Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

PubMed Central

2013-01-01

Background Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Methods Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). Results From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Conclusion Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent topotecan chemotherapy significantly improved the PFS rate and the intracranial lesion control rate of patients with brain metastases from lung cancer, and no significant increases in side effects were observed. Based on these results, this treatment method is recommended for phase III clinical trial. PMID:24125485

Esophageal cancer: outcomes of surgery, neoadjuvant chemotherapy, and three-dimension conformal radiotherapy.

PubMed

Fréchette, Eric; Buck, David A; Kaplan, Brian J; Chung, Theodore D; Shaw, James E; Kachnic, Lisa A; Neifeld, James P

2004-08-01

Neoadjuvant chemotherapy and radiation are being utilized with increasing frequency in the multimodal treatment of esophageal cancer, although their effects on morbidity, mortality, and survival remain unclear. The objective of this study was to determine the outcome of multimodal treatment in patients with localized esophageal cancer treated at a single institution. Between 1995 and 2002, 118 patients underwent treatment for localized esophageal cancer, utilizing surgery alone, chemoradiation alone, or surgery following neoadjuvant chemoradiation. There was no statistically significant difference in morbidity, mortality, or length of stay between the patients who received multimodal therapy when compared to surgery alone. A surgical resection after down-staging was possible in 9 out of 28 patients (32%) with a clinically non-resectable tumor (T4 or M1a). Forty-seven percent of the patients who received neoadjuvant therapy had a complete pathologic response with a 3-year survival of 59% as compared to only 20 months in those patients who did not achieve a complete response (P = 0.037). Neoadjuvant chemotherapy administered concomitantly with conformal radiotherapy can be performed safely in the treatment of esophageal cancer, without increasing the operative morbidity, mortality, or length of stay. The higher complete response rates to neoadjuvant treatment (as compared to other reports) may be due to the use of three-dimensional conformal radiation therapy or the novel use of weekly carboplatin and paclitaxel. Copyright 2004 Wiley-Liss, Inc.

Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

PubMed

Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

2016-04-26

Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients.

Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

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

Leong, Trevor, E-mail: trevor.leong@petermac.or; Joon, Daryl Lim; Willis, David

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined,more » multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.« less

Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

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

Carosi, Alessandra, E-mail: alessandra.carosi@katamail.com; Ingrosso, Gianluca; Ponti, Elisabetta

2014-07-01

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular,more » we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V{sub 60} and V{sub 50} (p = 0.001) and in bladder V{sub 70} and V{sub 65} (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.« less

Entanglement entropy in Galilean conformal field theories and flat holography.

PubMed

Bagchi, Arjun; Basu, Rudranil; Grumiller, Daniel; Riegler, Max

2015-03-20

We present the analytical calculation of entanglement entropy for a class of two-dimensional field theories governed by the symmetries of the Galilean conformal algebra, thus providing a rare example of such an exact computation. These field theories are the putative holographic duals to theories of gravity in three-dimensional asymptotically flat spacetimes. We provide a check of our field theory answers by an analysis of geodesics. We also exploit the Chern-Simons formulation of three-dimensional gravity and adapt recent proposals of calculating entanglement entropy by Wilson lines in this context to find an independent confirmation of our results from holography.

Dose-per-fraction escalation of accelerated hypofractionated three-dimensional conformal radiotherapy in locally advanced non-small cell lung cancer.

PubMed

Kepka, Lucyna; Tyc-Szczepaniak, Dobromira; Bujko, Krzysztof

2009-07-01

To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy. The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC. Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PubMed

Belderbos, José S A; De Jaeger, Katrien; Heemsbergen, Wilma D; Seppenwoolde, Yvette; Baas, Paul; Boersma, Liesbeth J; Lebesque, Joos V

2003-02-01

To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.

Fast generation of three-dimensional computational boundary-conforming periodic grids of C-type. [for turbine blades and propellers

NASA Technical Reports Server (NTRS)

Dulikravich, D. S.

1982-01-01

A fast computer program, GRID3C, was developed to generate multilevel three dimensional, C type, periodic, boundary conforming grids for the calculation of realistic turbomachinery and propeller flow fields. The technique is based on two analytic functions that conformally map a cascade of semi-infinite slits to a cascade of doubly infinite strips on different Riemann sheets. Up to four consecutively refined three dimensional grids are automatically generated and permanently stored on four different computer tapes. Grid nonorthogonality is introduced by a separate coordinate shearing and stretching performed in each of three coordinate directions. The grids are easily clustered closer to the blade surface, the trailing and leading edges and the hub or shroud regions by changing appropriate input parameters. Hub and duct (or outer free boundary) have different axisymmetric shapes. A vortex sheet of arbitrary thickness emanating smoothly from the blade trailing edge is generated automatically by GRID3C. Blade cross sectional shape, chord length, twist angle, sweep angle, and dihedral angle can vary in an arbitrary smooth fashion in the spanwise direction.

SU-E-T-279: Realization of Three-Dimensional Conformal Dose Planning in Prostate Brachytherapy

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

Li, Z; Jiang, S; Yang, Z

2014-06-01

Purpose: Successful clinical treatment in prostate brachytherapy is largely dependent on the effectiveness of pre-surgery dose planning. Conventional dose planning method could hardly arrive at a satisfy result. In this abstract, a three-dimensional conformal localized dose planning method is put forward to ensure the accuracy and effectiveness of pre-implantation dose planning. Methods: Using Monte Carlo method, the pre-calculated 3-D dose map for single source is obtained. As for multiple seeds dose distribution, the maps are combined linearly to acquire the 3-D distribution. The 3-D dose distribution is exhibited in the form of isodose surface together with reconstructed 3-D organs groupmore » real-timely. Then it is possible to observe the dose exposure to target volume and normal tissues intuitively, thus achieving maximum dose irradiation to treatment target and minimum healthy tissues damage. In addition, the exfoliation display of different isodose surfaces can be realized applying multi-values contour extraction algorithm based on voxels. The needles could be displayed in the system by tracking the position of the implanted seeds in real time to conduct block research in optimizing insertion trajectory. Results: This study extends dose planning from two-dimensional to three-dimensional, realizing the three-dimensional conformal irradiation, which could eliminate the limitations of 2-D images and two-dimensional dose planning. A software platform is developed using VC++ and Visualization Toolkit (VTK) to perform dose planning. The 3-D model reconstruction time is within three seconds (on a Intel Core i5 PC). Block research could be conducted to avoid inaccurate insertion into sensitive organs or internal obstructions. Experiments on eight prostate cancer cases prove that this study could make the dose planning results more reasonable. Conclusion: The three-dimensional conformal dose planning method could improve the rationality of dose planning by safely reducing the large target margin and avoiding dose dead zones for prostate cancer treatment. 1) National Natural Science Foundation of People's Republic of China (No. 51175373); 2) New Century Educational Talents Plan of Chinese Education Ministry (NCET-10-0625); 3) Scientific and Technological Major Project, Tianjin (No. 12ZCDZSY10600)« less

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

Dirix, Piet, E-mail: piet.dirix@uzleuven.b; Vanstraelen, Bianca; Jorissen, Mark

Purpose: To evaluate clinical outcome and toxicity of postoperative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 2003 and 2008, 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Treatment outcome and toxicity were retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation, from 1992 tomore » 2002. Results: Median follow-up was 30 months (range, 4-74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02). No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome. Conclusions: Postoperative IMRT for sinonasal cancer significantly improves disease-free survival and reduces acute as well as late toxicity. Consequently, IMRT should be considered the standard treatment modality for malignancies of the nasal cavity and paranasal sinuses.« less

Birkhoff theorem and conformal Killing-Yano tensors

NASA Astrophysics Data System (ADS)

Ferrando, Joan Josep; Sáez, Juan Antonio

2015-06-01

We analyze the main geometric conditions imposed by the hypothesis of the Jebsen-Birkhoff theorem. We show that the result (existence of an additional Killing vector) does not necessarily require a three-dimensional isometry group on two-dimensional orbits but only the existence of a conformal Killing-Yano tensor. In this approach the (additional) isometry appears as the known invariant Killing vector that the -metrics admit.

