and bladder doses, and monitor units. The mean dose to the clinical target volume and PTV was significantly higher (p<0.05) for SA compared with DA or IMRT. The homogeneity index was not significantly different: SA = 0.09; DA = 0.08; and IMRT = 0.07. The rectal V40 was lowest for the DA plan. The rectal V20 was significantly lower (p<0.05) for both the VMAT plans compared with IMRT. There were no significant differences for bladder V40 or rectal and bladder V65. The IMRT plans required 1400 MU compared with 745 for DA and 708 for SA. This study shows that for equivalent dose coverage, SA and DA VMAT plans result in higher mean doses to the clinical target volume and PTV. This greater dose heterogeneity is balanced by improved low-range rectal doses and halving of the monitor units.

  2. Underwater plasma arc cutting

    International Nuclear Information System (INIS)

    Leautier, R.; Pilot, G.

    1991-01-01

    This report describes the work done to develop underwater plasma arc cutting techniques, to characterise aerosols from cutting operations on radioactive and non-radioactive work-pieces, and to develop suitable ventilation and filtration techniques. The work has been carried out in the framework of a contract between CEA-CEN Cadarache and the Commission of European Communities. Furthermore, this work has been carried out in close cooperation with CEA-CEN Saclay mainly for secondary emissions and radioactive analysis. The contract started in May 1986 and was completed in December 1988 by a supplementary agreement. This report has been compiled from several progress reports submitted during the work period, contains the main findings of the work and encloses the results of comparative tests on plasma arc cutting

  3. Induced quantum conformal gravity

    International Nuclear Information System (INIS)

    Novozhilov, Y.V.; Vassilevich, D.V.

    1988-11-01

    Quantum gravity is considered as induced by matter degrees of freedom and related to the symmetry breakdown in the low energy region of a non-Abelian gauge theory of fundamental fields. An effective action for quantum conformal gravity is derived where both the gravitational constant and conformal kinetic term are positive. Relation with induced classical gravity is established. (author). 15 refs

  4. Thickenings and conformal gravity

    Science.gov (United States)

    Lebrun, Claude

    1991-07-01

    A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M].

  5. Thickenings and conformal gravity

    Energy Technology Data Exchange (ETDEWEB)

    LeBrun, C. (State Univ. of New York, Stony Brook, NY (USA). Dept. of Mathematics)

    1991-07-01

    A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason (B-M). (orig.).

  6. Thickenings and conformal gravity

    International Nuclear Information System (INIS)

    LeBrun, C.

    1991-01-01

    A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M]. (orig.)

  7. Conformal transformations in superspace

    International Nuclear Information System (INIS)

    Dao Vong Duc

    1977-01-01

    The spinor extension of the conformal algebra is investigated. The transformation law of superfields under the conformal coordinate inversion R defined in the superspace is derived. Using R-technique, the superconformally covariant two-point and three-point correlation functions are found

  8. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  9. Comparative analysis of volumetric-modulated arc therapy and intensity-modulated radiotherapy for base of tongue cancer

    International Nuclear Information System (INIS)

    Nithya, L.; Arulraj, Kumar; Rathinamuthu, Sasikumar; Pandey, Manish Bhushan; Nambi Raj, N. Arunai