Three-dimensional boron particle loaded thermal neutron detector

DOEpatents

Nikolic, Rebecca J.; Conway, Adam M.; Graff, Robert T.; Kuntz, Joshua D.; Reinhardt, Catherine; Voss, Lars F.; Cheung, Chin Li; Heineck, Daniel

2014-09-09

Three-dimensional boron particle loaded thermal neutron detectors utilize neutron sensitive conversion materials in the form of nano-powders and micro-sized particles, as opposed to thin films, suspensions, paraffin, etc. More specifically, methods to infiltrate, intersperse and embed the neutron nano-powders to form two-dimensional and/or three-dimensional charge sensitive platforms are specified. The use of nano-powders enables conformal contact with the entire charge-collecting structure regardless of its shape or configuration.

Inverse planning in three-dimensional conformal and intensity-modulated radiotherapy of mid-thoracic oesophageal cancer.

PubMed

Wu, V W C; Sham, J S T; Kwong, D L W

2004-07-01

The aim of this study is to demonstrate the use of inverse planning in three-dimensional conformal radiation therapy (3DCRT) of oesophageal cancer patients and to evaluate its dosimetric results by comparing them with forward planning of 3DCRT and inverse planning of intensity-modulated radiotherapy (IMRT). For each of the 15 oesophageal cancer patients in this study, the forward 3DCRT, inverse 3DCRT and inverse IMRT plans were produced using the FOCUS treatment planning system. The dosimetric results and the planner's time associated with each of the treatment plans were recorded for comparison. The inverse 3DCRT plans showed similar dosimetric results to the forward plans in the planning target volume (PTV) and organs at risk (OARs). However, they were inferior to that of the IMRT plans in terms of tumour control probability and target dose conformity. Furthermore, the inverse 3DCRT plans were less effective in reducing the percentage lung volume receiving a dose below 25 Gy when compared with the IMRT plans. The inverse 3DCRT plans delivered a similar heart dose as in the forward plans, but higher dose than the IMRT plans. The inverse 3DCRT plans significantly reduced the operator's time by 2.5 fold relative to the forward plans. In conclusion, inverse planning for 3DCRT is a reasonable alternative to the forward planning for oesophageal cancer patients with reduction of the operator's time. However, IMRT has the better potential to allow further dose escalation and improvement of tumour control.

Grain Boundary Conformed Volumetric Mesh Generation from a Three-Dimensional Voxellated Polycrystalline Microstructure

NASA Astrophysics Data System (ADS)

Lee, Myeong-Jin; Jeon, Young-Ju; Son, Ga-Eun; Sung, Sihwa; Kim, Ju-Young; Han, Heung Nam; Cho, Soo Gyeong; Jung, Sang-Hyun; Lee, Sukbin

2018-07-01

We present a new comprehensive scheme for generating grain boundary conformed, volumetric mesh elements from a three-dimensional voxellated polycrystalline microstructure. From the voxellated image of a polycrystalline microstructure obtained from the Monte Carlo Potts model in the context of isotropic normal grain growth simulation, its grain boundary network is approximated as a curvature-maintained conformal triangular surface mesh using a set of in-house codes. In order to improve the surface mesh quality and to adjust mesh resolution, various re-meshing techniques in a commercial software are applied to the approximated grain boundary mesh. It is found that the aspect ratio, the minimum angle and the Jacobian value of the re-meshed surface triangular mesh are successfully improved. Using such an enhanced surface mesh, conformal volumetric tetrahedral elements of the polycrystalline microstructure are created using a commercial software, again. The resultant mesh seamlessly retains the short- and long-range curvature of grain boundaries and junctions as well as the realistic morphology of the grains inside the polycrystal. It is noted that the proposed scheme is the first to successfully generate three-dimensional mesh elements for polycrystals with high enough quality to be used for the microstructure-based finite element analysis, while the realistic characteristics of grain boundaries and grains are maintained from the corresponding voxellated microstructure image.

Grain Boundary Conformed Volumetric Mesh Generation from a Three-Dimensional Voxellated Polycrystalline Microstructure

NASA Astrophysics Data System (ADS)

Lee, Myeong-Jin; Jeon, Young-Ju; Son, Ga-Eun; Sung, Sihwa; Kim, Ju-Young; Han, Heung Nam; Cho, Soo Gyeong; Jung, Sang-Hyun; Lee, Sukbin

2018-03-01

We present a new comprehensive scheme for generating grain boundary conformed, volumetric mesh elements from a three-dimensional voxellated polycrystalline microstructure. From the voxellated image of a polycrystalline microstructure obtained from the Monte Carlo Potts model in the context of isotropic normal grain growth simulation, its grain boundary network is approximated as a curvature-maintained conformal triangular surface mesh using a set of in-house codes. In order to improve the surface mesh quality and to adjust mesh resolution, various re-meshing techniques in a commercial software are applied to the approximated grain boundary mesh. It is found that the aspect ratio, the minimum angle and the Jacobian value of the re-meshed surface triangular mesh are successfully improved. Using such an enhanced surface mesh, conformal volumetric tetrahedral elements of the polycrystalline microstructure are created using a commercial software, again. The resultant mesh seamlessly retains the short- and long-range curvature of grain boundaries and junctions as well as the realistic morphology of the grains inside the polycrystal. It is noted that the proposed scheme is the first to successfully generate three-dimensional mesh elements for polycrystals with high enough quality to be used for the microstructure-based finite element analysis, while the realistic characteristics of grain boundaries and grains are maintained from the corresponding voxellated microstructure image.

Definition of the supraclavicular and infraclavicular nodes: implications for three-dimensional CT-based conformal radiation therapy.

PubMed

Madu, C N; Quint, D J; Normolle, D P; Marsh, R B; Wang, E Y; Pierce, L J

2001-11-01

To delineate with computed tomography (CT) the anatomic regions containing the supraclavicular (SCV) and infraclavicular (IFV) nodal groups, to define the course of the brachial plexus, to estimate the actual radiation dose received by these regions in a series of patients treated in the traditional manner, and to compare these doses to those received with an optimized dosimetric technique. Twenty patients underwent contrast material-enhanced CT for the purpose of radiation therapy planning. CT scans were used to study the location of the SCV and IFV nodal regions by using outlining of readily identifiable anatomic structures that define the nodal groups. The brachial plexus was also outlined by using similar methods. Radiation therapy doses to the SCV and IFV were then estimated by using traditional dose calculations and optimized planning. A repeated measures analysis of covariance was used to compare the SCV and IFV depths and to compare the doses achieved with the traditional and optimized methods. Coverage by the 90% isodose surface was significantly decreased with traditional planning versus conformal planning as the depth to the SCV nodes increased (P < .001). Significantly decreased coverage by using the 90% isodose surface was demonstrated for traditional planning versus conformal planning with increasing IFV depth (P = .015). A linear correlation was found between brachial plexus depth and SCV depth up to 7 cm. Conformal optimized planning provided improved dosimetric coverage compared with standard techniques.