    2014-01-01

    The aim of this study was to compare the various dosimetric parameters of dynamic multileaf collimator (MLC) intensity modulated radiation therapy (IMRT) plans with volumetric modulated arc therapy (VMAT) plans for base of tongue cases. All plans were done in Monaco planning system for Elekta synergy linear accelerator with 80 MLC. IMRT plans were planned with nine stationary beams, and VMAT plans were done for 360° arc with single arc or dual arc. The dose to the planning target volumes (PTV) for 70, 63, and 56 Gy was compared. The dose to 95, 98, and 50% volume of PTV were analyzed. The homogeneity index (HI) and the conformity index (CI) of the PTV 70 were also analyzed. IMRT and VMAT plan showed similar dose coverage, HI, and CI. Maximum dose and dose to 1-cc volume of spinal cord, planning risk volume (PRV) cord, and brain stem were compared. IMRT plan and VMAT plan showed similar results except for the 1 cc of PRV cord that received slightly higher dose in VMAT plan. Mean dose and dose to 50% volume of right and left parotid glands were analyzed. VMAT plan gave better sparing of parotid glands than IMRT. In normal tissue dose analyses VMAT was better than IMRT. The number of monitor units (MU) required for delivering the good quality of the plan and the time required to deliver the plan for IMRT and VMAT were compared. The number of MUs for VMAT was higher than that of IMRT plans. However, the delivery time was reduced by a factor of two for VMAT compared with IMRT. VMAT plans yielded good quality of the plan compared with IMRT, resulting in reduced treatment time and improved efficiency for base of tongue cases. (author)

  10. Comparative analysis of volumetric-modulated arc therapy and intensity-modulated radiotherapy for base of tongue cancer

    Directory of Open Access Journals (Sweden)

    L Nithya

    2014-01-01

    Full Text Available The aim of this study was to compare the various dosimetric parameters of dynamic multileaf collimator (MLC intensity modulated radiation therapy (IMRT plans with volumetric modulated arc therapy (VMAT plans for base of tongue cases. All plans were done in Monaco planning system for Elekta synergy linear accelerator with 80 MLC. IMRT plans were planned with nine stationary beams, and VMAT plans were done for 360° arc with single arc or dual arc. The dose to the planning target volumes (PTV for 70, 63, and 56 Gy was compared. The dose to 95, 98, and 50% volume of PTV were analyzed. The homogeneity index (HI and the conformity index (CI of the PTV 70 were also analyzed. IMRT and VMAT plan showed similar dose coverage, HI, and CI. Maximum dose and dose to 1-cc volume of spinal cord, planning risk volume (PRV cord, and brain stem were compared. IMRT plan and VMAT plan showed similar results except for the 1 cc of PRV cord that received slightly higher dose in VMAT plan. Mean dose and dose to 50% volume of right and left parotid glands were analyzed. VMAT plan gave better sparing of parotid glands than IMRT. In normal tissue dose analyses VMAT was better than IMRT. The number of monitor units (MU required for delivering the good quality of the plan and the time required to deliver the plan for IMRT and VMAT were compared. The number of MUs for VMAT was higher than that of IMRT plans. However, the delivery time was reduced by a factor of two for VMAT compared with IMRT. VMAT plans yielded good quality of the plan compared with IMRT, resulting in reduced treatment time and improved efficiency for base of tongue cases.

  11. Arc cathode spots

    International Nuclear Information System (INIS)

    Schrade, H.O.

    1989-01-01

    Arc spots are usually highly unstable and jump statistically over the cathode surface. In a magnetic field parallel to the surface, preferably they move in the retrograde direction; i.e., opposite to the Lorentzian rule. If the field is inclined with respect to the surface, the spots drift away at a certain angle with respect to the proper retrograde direction (Robson drift motion). These well-known phenomena are explained by one stability theory

  12. An Efficient Null Model for Conformational Fluctuations in Proteins

    DEFF Research Database (Denmark)

    Harder, Tim Philipp; Borg, Mikael; Bottaro, Sandro

    2012-01-01

    Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often...... limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide...... on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins....

  13. Circular arc structures

    KAUST Repository

    Bo, Pengbo

    2011-07-01

    The most important guiding principle in computational methods for freeform architecture is the balance between cost efficiency on the one hand, and adherence to the design intent on the other. Key issues are the simplicity of supporting and connecting elements as well as repetition of costly parts. This paper proposes so-called circular arc structures as a means to faithfully realize freeform designs without giving up smooth appearance. In contrast to non-smooth meshes with straight edges where geometric complexity is concentrated in the nodes, we stay with smooth surfaces and rather distribute complexity in a uniform way by allowing edges in the shape of circular arcs. We are able to achieve the simplest possible shape of nodes without interfering with known panel optimization algorithms. We study remarkable special cases of circular arc structures which possess simple supporting elements or repetitive edges, we present the first global approximation method for principal patches, and we show an extension to volumetric structures for truly threedimensional designs. © 2011 ACM.

  14. Conformity index: A review

    International Nuclear Information System (INIS)

    Feuvret, Loic; Noel, Georges; Mazeron, Jean-Jacques; Bey, Pierre

    2006-01-01

    We present a critical analysis of the conformity indices described in the literature and an evaluation of their field of application. Three-dimensional conformal radiotherapy, with or without intensity modulation, is based on medical imaging techniques, three-dimensional dosimetry software, compression accessories, and verification procedures. It consists of delineating target volumes and critical healthy tissues to select the best combination of beams. This approach allows better adaptation of the isodose to the tumor volume, while limiting irradiation of healthy tissues. Tools must be developed to evaluate the quality of proposed treatment plans. Dosimetry software provides the dose distribution in each CT section and dose-volume histograms without really indicating the degree of conformity. The conformity index is a complementary tool that attributes a score to a treatment plan or that can compare several treatment plans for the same patient. The future of conformal index in everyday practice therefore remains unclear

  15. Conformal invariance in supergravity

    International Nuclear Information System (INIS)

    Bergshoeff, E.A.

    1983-01-01

    In this thesis the author explains the role of conformal invariance in supergravity. He presents the complete structure of extended conformal supergravity for N <= 4. The outline of this work is as follows. In chapter 2 he briefly summarizes the essential properties of supersymmetry and supergravity and indicates the use of conformal invariance in supergravity. The idea that the introduction of additional symmetry transformations can make clear the structure of a field theory is not reserved to supergravity only. By means of some simple examples it is shown in chapter 3 how one can always introduce additional gauge transformations in a theory of massive vector fields. Moreover it is shown how the gauge invariant formulation sometimes explains the quantum mechanical properties of the theory. In chapter 4 the author defines the conformal transformations and summarizes their main properties. He explains how these conformal transformations can be used to analyse the structure of gravity. The supersymmetric extension of these results is discussed in chapter 5. Here he describes as an example how N=1 supergravity can be reformulated in a conformally-invariant way. He also shows that beyond N=1 the gauge fields of the superconformal symmetries do not constitute an off-shell field representation of extended conformal supergravity. Therefore, in chapter 6, a systematic method to construct the off-shell formulation of all extended conformal supergravity theories with N <= 4 is developed. As an example he uses this method to construct N=1 conformal supergravity. Finally, in chapter 7 N=4 conformal supergravity is discussed. (Auth.)

  16. What can we learn from HF signal scattered from a discrete arc?

    Directory of Open Access Journals (Sweden)

    E. Séran

    2009-05-01

    Full Text Available We present observations of a discrete southward propagating arc which appeared in the mid-night sector at latitudes equatorward of main substorm activity. The arc observations were made simultaneously by the ALFA (Auroral Light Fine Analysis optical camera, the SuperDARN-CUTLASS HF radar and the Demeter satellite during a coordinated multi-instrumental campaign conducted at the KEOPS/ESRANGE site in December 2006. The SuperDARN HF signal which is often lost in the regions of strong electron precipitation yields in our case clear backscatter from an isolated arc of weak intensity. Consequently we are able to study arc dynamics, the formation of meso-scale irregularities of the electron density along the arc, compare the arc motion with the convection of surrounding plasma and discuss the contribution of ionospheric ions in the arc erosion and its propagation.

  17. SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

    Energy Technology Data Exchange (ETDEWEB)

    Silva, D; Salmon, H; Pavan, G; Nardi, S; Anderson, E; Fairbanks, L; Junior, J; Cursino, F; Colodette, K [GRUPO COI, Rio De Janeiro, Rio De Janeiro (Brazil)

    2014-06-01

    Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plans were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.