Probing RNA Native Conformational Ensembles with Structural Constraints.

PubMed

Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

2016-05-01

Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.

Dosimetric Comparison of Involved-Field Three-Dimensional Conformal Photon Radiotherapy and Breast-Sparing Proton Therapy for the Treatment of Hodgkin's Lymphoma in Female Pediatric Patients

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

Andolino, David L., E-mail: dandolin@iupui.edu; Hoene, Ted; Xiao, Lu

2011-11-15

Purpose: To assess the potential reduction in breast dose for young girls with Hodgkin's lymphoma (HL) treated with breast-sparing proton therapy (BS-PT) as compared with three-dimensional conformal involved-field photon radiotherapy (3D-CRT). Methods and Materials: The Clarian Health Cancer Registry was queried for female pediatric patients with the diagnosis of HL who received radiotherapy at the Indiana University Simon Cancer Center during 2006-2009. The original CT simulation images were obtained, and 3D-CRT and BS-PT plans delivering 21 Gy or cobalt gray equivalent (CGE) in 14 fractions were created for each patient. Dose-volume histogram data were collected for both 3D-CRT and BS-PTmore » plans and compared by paired t test for correlated samples. Results: The cancer registry provided 10 female patients with Ann Arbor Stage II HL, aged 10-18 years at the time of treatment. Both mean and maximum breast dose were significantly less with BS-PT compared with 3D-CRT: 0.95 CGE vs. 4.70 Gy (p < 0.001) and 21.07 CGE vs. 23.11 Gy (p < 0.001), respectively. The volume of breast receiving 1.0 Gy/CGE and 5.0 Gy/CGE was also significantly less with BS-PT, 194 cm{sup 3} and 93 cm{sup 3}, respectively, compared with 790 cm{sup 3} and 360 cm{sup 3} with 3D-CRT (p = 0.009, 0.013). Conclusion: Breast-sparing proton therapy has the potential to reduce unnecessary breast dose in young girls with HL by as much as 80% relative to involved-field 3D-CRT.« less

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: a prospective phase I/II study.

PubMed

Wu, Kai-Liang; Chen, Guei-Yuan; Xu, Zhi-Yong; Fu, Xiao-Long; Qian, Hao; Jiang, Guo-Liang

2009-12-01

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC). Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy. Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively. Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.

Stereoscopic Projection in Organic Chemistry: Bridging the Gap between Two and Three Dimensions.

ERIC Educational Resources Information Center

Rozzelle, Arlene A.; Rosenfeld, Stuart M.

1985-01-01

Shows how to make stereo slides of three-dimensional molecular models. The slides have been used to teach chirality, conformational isomerism, how models and two-dimensional representations embody selected aspects of structure, and fundamentals of using the specific model set required in a particular organic chemistry course. (JN)

Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy and 3-dimensional, conformal, accelerated radiotherapy in locally advanced nonsmall cell lung cancer.

PubMed

Rojas, Ana M; Lyn, Basil E; Wilson, Elena M; Williams, Frances J; Shah, Nihal; Dickson, Jeanette; Saunders, Michele I

2006-09-15

The objective of this study was to evaluate prospectively the acute and late adverse effects of taxane/carboplatin neoadjuvant chemotherapy and 3-dimensional, conformal radiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). Forty-two patients were entered into a nonrandomized Phase II study of continuous, hyperfractionated, accelerated radiotherapy (CHART) week-end less (CHARTWEL) to a dose of 60 grays (Gy). Three cycles of chemotherapy were given over 9 weeks before radiotherapy. Dose escalation with paclitaxel was from 150 mg/m2 to 225 mg/m2. Systemic toxicity to chemotherapy was monitored throughout. Radiation-induced, early, adverse effects were assessed during the first 9 weeks from the start of radiotherapy, and late effects were assessed from 3 months onward. Overall survival, disease-free survival, and locoregional tumor control also were monitored. Twenty percent of patients failed to receive chemotherapy as planned, primarily because of neutropenia. The incidence of Dische Dictionary Grade >or=2 and Grade >or=3 dysphagia was 57.5% and 10%, respectively, with an average duration of 1.2 weeks and 1.5 days, respectively. By 9 weeks, <3% of patients were symptomatic; and, eventually, all acute reactions were healed, and there has been no evidence of consequential damage. At 6 months, the actuarial incidence of moderate-to-severe pneumonitis was 10%. During this time, all patients were free of severe pulmonary complications. Actuarial estimates of Grade >or=2 late lung dysfunction were 3% at 1 year, 10% at 2 years, and remained at this level thereafter. The actuarial 3-year locoregional control and overall survival rates were 54% and 45%, respectively. Neoadjuvant chemotherapy followed by 3-dimensional, conformal CHARTWEL 60-Gy radiotherapy in patients with advanced NSCLC was feasible and was tolerated well. Historic comparisons indicated that locoregional tumor control is not compromised by the use of conformal techniques. (c) 2006 American Cancer Society.

Three Dimensional Sector Design with Optimal Number of Sectors

NASA Technical Reports Server (NTRS)

Xue, Min

2010-01-01

In the national airspace system, sectors get overloaded due to high traffic demand and inefficient airspace designs. Overloads can be eliminated in some cases by redesigning sector boundaries. This paper extends the Voronoi-based sector design method by automatically selecting the number of sectors, allowing three-dimensional partitions, and enforcing traffic pattern conformance. The method was used to design sectors at Fort-Worth and Indianapolis centers for current traffic scenarios. Results show that new designs can eliminate overloaded sectors, although not in all cases, reduce the number of necessary sectors, and conform to major traffic patterns. Overall, the new methodology produces enhanced and efficient sector designs.

Dual exposure, two-photon, conformal phasemask lithography for three dimensional silicon inverse woodpile photonic crystals

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

Shir, Daniel J.; Nelson, Erik C.; Chanda, Debashis

2010-01-01

The authors describe the fabrication and characterization of three dimensional silicon inverse woodpile photonic crystals. A dual exposure, two-photon, conformal phasemask technique is used to create high quality polymer woodpile structures over large areas with geometries that quantitatively match expectations based on optical simulations. Depositing silicon into these templates followed by the removal of the polymer results in silicon inverse woodpile photonic crystals for which calculations indicate a wide, complete photonic bandgap over a range of structural fill fractions. Spectroscopic measurements of normal incidence reflection from both the polymer and siliconphotonic crystals reveal good optical properties.

Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation.

PubMed

Ji, Kai; Zhao, Lujun; Yang, Chengwen; Meng, Maobin; Wang, Ping

2012-11-27

To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC) patients with a dose of 60 Gy/30f. Thirty-nine patients with medically inoperable T1-4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT) with involved-field radiation (IFI). The conformal clinical target volume (CTV) was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV) and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED) guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD) and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Under a 60 Gy dosage, the median D mean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40 Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions.

Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

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

Sekine, Ikuo, E-mail: isekine@ncc.go.jp; Sumi, Minako; Ito, Yoshinori

Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of themore » 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.« less

Reconfigurable Three-Dimensional Gold Nanorod Plasmonic Nanostructures Organized on DNA Origami Tripod.

PubMed

Zhan, Pengfei; Dutta, Palash K; Wang, Pengfei; Song, Gang; Dai, Mingjie; Zhao, Shu-Xia; Wang, Zhen-Gang; Yin, Peng; Zhang, Wei; Ding, Baoquan; Ke, Yonggang

2017-02-28

Distinct electromagnetic properties can emerge from the three-dimensional (3D) configuration of a plasmonic nanostructure. Furthermore, the reconfiguration of a dynamic plasmonic nanostructure, driven by physical or chemical stimuli, may generate a tailored plasmonic response. In this work, we constructed a 3D reconfigurable plasmonic nanostructure with controllable, reversible conformational transformation using bottom-up DNA self-assembly. Three gold nanorods (AuNRs) were positioned onto a reconfigurable DNA origami tripod. The internanorod angle and distance were precisely tuned through operating the origami tripod by toehold-mediated strand displacement. The transduction of conformational change manifested into a controlled shift of the plasmonic resonance peak, which was studied by dark-field microscopy, and agrees well with electrodynamic calculations. This new 3D plasmonic nanostructure not only provides a method to study the plasmonic resonance of AuNRs at prescribed 3D conformations but also demonstrates that DNA origami can serve as a general self-assembly platform for constructing various 3D reconfigurable plasmonic nanostructures with customized optical properties.

Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

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

Kharofa, Jordan; Choong, Nicholas; Wang, Dian

Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformalmore » RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54%, 31%, and 20% respectively. Conclusions: Continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin has an acceptable toxicity profile and offers a potentially curative option in a subset of patients with few other options.« less

Clinical Application of a Hybrid RapidArc Radiotherapy Technique for Locally Advanced Lung Cancer.

PubMed

Silva, Scott R; Surucu, Murat; Steber, Jennifer; Harkenrider, Matthew M; Choi, Mehee

2017-04-01

Radiation treatment planning for locally advanced lung cancer can be technically challenging, as delivery of ≥60 Gy to large volumes with concurrent chemotherapy is often associated with significant risk of normal tissue toxicity. We clinically implemented a novel hybrid RapidArc technique in patients with lung cancer and compared these plans with 3-dimensional conformal radiotherapy and RapidArc-only plans. Hybrid RapidArc was used to treat 11 patients with locally advanced lung cancer having bulky mediastinal adenopathy. All 11 patients received concurrent chemotherapy. All underwent a 4-dimensional computed tomography planning scan. Hybrid RapidArc plans concurrently combined static (60%) and RapidArc (40%) beams. All cases were replanned using 3- to 5-field 3-dimensional conformal radiotherapy and RapidArc technique as controls. Significant reductions in dose were observed in hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans for total lung V20 and mean (-2% and -0.6 Gy); contralateral lung mean (-2.92 Gy); and esophagus V60 and mean (-16.0% and -2.2 Gy; all P < .05). Contralateral lung doses were significantly lower for hybrid RapidArc plans compared to RapidArc-only plans (all P < .05). Compared to 3-dimensional conformal radiotherapy, heart V60 and mean dose were significantly improved with hybrid RapidArc (3% vs 5%, P = .04 and 16.32 Gy vs 16.65 Gy, P = .03). However, heart V40 and V45 and maximum spinal cord dose were significantly lower with RapidArc plans compared to hybrid RapidArc plans. Conformity and homogeneity were significantly better with hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans ( P < .05). Treatment was well tolerated, with no grade 3+ toxicities. To our knowledge, this is the first report on the clinical application of hybrid RapidArc in patients with locally advanced lung cancer. Hybrid RapidArc permitted safe delivery of 60 to 66 Gy to large lung tumors with concurrent chemotherapy and demonstrated advantages for reduction in low-dose lung volumes, esophageal dose, and mean heart dose.

Generalizing the bms3 and 2D-conformal algebras by expanding the Virasoro algebra

NASA Astrophysics Data System (ADS)

Caroca, Ricardo; Concha, Patrick; Rodríguez, Evelyn; Salgado-Rebolledo, Patricio

2018-03-01

By means of the Lie algebra expansion method, the centrally extended conformal algebra in two dimensions and the bms3 algebra are obtained from the Virasoro algebra. We extend this result to construct new families of expanded Virasoro algebras that turn out to be infinite-dimensional lifts of the so-called Bk, Ck and Dk algebras recently introduced in the literature in the context of (super)gravity. We also show how some of these new infinite-dimensional symmetries can be obtained from expanded Kač-Moody algebras using modified Sugawara constructions. Applications in the context of three-dimensional gravity are briefly discussed.

Conformational Sampling in Template-Free Protein Loop Structure Modeling: An Overview

PubMed Central

Li, Yaohang

2013-01-01

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a “mini protein folding problem” under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized. PMID:24688696

Conformational sampling in template-free protein loop structure modeling: an overview.

PubMed

Li, Yaohang

2013-01-01

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a "mini protein folding problem" under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized.

GRID3O- FAST GENERATION OF MULTILEVEL, THREE-DIMENSIONAL BOUNDARY-CONFORMING O-TYPE COMPUTATIONAL GRIDS

NASA Technical Reports Server (NTRS)

Dulikravich, D. S.

1994-01-01

A fast algorithm has been developed for accurately generating boundary-conforming, three-dimensional consecutively refined computational grids applicable to arbitrary wing-body and axial turbomachinery geometries. This algorithm has been incorporated into the GRID3O computer program. The method employed in GRID3O is based on using an analytic function to generate two-dimensional grids on a number of coaxial axisymmetric surfaces positioned between the centerbody and the outer radial boundary. These grids are of the O-type and are characterized by quasi-orthogonality, geometric periodicity, and an adequate resolution throughout the flow field. Because the built-in nonorthogonal coordinate stretching and shearing cause the grid lines leaving the blade or wing trailing-edge to end at downstream infinity, use of the generated grid simplifies the numerical treatment of three-dimensional trailing vortex sheets. The GRID3O program is written in FORTRAN IV for batch execution and has been implemented on an IBM 370 series computer with a central memory requirement of approximately 450K of 8 bit bytes. The GRID3O program was developed in 1981.

Comparison of three-dimensional vs. conventional radiotherapy in saving optic tract in paranasal sinus tumors.