  18. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  19. Volumetric Modulated Arc Therapy (VMAT) Treatment Planning for Superficial Tumors

    International Nuclear Information System (INIS)

    Zacarias, Albert S.; Brown, Mellonie F.; Mills, Michael D.

    2010-01-01

    The physician's planning objective is often a uniform dose distribution throughout the planning target volume (PTV), including superficial PTVs on or near the surface of a patient's body. Varian's Eclipse treatment planning system uses a progressive resolution optimizer (PRO), version 8.2.23, for RapidArc dynamic multileaf collimator volumetric modulated arc therapy planning. Because the PRO is a fast optimizer, optimization convergence errors (OCEs) produce dose nonuniformity in the superficial area of the PTV. We present a postsurgical cranial case demonstrating the recursive method our clinic uses to produce RapidArc treatment plans. The initial RapidArc treatment plan generated using one 360 o arc resulted in substantial dose nonuniformity in the superficial section of the PTV. We demonstrate the use of multiple arcs to produce improved dose uniformity in this region. We also compare the results of this superficial dose compensation method to the results of a recursive method of dose correction that we developed in-house to correct optimization convergence errors in static intensity-modulated radiation therapy treatment plans. The results show that up to 4 arcs may be necessary to provide uniform dose to the surface of the PTV with the current version of the PRO.

  20. Conformal expansions and renormalons

    Energy Technology Data Exchange (ETDEWEB)

    Rathsman, J.

    2000-02-07

    The coefficients in perturbative expansions in gauge theories are factorially increasing, predominantly due to renormalons. This type of factorial increase is not expected in conformal theories. In QCD conformal relations between observables can be defined in the presence of a perturbative infrared fixed-point. Using the Banks-Zaks expansion the authors study the effect of the large-order behavior of the perturbative series on the conformal coefficients. The authors find that in general these coefficients become factorially increasing. However, when the factorial behavior genuinely originates in a renormalon integral, as implied by a postulated skeleton expansion, it does not affect the conformal coefficients. As a consequence, the conformal coefficients will indeed be free of renormalon divergence, in accordance with previous observations concerning the smallness of these coefficients for specific observables. The authors further show that the correspondence of the BLM method with the skeleton expansion implies a unique scale-setting procedure. The BLM coefficients can be interpreted as the conformal coefficients in the series relating the fixed-point value of the observable with that of the skeleton effective charge. Through the skeleton expansion the relevance of renormalon-free conformal coefficients extends to real-world QCD.

  1. Hybrid laser-arc welding

    DEFF Research Database (Denmark)

    Hybrid laser-arc welding (HLAW) is a combination of laser welding with arc welding that overcomes many of the shortfalls of both processes. This important book gives a comprehensive account of hybrid laser-arc welding technology and applications. The first part of the book reviews...... the characteristics of the process, including the properties of joints produced by hybrid laser-arc welding and ways of assessing weld quality. Part II discusses applications of the process to such metals as magnesium alloys, aluminium and steel as well as the use of hybrid laser-arc welding in such sectors as ship...... building and the automotive industry. With its distinguished editor and international team of contributors, Hybrid laser-arc welding, will be a valuable source of reference for all those using this important welding technology. Professor Flemming Ove Olsen works in the Department of Manufacturing...

  2. Conformally connected universes

    International Nuclear Information System (INIS)

    Cantor, M.; Piran, T.

    1983-01-01

    A well-known difficulty associated with the conformal method for the solution of the general relativistic Hamiltonian constraint is the appearance of an aphysical ''bag of gold'' singularity at the nodal surface of the conformal factor. This happens whenever the background Ricci scalar is too large. Using a simple model, it is demonstrated that some of these singular solutions do have a physical meaning, and that these can be considered as initial data for Universe containing black holes, which are connected, in a conformally nonsingular way with each other. The relation between the ADM mass and the horizon area in this solution supports the cosmic censorship conjecture. (author)

  3. Bioactive focus in conformational ensembles: a pluralistic approach

    Science.gov (United States)

    Habgood, Matthew

    2017-12-01

    Computational generation of conformational ensembles is key to contemporary drug design. Selecting the members of the ensemble that will approximate the conformation most likely to bind to a desired target (the bioactive conformation) is difficult, given that the potential energy usually used to generate and rank the ensemble is a notoriously poor discriminator between bioactive and non-bioactive conformations. In this study an approach to generating a focused ensemble is proposed in which each conformation is assigned multiple rankings based not just on potential energy but also on solvation energy, hydrophobic or hydrophilic interaction energy, radius of gyration, and on a statistical potential derived from Cambridge Structural Database data. The best ranked structures derived from each system are then assembled into a new ensemble that is shown to be better focused on bioactive conformations. This pluralistic approach is tested on ensembles generated by the Molecular Operating Environment's Low Mode Molecular Dynamics module, and by the Cambridge Crystallographic Data Centre's conformation generator software.

  4. Conformational Dynamics on the Extracellular Side of LeuT Controlled by Na+ and K+ Ions and the Protonation State of Glu(290)

    DEFF Research Database (Denmark)

    Khelashvili, George; Schmidt, Solveig Gaarde; Shi, Lei

    2016-01-01

    Na+ ions and substrate have left, and the transporter prepares for a new cycle. We compare the results with the consequences of binding Na+ in the same apo system. Analysis of >50-μs atomistic molecular dynamics and enhanced sampling trajectories of constructs with Glu290, either charged or neutral......Ions play key mechanistic roles in the gating dynamics of neurotransmitter:sodium symporters (NSSs). In recent microsecond scale molecular dynamics simulations of a complete model of the dopamine transporter, a NSS protein, we observed a partitioning of K+ ions from the intracellular side toward...... the unoccupied Na2 site of dopamine transporter following the release of the Na2-bound Na+. Here we evaluate with computational simulations and experimental measurements of ion affinities under corresponding conditions, the consequences of K+ binding in the Na2 site of LeuT, a bacterial homolog of NSS, when both...

  5. Evidence that polar cap arcs occur on open field lines

    International Nuclear Information System (INIS)

    Gussenhoven, M.S.; Hardy, D.A.; Rich, F.J.; Mullen, E.G.; Redus, R.H.

    1990-01-01

    The characteristics of polar cap arc occurrence are reviewed to show that the assumption of a closed magnetospheric magnetic field topology at very high latitudes when the IMF B z is strongly northward is difficult to reconcile with a wide variety of observational and theoretical considerations. In particular, we consider the implications of observations of particle entry for high and low energy electrons, magnetic flux conservation between the near and far tail, the time sequencing in polar cap arcs events, and the hemispherical differences in polar cap arc observations. These points can be explained either by excluding the need for a major topological magnetic field change from explanations of polar cap arc dynamics, or by assuming a long-tailed magnetosphere for all IMF orientations in which magnetic field lines eventually merge with solar wind field lines in either a smooth or a patchy fashion. (author)

  6. A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA

    Czech Academy of Sciences Publication Activity Database

    Lavery, R.; Zakrzewska, K.; Beveridge, D.; Bishop, T. C.; Case, D. A.; Cheatham III, T. E.; Dixit, S.; Jayaram, B.; Lankaš, Filip; Laughton, Ch.; Maddocks, J. H.; Michon, A.; Osman, R.; Orozco, M.; Pérez, A.; Singh, T.; Špačková, Naďa; Šponer, Jiří

    Roč. 38, č. 1 ( 2010 ), s. 299-313 ISSN 0305-1048 R&D Projects: GA MŠk(CZ) LC06030; GA AV ČR(CZ) IAA400040802; GA ČR GA203/09/1476; GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : B-DNA * molecular dynamics * sequence dependet structure and dynamics Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 7.836, year: 2010

  7. Correlation methods in cutting arcs

    Energy Technology Data Exchange (ETDEWEB)