PubMed

Kamian, S; Kazemian, A; Esfahani, M; Mohammadi, E; Aghili, M

2010-01-01

To assess the possibility of delivering a homogeneous irradiation with respect to maximal tolerated dose to the optic pathway for paranasal sinus (PNS) tumors. Treatment planning with conformal three-dimensional (3D) and conventional two-dimensional (2D) was done on CT scans of 20 patients who had early or advanced PNS tumors. Four cases had been previously irradiated. Dose-volume histograms (DVH) for the planning target volume (PTV) and the visual pathway including globes, chiasma and optic nerves were compared between the 2 treatment plannings. The area under curve (AUC) in the DVH of the globes on the same side and contralateral side of tumor involvement was significantly higher in 2D planning (p <0.05), which caused higher integral dose to both globes. Also, the AUC in the DVH of chiasma was higher in 2D treatment planning (p=0.002). The integral dose to the contralateral optic nerve was significantly lower with 3D planning (p=0.007), but there was no significant difference for the optic nerve which was on the same side of tumor involvement (p >0.05). The AUC in the DVH of PTV was not significant (201.1 + or - 16.23 mm(3) in 2D planning vs. 201.15 + or - 15.09 mm(3) in 3D planning). The volume of PTV which received 90% of the prescribed dose was 96.9 + or - 4.41 cm(3) in 2D planning and 97.2 + or - 2.61 cm(3) in 3D planning (p >0.05). 3D conformal radiotherapy (RT) for PNS tumors enables the delivery of radiation to the tumor with respect to critical organs with a lower toxicity to the optic pathway.

2D-3D MIGRATION AND CONFORMATIONAL MULTIPLICATION OF CHEMICALS IN LARGE CHEMICAL INVENTORIES

EPA Science Inventory

Chemical interactions are three-dimensional (3D) in nature and require modeling chemicals as 3D entities. In turn, using 3D models of chemicals leads to the realization that a single 2D structure can have hundreds of different conformations, and the electronic properties of these...

Three-dimensional structural dynamics and fluctuations of DNA-nanogold conjugates by individual-particle electron tomography

NASA Astrophysics Data System (ADS)

Zhang, Lei; Lei, Dongsheng; Smith, Jessica M.; Zhang, Meng; Tong, Huimin; Zhang, Xing; Lu, Zhuoyang; Liu, Jiankang; Alivisatos, A. Paul; Ren, Gang

2016-03-01

DNA base pairing has been used for many years to direct the arrangement of inorganic nanocrystals into small groupings and arrays with tailored optical and electrical properties. The control of DNA-mediated assembly depends crucially on a better understanding of three-dimensional structure of DNA-nanocrystal-hybridized building blocks. Existing techniques do not allow for structural determination of these flexible and heterogeneous samples. Here we report cryo-electron microscopy and negative-staining electron tomography approaches to image, and three-dimensionally reconstruct a single DNA-nanogold conjugate, an 84-bp double-stranded DNA with two 5-nm nanogold particles for potential substrates in plasmon-coupling experiments. By individual-particle electron tomography reconstruction, we obtain 14 density maps at ~2-nm resolution. Using these maps as constraints, we derive 14 conformations of dsDNA by molecular dynamics simulations. The conformational variation is consistent with that from liquid solution, suggesting that individual-particle electron tomography could be an expected approach to study DNA-assembling and flexible protein structure and dynamics.

Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT.

PubMed

Kumar, Gaurav; Rawat, Sheh; Puri, Abhishek; Sharma, Manoj Kumar; Chadha, Pranav; Babu, Anand Giri; Yadav, Girigesh

2012-01-01

Multimodality therapy for esophageal cancer can cause various kinds of treatment-related sequelae, especially pulmonary toxicities. This prospective study aims to investigate the clinical and dosimetric parameters predicting lung injury in patients undergoing radiation therapy for esophageal cancer. Forty-five esophageal cancer patients were prospectively analyzed. The pulmonary toxicities (or sequelae) were evaluated by comparing chest X-ray films, pulmonary function tests and symptoms caused by pulmonary damage before and after treatment. All patients were treated with either three-dimensional radiotherapy (3DCRT) or with intensity-modulated radiotherapy (IMRT). The planning dose volume histogram was used to compute the lung volumes receiving more than 5, 10, 20 and 30 Gy (V5, V10, V20, V30) and mean lung dose. V20 was larger in the IMRT group than in the 3DCRT group (p = 0.002). V20 (>15%) and V30 (>20%) resulted in a statistically significant increase in the occurrence of chronic pneumonitis (p = 0.03) and acute pneumonitis (p = 0.007), respectively. The study signifies that a larger volume of lung receives lower doses because of multiple beam arrangement and a smaller volume of lung receives higher doses because of better dose conformity in IMRT plans. Acute pneumonitis correlates more with V30 values, whereas chronic pneumonitis was predominantly seen in patients with higher V20 values.

Particle-tracking analysis of contributing areas of public-supply wells in simple and complex flow systems, Cape Cod, Massachusetts

USGS Publications Warehouse

Barlow, Paul M.

1997-01-01

Steady-state, two- and three-dimensional, ground-water-flow models coupled with particle tracking were evaluated to determine their effectiveness in delineating contributing areas of wells pumping from stratified-drift aquifers of Cape Cod, Massachusetts. Several contributing areas delineated by use of the three-dimensional models do not conform to simple ellipsoidal shapes that are typically delineated by use of two-dimensional analytical and numerical modeling techniques and included discontinuous areas of the water table.

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PubMed

Rosenzweig, K E; Mychalczak, B; Fuks, Z; Hanley, J; Burman, C; Ling, C C; Armstrong, J; Ginsberg, R; Kris, M G; Raben, A; Leibel, S

2000-01-01

Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

Holography for Schrödinger backgrounds

NASA Astrophysics Data System (ADS)

Guica, Monica; Skenderis, Kostas; Taylor, Marika; van Rees, Balt C.

2011-02-01

We discuss holography for Schrödinger solutions of both topologically massive gravity in three dimensions and massive vector theories in ( d + 1) dimensions. In both cases the dual field theory can be viewed as a d-dimensional conformal field theory (two dimensional in the case of TMG) deformed by certain operators that respect the Schrödinger symmetry. These operators are irrelevant from the viewpoint of the relativistic conformal group but they are exactly marginal with respect to the non-relativistic conformal group. The spectrum of linear fluctuations around the background solutions corresponds to operators that are labeled by their scaling dimension and the lightcone momentum k v . We set up the holographic dictionary and compute 2-point functions of these operators both holographically and in field theory using conformal perturbation theory and find agreement. The counterterms needed for holographic renormalization are non-local in the v lightcone direction.

Grid generation using classical techniques

NASA Technical Reports Server (NTRS)

Moretti, G.

1980-01-01

A brief historical review of conformal mapping and its applications to problems in fluid mechanics and electromagnetism is presented. The use of conformal mapping as a grid generator is described. The philosophy of the 'closed form' approach and its application to a Neumann problem is discussed. Karman-Trefftz mappings and grids for ablated, three dimensional bodies are also discussed.

The consequences of two distinct reaction coordinates in the decomposition of the ethylamine cation conformers

NASA Astrophysics Data System (ADS)

Petersen, Allan C.; Sølling, Theis I.

2018-06-01

The ethylamine cation CH3CH2NH2+ is shown to loose CH3 accompanied by a bimodal kinetic energy release. CH3CH2NH2+ exists in two conformeric forms, which are computationally shown to be distinct minima. The barrier separating the conformers is modest compared to the energy requirement for dissociation, and the conformers are so easily interconverted that the reactions take place from a mixture of the two conformers in equilibrium. However, once a reaction begins it is conformer-specific. The reaction from one conformational origin takes place by simple cleavage along a one-dimensional reaction coordinate, whereas reaction from the other origin is by a complex reaction mechanism with a two- or possibly three-dimensional reaction coordinate. Reaction by the former mechanism is a statistical process associated with a low kinetic energy release (KER), while the latter is non-statistical giving rise to a very low KER. The experimental result is a composite signal due to the superposition of two simple Gaussians, each corresponding to their respective KER.