    Prevosto, L; Kelly, H, E-mail: prevosto@waycom.com.ar [Grupo de Descargas Electricas, Departamento Ing. Electromecanica, Universidad Tecnologica Nacional, Regional Venado Tuerto, Laprida 651, Venado Tuerto (2600), Santa Fe (Argentina)

    2011-05-01

    The present work applies similarity theory to the plasma emanating from transferred arc, gas-vortex stabilized plasma cutting torches, to analyze the existing correlation between the arc temperature and the physical parameters of such torches. It has been found that the enthalpy number significantly influence the temperature of the electric arc. The obtained correlation shows an average deviation of 3% from the temperature data points. Such correlation can be used, for instance, to predict changes in the peak value of the arc temperature at the nozzle exit of a geometrically similar cutting torch due to changes in its operation parameters.

  8. Correlation methods in cutting arcs

    International Nuclear Information System (INIS)

    Prevosto, L; Kelly, H

    2011-01-01

    The present work applies similarity theory to the plasma emanating from transferred arc, gas-vortex stabilized plasma cutting torches, to analyze the existing correlation between the arc temperature and the physical parameters of such torches. It has been found that the enthalpy number significantly influence the temperature of the electric arc. The obtained correlation shows an average deviation of 3% from the temperature data points. Such correlation can be used, for instance, to predict changes in the peak value of the arc temperature at the nozzle exit of a geometrically similar cutting torch due to changes in its operation parameters.

  9. Image processing for the Advanced Radiographic Capability (ARC) at the National Ignition Facility

    Science.gov (United States)

    Leach, Richard R.; Awwal, Abdul A. S.; Lowe-Webb, Roger; Miller-Kamm, Victoria; Orth, Charles; Roberts, Randy; Wilhelmsen, Karl

    2016-09-01

    The Advance Radiographic Capability (ARC) at the National Ignition Facility (NIF) is a laser system that employs up to four petawatt (PW) lasers to produce a sequence of short-pulse kilo-Joule laser pulses with controllable delays that generate X-rays to provide backlighting for high-density internal confinement fusion (ICF) capsule targets. Multi-frame, hard-X-ray radiography of imploding NIF capsules is a capability which is critical to the success of NIF's missions. ARC is designed to employ up to eight backlighters with tens-of-picosecond temporal resolution, to record the dynamics and produce an X-ray "motion picture" of the compression and ignition of cryogenic deuterium-tritium targets. ARC will generate tens-of-picosecond temporal resolution during the critical phases of ICF shots. Additionally, ARC supports a variety of other high energy density experiments including fast ignition studies on NIF. The automated alignment image analysis algorithms use digital camera sensor images to direct ARC beams onto the tens-of-microns scale metal wires. This paper describes the ARC automatic alignment sequence throughout the laser chain from pulse initiation to target with an emphasis on the image processing algorithms that generate the crucial alignment positions for ARC. The image processing descriptions and flow diagrams detail the alignment control loops throughout the ARC laser chain beginning in the ARC high-contrast front end (HCAFE), on into the ARC main laser area, and ending in the ARC target area.

  10. Arc structure of the DAM Jupiter Emission

    International Nuclear Information System (INIS)

    Leblanc, Y.

    1981-01-01

    An analysis of the dynamic spectra of the Jovian DAM emission (1.3--40 MHz) has been made from Voyager data; it appears that the different Jovian 'sources' can be defined by spectral chaaracteristics, rather than by occurrence probability. The non-Io emission consists of two families: vertex early arcs (VEA) and vertex late arcs (VLA). These two families are superimposed at all longitudes, but one is always more intense than the other. The characterics of the two families are specified; in particular, it is shown that the VEA family is more stable in time than the VLA family. The Io-controlled emission consists of the four sources already known from the ground-based observations in addition to a new source (Io-A')sp, identified by its dynamic spectrum alone. All of the sources are partially superimposed on non-Io emission. The (Io-B)sp and (Io-A')sp sources are made up of low-curvature arcs having low-frequency limits above 5 MHz. The high-frequency limit of the (Io-B)sp source is strongly modulated by Io-phase. The (Io-A)sp source has a specturm similar to the non-Io VLA emission. The other two sources, (Io-C)sp and (Io-D)sp, are not structured into well-defined arcs. A comparsion is made between the occurrence of these sources in the Io-CML plane with the sources defined from ground observations by probability of occurrence. Local time effects are observed only in the non-Io emission when compared before and after encounter. Before encounter, the VEA family is very weak and the VLA family very intense. After encounter, the opposite effect is observed. The Io-controlled sources are not affected by these local time effects

  11. Gas tungsten arc welder

    International Nuclear Information System (INIS)

    Christiansen, D.W.; Brown, W.F.

    1984-01-01

    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 grinder, co-axial with the electrode, is provided in the enclosure for refurbishing the used electrode between welds. The specification also discloses means for loading of the cladding with fuel pellets and for placement of reflectors, gas capsules and end caps. Gravity feed conveyor and inerting means are also described. (author)

  12. Molecular dynamics study of the effect of GABU insert on the conformational behavior of the multiple antigen glycopeptides during the solid-phase synthesis

    Czech Academy of Sciences Publication Activity Database

    Vepřek, Pavel; Vondrášek, Jiří; Trnka, T.; Ježek, Jan

    2004-01-01

    Roč. 10, Supplement (2004), s. 233 ISSN 1075-2617. [International /3./ and European Peptide Symposium /28./. 05.09.2004-10.09.2004, Praha] Institutional research plan: CEZ:AV0Z4055905 Keywords : MAGs * dendrimer * molecular dynamics study Subject RIV: CE - Biochemistry

  13. Effect of the aminoacid composition of model α-helical peptides on the physical properties of lipid bilayers and peptide conformation: a molecular dynamics simulation

    Czech Academy of Sciences Publication Activity Database

    Melicherčík, Milan; Holúbeková, A.; Hianik, T.; Urban, J.

    2013-01-01

    Roč. 19, č. 11 (2013), s. 4723-4730 ISSN 1610-2940 Institutional support: RVO:67179843 Keywords : Bilayer lipid membranes * Helical peptides * Molecular dynamics simulations * Phase transitions Subject RIV: BO - Biophysics Impact factor: 1.867, year: 2013

  14. Conformable variational iteration method

    Directory of Open Access Journals (Sweden)

    Omer Acan

    2017-02-01

    Full Text Available In this study, we introduce the conformable variational iteration method based on new defined fractional derivative called conformable fractional derivative. This new method is applied two fractional order ordinary differential equations. To see how the solutions of this method, linear homogeneous and non-linear non-homogeneous fractional ordinary differential equations are selected. Obtained results are compared the exact solutions and their graphics are plotted to demonstrate efficiency and accuracy of the method.

  15. Delineating the conformal window

    DEFF Research Database (Denmark)

    Frandsen, Mads Toudal; Pickup, Thomas; Teper, Michael

    2011-01-01

    We identify and characterise the conformal window in gauge theories relevant for beyond the standard model building, e.g. Technicolour, using the criteria of metric confinement and causal analytic couplings, which are known to be consistent with the phase diagram of supersymmetric QCD from Seiberg...... duality. Using these criteria we find perturbation theory to be consistent throughout the predicted conformal window for several of these gauge theories and we discuss recent lattice results in the light of our findings....

  16. Attitude Control and Orbital Dynamics Challenges of Removing the First 3-Axis Stabilized Tracking and Data Relay Satellite from the Geosynchronous ARC

    Science.gov (United States)

    Benet, Charles A.; Hofman, Henry; Williams, Thomas E.; Olney, Dave; Zaleski, Ronald