Three-Dimensional Conformation of Folded Polymers in Single Crystals

NASA Astrophysics Data System (ADS)

Hong, You-lee; Yuan, Shichen; Li, Zhen; Ke, Yutian; Nozaki, Koji; Miyoshi, Toshikazu

2015-10-01

The chain-folding mechanism and structure of semicrystalline polymers have long been controversial. Solid-state NMR was applied to determine the chain trajectory of 13C CH3 -labeled isotactic poly(1-butene) (i PB 1 ) in form III chiral single crystals blended with nonlabeled i PB 1 crystallized in dilute solutions under low supercooling. An advanced 13C - 13C double-quantum NMR technique probing the spatial proximity pattern of labeled 13C nuclei revealed that the chains adopt a three-dimensional (3D) conformation in single crystals. The determined results indicate a two-step crystallization process of (i) cluster formation via self-folding in the precrystallization stage and (ii) deposition of the nanoclusters as a building block at the growth front in single crystals.

Recent advances in intensity modulated radiotherapy and proton therapy for esophageal cancer.

PubMed

Xi, Mian; Lin, Steven H

2017-07-01

Radiotherapy is an important component of the standard of care for esophageal cancer. In the past decades, significant improvements in the planning and delivery of radiation techniques have led to better dose conformity to the target volume and improved normal tissue sparing. Areas covered: This review focuses on the advances in radiotherapy techniques and summarizes the availably dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, proton therapy, and four-dimensional radiotherapy for esophageal cancer, and discusses the challenges and future development of proton therapy. Expert commentary: Although three-dimensional conformal radiotherapy is the standard radiotherapy technique in esophageal cancer, the retrospectively comparative studies strongly suggest that the dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can translate into improved clinical outcomes, despite the lack of prospective randomized evidence. As a novel form of conventional IMRT technique, volumetric modulated arc therapy can produce equivalent or superior dosimetric quality with significantly higher treatment efficiency in esophageal cancer. Compared with photon therapy, proton therapy has the potential to achieve further clinical improvement due to their physical properties; however, prospective clinical data, long-term results, and cost-effectiveness are needed.

Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT).

PubMed

Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

2013-12-01

Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147-53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose-volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques.

Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

PubMed Central

Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

2013-01-01

Introduction Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. Methods A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. Results The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. Conclusion The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques. PMID:26229623

Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

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

Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRTmore » plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques.« less

Mellin transforming the minimal model CFTs: AdS/CFT at strong curvature

DOE PAGES

Lowe, David A.

2016-07-14

Mack has conjectured that all conformal field theories are equivalent to string theories. Here, we explore the example of the two-dimensional minimal model CFTs and confirm that the Mellin transformed amplitudes have the desired properties of string theory in three-dimensional anti-de Sitter spacetime.

Self-dual Skyrmions on the spheres S2 N +1

NASA Astrophysics Data System (ADS)

Amari, Y.; Ferreira, L. A.

2018-04-01

We construct self-dual sectors for scalar field theories on a (2 N +2 )-dimensional Minkowski space-time with the target space being the 2 N +1 -dimensional sphere S2 N +1. The construction of such self-dual sectors is made possible by the introduction of an extra functional in the action that renders the static energy and the self-duality equations conformally invariant on the (2 N +1 )-dimensional spatial submanifold. The conformal and target-space symmetries are used to build an ansatz that leads to an infinite number of exact self-dual solutions with arbitrary values of the topological charge. The five-dimensional case is discussed in detail, where it is shown that two types of theories admit self-dual sectors. Our work generalizes the known results in the three-dimensional case that lead to an infinite set of self-dual Skyrmion solutions.

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

Three ways to solve critical ϕ4 theory on 4 ‑ 𝜖 dimensional real projective space: Perturbation, bootstrap, and Schwinger-Dyson equation

NASA Astrophysics Data System (ADS)

Hasegawa, Chika; Nakayama, Yu

2018-03-01

In this paper, we solve the two-point function of the lowest dimensional scalar operator in the critical ϕ4 theory on 4 ‑ 𝜖 dimensional real projective space in three different methods. The first is to use the conventional perturbation theory, and the second is to impose the cross-cap bootstrap equation, and the third is to solve the Schwinger-Dyson equation under the assumption of conformal invariance. We find that the three methods lead to mutually consistent results but each has its own advantage.

A three-dimensional Dirichlet-to-Neumann operator for water waves over topography

NASA Astrophysics Data System (ADS)

Andrade, D.; Nachbin, A.

2018-06-01

Surface water waves are considered propagating over highly variable non-smooth topographies. For this three dimensional problem a Dirichlet-to-Neumann (DtN) operator is constructed reducing the numerical modeling and evolution to the two dimensional free surface. The corresponding Fourier-type operator is defined through a matrix decomposition. The topographic component of the decomposition requires special care and a Galerkin method is provided accordingly. One dimensional numerical simulations, along the free surface, validate the DtN formulation in the presence of a large amplitude, rapidly varying topography. An alternative, conformal mapping based, method is used for benchmarking. A two dimensional simulation in the presence of a Luneburg lens (a particular submerged mound) illustrates the accurate performance of the three dimensional DtN operator.

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

NASA Astrophysics Data System (ADS)

Ono, Junichi; Takada, Shoji; Saito, Shinji

2015-06-01

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.

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

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

Ono, Junichi; Takada, Shoji; Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502

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 hierarchicalmore » 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.« less

Vibrational cross-angles in condensed molecules: a structural tool.

PubMed

Chen, Hailong; Zhang, Yufan; Li, Jiebo; Liu, Hongjun; Jiang, De-En; Zheng, Junrong

2013-09-05

The fluctuations of three-dimensional molecular conformations of a molecule in different environments play critical roles in many important chemical and biological processes. X-ray diffraction (XRD) techniques and nuclear magnetic resonance (NMR) methods are routinely applied to monitor the molecular conformations in condensed phases. However, some special requirements of the methods have prevented them from exploring many molecular phenomena at the current stage. Here, we introduce another method to resolve molecular conformations based on an ultrafast MIR/T-Hz multiple-dimensional vibrational spectroscopic technique. The model molecule (4'-methyl-2'-nitroacetanilide, MNA) is prepared in two of its crystalline forms and liquid samples. Two polarized ultrafast infrared pulses are then used to determine the cross-angles of vibrational transition moment directions by exciting one vibrational band and detecting the induced response on another vibrational band of the molecule. The vibrational cross-angles are then converted into molecular conformations with the aid of calculations. The molecular conformations determined by the method are supported by X-ray diffraction and molecular dynamics simulation results. The experimental results suggest that thermodynamic interactions with solvent molecules are not altering the molecular conformations of MNA in the solutions to control their ultimate conformations in the crystals.

3D printing of shape-conformable thermoelectric materials using all-inorganic Bi2Te3-based inks

NASA Astrophysics Data System (ADS)

Kim, Fredrick; Kwon, Beomjin; Eom, Youngho; Lee, Ji Eun; Park, Sangmin; Jo, Seungki; Park, Sung Hoon; Kim, Bong-Seo; Im, Hye Jin; Lee, Min Ho; Min, Tae Sik; Kim, Kyung Tae; Chae, Han Gi; King, William P.; Son, Jae Sung

2018-04-01

Thermoelectric energy conversion offers a unique solution for generating electricity from waste heat. However, despite recent improvements in the efficiency of thermoelectric materials, the widespread application of thermoelectric generators has been hampered by challenges in fabricating thermoelectric materials with appropriate dimensions to perfectly fit heat sources. Herein, we report an extrusion-based three-dimensional printing method to produce thermoelectric materials with geometries suitable for heat sources. All-inorganic viscoelastic inks were synthesized using Sb2Te3 chalcogenidometallate ions as inorganic binders for Bi2Te3-based particles. Three-dimensional printed materials with various geometries showed homogenous thermoelectric properties, and their dimensionless figure-of-merit values of 0.9 (p-type) and 0.6 (n-type) were comparable to the bulk values. Conformal cylindrical thermoelectric generators made of 3D-printed half rings mounted on an alumina pipe were studied both experimentally and computationally. Simulations show that the power output of the conformal, shape-optimized generator is higher than that of conventional planar generators.

Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma.

PubMed

Bradley, Jeffrey; Graham, Mary V; Winter, Kathryn; Purdy, James A; Komaki, Ritsuko; Roa, Wilson H; Ryu, Janice K; Bosch, Walter; Emami, Bahman

2005-02-01

To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer. A total of 179 patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation dose levels depending on the percentage of the total lung volume that received >20 Gy with the treatment plan (V(20)). Patients with a V(20) <25% (Group 1) received 70.9 Gy in 33 fractions, 77.4 Gy in 36 fractions, 83.8 Gy in 39 fractions, and 90.3 Gy in 42 fractions, successively. Patients with a V(20) of 25-36% (Group 2) received doses of 70.9 Gy and 77.4 Gy, successively. The treatment arm for patients with a V(20) > or =37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days after the start of radiotherapy were scored as late toxicities. The estimated toxicity rates were calculated on the basis of the cumulative incidence method. The following acute Grade 3 or worse toxicities were observed for Group 1: 70.9 Gy (1 case of weight loss), 77.4 Gy (nausea and hematologic toxicity in 1 case each), 83.8 Gy (1 case of hematologic toxicity), and 90.3 Gy (3 cases of lung toxicity). The following acute Grade 3 or worse toxicities were observed for Group 2: none at 70.9 Gy and 2 cases of lung toxicity at 77.4 Gy. No patients developed acute Grade 3 or worse esophageal toxicity. The estimated rate of Grade 3 or worse late lung toxicity at 18 months was 7%, 16%, 0%, and 13% for Group 1 patients receiving 70.9, 77.4, 83.8, or 90.3 Gy, respectively. Group 2 patients had an estimated late lung toxicity rate of 15% at 18 months for both 70.9 and 77.4 Gy. The prognostic factors for late pneumonitis in multivariate analysis were the mean lung dose and V(20). The estimated rate of late Grade 3 or worse esophageal toxicity at 18 months was 8%, 0%, 4%, and 6%, for Group 1 patients receiving 70.9, 77.4, 83.8, 90.3 Gy, respectively, and 0% and 5%, respectively, for Group 2 patients receiving 70.9 and 77.4 Gy. The dyspnea index scoring at baseline and after therapy for functional impairment, magnitude of task, and magnitude of effort revealed no change in 63%, functional pulmonary loss in 23%, and pulmonary improvement in 14% of patients. The observed locoregional control and overall survival rates were each similar among the study arms within each dose level of Groups 1 and 2. Locoregional control was achieved in 50-78% of patients. Thirty-one patients developed regional nodal failure. The location of nodal failure in relationship to the RT volume was documented in 28 of these 31 patients. Twelve patients had isolated elective nodal failures. Fourteen patients had regional failure in irradiated nodal volumes. Two patients had both elective nodal and irradiated nodal failure. The radiation dose was safely escalated using three-dimensional conformal techniques to 83.8 Gy for patients with V(20) values of <25% (Group 1) and to 77.4 Gy for patients with V(20) values between 25% and 36% (Group 2), using fraction sizes of 2.15 Gy. The 90.3-Gy dose level was too toxic, resulting in dose-related deaths in 2 patients. Elective nodal failure occurred in <10% of patients.

Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning

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

Tho, Lye Mun; Glegg, Martin; Paterson, Jennifer

2006-10-01

Purpose: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Methods and Materials: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervalsmore » (V{sub 5}, V{sub 1}, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. Results: VSB correlated strongly with diarrheal severity at every dose level (p < 0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p {<=} 0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p = 0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p = 0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V{sub 5} and V{sub 15}. Conclusions: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further investigation.« less

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern

PubMed Central

2013-01-01

Background To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Methods Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1–3 months after CCRT. Results With a median follow-up of 34 months (range, 2–116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). Conclusions 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors. PMID:24139225

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern.

PubMed

Bao, Yong; Liu, ShiLiang; Zhou, QiChao; Cai, PeiQiang; Anfossi, Simone; Li, QiaoQiao; Hu, YongHong; Liu, MengZhong; Fu, JianHua; Rong, TieHua; Li, Qun; Liu, Hui

2013-10-18

To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1-3 months after CCRT. With a median follow-up of 34 months (range, 2-116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors.

Phase II Study of Vinorelbine and Estramustine in Combination With Conformational Radiotherapy for Patients With High-Risk Prostate Cancer

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

Carles, Joan, E-mail: jocarles@vhebron.ne; Nogue, Miguel; Sole, Josep M.

Purpose: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. Methods and Materials: Fifty patients received estramustine, 600 mg/m{sup 2} daily, and vinorelbine, 25 mg/m{sup 2}, on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. Results: All patients were evaluated for response and toxicity. Progression-free survival at 5 yearsmore » was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. Conclusions: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.« less

Intensity-Modulated Radiotherapy Might Increase Pneumonitis Risk Relative to Three-Dimensional Conformal Radiotherapy in Patients Receiving Combined Chemotherapy and Radiotherapy: A Modeling Study of Dose Dumping

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

Vogelius, Ivan S.; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI; Department of Radiation Oncology, Rigshospitalet

2011-07-01

Purpose: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeledmore » as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.« less

Therapeutic effect of high-dose three-dimensional conformal radiotherapy and conventional radiotherapy for non-small-cell lung cancer.