    2011-01-01

    Launched on April 4, 1983 onboard STS 6 (Space Shuttle Challenger), the First Tracking and Data Relay Satellite (TDRS 1) was retired above the Geosynchronous Orbit (GEO) on June 27, 2010 after having provided real-time communications with a variety of low-orbiting spacecraft over a 26-year period. To meet NASA requirements limiting orbital debris 1, a team of experts was assembled to conduct an End-Of-Mission (EOM) procedure to raise the satellite 350 km above the GEO orbit. Following the orbit raising via conventional station change maneuvers, the team was confronted with having to deplete the remaining propellant and passivate all energy storage or generation sources. To accomplish these tasks within the time window, communications (telemetry and control links), electrical power, propulsion, and thermal constraints, a spacecraft originally designed as a three-axis stabilized satellite was turned into a spinner. This paper (a companion paper to Innovative Approach Enabled the Retirement of TDRS 1, paper # 1699, IEEE 2011 Aerospace Conference, March 5-12, 2011 sup 2) focuses on the challenges of maintaining an acceptable spinning dynamics, while repetitively firing thrusters. Also addressed are the effects of thruster firings on the orbit characteristics and how they were mitigated by a careful scheduling of the fuel depletion operations. Periodic thruster firings for spin rate adjustment, nutation damping, and precession of the momentum vector were also required in order to maintain effective communications with the satellite. All operations were thoroughly rehearsed and supported by simulations thus lending a high level of confidence in meeting the NASA EOM goals.

  17. Local supertwistors and N=2 conformal supergravity

    International Nuclear Information System (INIS)

    Merkulov, S.A.

    1989-01-01

    N = 2 sypersymmetric extension of the local twistor theory is formulated. A supertwistor superconnection determined by the superconformal structure of the base superspace is introduced on the bundle of N = 2 local supertwistors. It is proved that the Yang - Mills equations for this superconnection coincide exactly with the Bach equations describing the dynamics of N 2 conformal supergravity

  18. Total dural irradiation: RapidArc versus static-field IMRT: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Paul J., E-mail: paulj.kelly@hse.ie [Department of Radiation Oncology, Dana Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, MA (United States); Mannarino, Edward; Lewis, John Henry; Baldini, Elizabeth H.; Hacker, Fred L. [Department of Radiation Oncology, Dana Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, MA (United States)

    2012-07-01

    The purpose of this study was to compare conventional fixed-gantry angle intensity-modulated radiation therapy (IMRT) with RapidArc for total dural irradiation. We also hypothesize that target volume-individualized collimator angles may produce substantial normal tissue sparing when planning with RapidArc. Five-, 7-, and 9-field fixed-gantry angle sliding-window IMRT plans were generated for comparison with RapidArc plans. Optimization and normal tissue constraints were constant for all plans. All plans were normalized so that 95% of the planning target volume (PTV) received at least 100% of the dose. RapidArc was delivered using 350 Degree-Sign clockwise and counterclockwise arcs. Conventional collimator angles of 45 Degree-Sign and 315 Degree-Sign were compared with 90 Degree-Sign on both arcs. Dose prescription was 59.4 Gy in 33 fractions. PTV metrics used for comparison were coverage, V{sub 107}%, D1%, conformality index (CI{sub 95}%), and heterogeneity index (D{sub 5}%-D{sub 95}%). Brain dose, the main challenge of this case, was compared using D{sub 1}%, Dmean, and V{sub 5} Gy. Dose to optic chiasm, optic nerves, globes, and lenses was also compared. The use of unconventional collimator angles (90 Degree-Sign on both arcs) substantially reduced dose to normal brain. All plans achieved acceptable target coverage. Homogeneity was similar for RapidArc and 9-field IMRT plans. However, heterogeneity increased with decreasing number of IMRT fields, resulting in unacceptable hotspots within the brain. Conformality was marginally better with RapidArc relative to IMRT. Low dose to brain, as indicated by V5Gy, was comparable in all plans. Doses to organs at risk (OARs) showed no clinically meaningful differences. The number of monitor units was lower and delivery time was reduced with RapidArc. The case-individualized RapidArc plan compared favorably with the 9-field conventional IMRT plan. In view of lower monitor unit requirements and shorter delivery time, RapidArc