PubMed

Xu, Su-Jun; Shi, Yu-Sheng; Song, Hai-Chun; Chen, Long-Hua

2002-10-01

To improve the therapeutic effect of radiotherapy without increasing the risk of radiation injury in patients with non-small cell lung cancer (NSCLC). From August 1998 to August 1999, 135 patients with NSCLC received radiotherapy, of whom 62 were treated with high-dose three-dimensional conformal radiotherapy (3D-CRT) at the total dose of 48 to 64 Gy in 6 to 8 fractions implemented in a course of 2 to 3 weeks, 6 to 8 Gy for each fraction. The other 73 patients underwent conventional radiotherapy (CR) at the total dose of 60 to 70 Gy in 30 to 35 fractions completed in 6 to 7 weeks. Follow-up study was conducted in all the cases, and CT-scan or magnetic resonance imaging was performed once every 3 months after the therapy to assess the local control rate, survival rate, radiation-induced lung and esophageal injuries. Three months after radiation therapy, complete remission of the lesions was achieved in 44.9% (CR group) and 77.8% (3D-CRT group) of the cases with the efficacy rates of 94.4% and 100% respectively, showing significant differences between the 2 groups (P<0.01). The 1- and 2-year survival rate of the patients in the 2 groups were 42.5% vs 77.8% and 30.1% vs 48.6% respectively, also with significant differences between the 2 groups (P<0.01). Significant difference also occurred in the 1- and 2-year local control rates between the 2 groups, but not in the incidences of radiation-induced lung and esophageal injuries. 3D-CRT may yield better therapeutic effect than CR does and has comparable safety with the latter.

Outcomes of Chemoradiotherapy With 5-Fluorouracil and Mitomycin C for Anal Cancer in Immunocompetent Versus Immunodeficient Patients

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

Seo, Yuji; Kinsella, Michael T.; Reynolds, Harry L.

2009-09-01

Purpose: Information is limited as to how we should treat invasive anal squamous cell carcinoma (SCC) in patients with chronic immunosuppression, since the majority of clinical studies to date have excluded such patients. The objective of this study is to compare treatment outcomes in immunocompetent (IC) versus immunodeficient (ID) patients with invasive anal SCC treated similarly with combined modality therapy. Methods and Materials: Between January 1999 and March 2007, a total of 36 consecutive IC and ID patients received concurrent chemoradiotherapy using three-dimensional conformal radiotherapy with infusional 5-fluorouracil and mitomycin C. The IC and ID groups consisted of 19 andmore » 17 patients, respectively, with 14 human immunodeficiency virus-positive (HIV+) and 3 post-solid organ transplant ID patients. There were no significant differences in tumor size, T stage, N stage, chemotherapy doses, or radiation doses between the two groups. Results: With a median follow-up of 3.1 years, no differences were found in overall survival, disease-specific survival, and colostomy-free survival. Three-year overall survival was 83.6% (95% CI = 68.2-100) and 91.7% (95% CI = 77.3-100) in the IC and ID groups, respectively. In addition, there were no differences in acute and late toxicity profiles between the two groups. In the human immunodeficiency virus-positive patients, Cox modeling showed no difference in overall survival by pretreatment CD4 counts (hazard ratio = 0.994, 95% CI = 0.98-1.01). No correlation was found between CD4 counts and the degree of acute toxicities. Conclusion: Our data suggest that standard combined modality therapy with three-dimensional conformal radiotherapy and 5-fluorouracil plus mitomycin C is as safe and effective for ID patients as for IC patients.« less

Predicting Three-Dimensional Conformations of Peptides Constructed of Only Glycine, Alanine, Aspartic Acid, and Valine

NASA Astrophysics Data System (ADS)

Oda, Akifumi; Fukuyoshi, Shuichi

2015-06-01

The GADV hypothesis is a form of the protein world hypothesis, which suggests that life originated from proteins (Lacey et al. 1999; Ikehara 2002; Andras 2006). In the GADV hypothesis, life is thought to have originated from primitive proteins constructed of only glycine, alanine, aspartic acid, and valine ([GADV]-proteins). In this study, the three-dimensional (3D) conformations of randomly generated short [GADV]-peptides were computationally investigated using replica-exchange molecular dynamics (REMD) simulations (Sugita and Okamoto 1999). Because the peptides used in this study consisted of only 20 residues each, they could not form certain 3D structures. However, the conformational tendencies of the peptides were elucidated by analyzing the conformational ensembles generated by REMD simulations. The results indicate that secondary structures can be formed in several randomly generated [GADV]-peptides. A long helical structure was found in one of the hydrophobic peptides, supporting the conjecture of the GADV hypothesis that many peptides aggregated to form peptide multimers with enzymatic activity in the primordial soup. In addition, these results indicate that REMD simulations can be used for the structural investigation of short peptides.

Three-dimensional structural dynamics and fluctuations of DNA-nanogold conjugates by individual-particle electron tomography

DOE PAGES

Zhang, Lei; Lei, Dongsheng; Smith, Jessica M.; ...

2016-03-30

DNA base pairing has been used for many years to direct the arrangement of inorganic nanocrystals into small groupings and arrays with tailored optical and electrical properties. The control of DNA-mediated assembly depends crucially on a better understanding of three-dimensional structure of DNA-nanocrystal-hybridized building blocks. Existing techniques do not allow for structural determination of these flexible and heterogeneous samples. Here we report cryo-electron microscopy and negative-staining electron tomography approaches to image, and three-dimensionally reconstruct a single DNA-nanogold conjugate, an 84-bp double-stranded DNA with two 5-nm nanogold particles for potential substrates in plasmon-coupling experiments. By individual-particle electron tomography reconstruction, we obtainmore » 14 density maps at ~ 2-nm resolution . Using these maps as constraints, we derive 14 conformations of dsDNA by molecular dynamics simulations. The conformational variation is consistent with that from liquid solution, suggesting that individual-particle electron tomography could be an expected approach to study DNA-assembling and flexible protein structure and dynamics.« less

Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation

PubMed Central

2012-01-01

Background To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC) patients with a dose of 60 Gy/30f. Methods Thirty-nine patients with medically inoperable T1–4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT) with involved-field radiation (IFI). The conformal clinical target volume (CTV) was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV) and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED) guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD) and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Results Under a 60 Gy dosage, the median Dmean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Conclusions Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions. PMID:23186308

Three-dimensional conformal radiotherapy by delineations on CT-based simulation in different respiratory phases for the treatment of senile patients with non-small cell lung cancer.

PubMed

Wang, Weifeng; Yuan, Feng; Wang, Guoping; Lin, Zhiren; Pan, Yanling; Chen, Longhua

2015-01-01

This study aimed to evaluate the application of three-dimensional conformal radiotherapy (3D-CRT) for elderly patients with non-small cell lung cancer (NSCLC) based on computed tomography (CT) simulations in different respiratory phases. A total of 64 patients aged >70 years old with NSCLC were treated by 3D-CRT using CT images in different respiratory phases. The gross tumor volumes (GTVs) at the end of inspiration and end of expiration were combined to obtain the total GTV, which was close to the motional range of tumors during respiration, and no additional expansion of the clinical target volume (CTAV) to planning target volume (PTV) (CTAV:PTV) was included during the recording of respiratory movements. Patients were also planned according to the classic 3D-CRT approach. Efficacy, prognostic factors, and side effects were evaluated. Compared with the classic approach, the average PTV was 18.9% lower (median: 17.3%), and the average lung volume receiving a prescribed dose for a tumor was 22.4% lower (median: 20.9%). The 1-, 2-, and 3-year survival rates were 70.6%, 54.9%, and 29.4%, respectively, with an overall tumor response rate of 79.7%. The Karnofsky performance status and N stage were independent prognostic factors, whereas age was not. Without affecting therapeutic effects, CT simulations in different respiratory phases were well-tolerated in elderly patients with NSCLC, could effectively reduce PTV, and could improve the quality of life.

Ray-tracing in three dimensions for calculation of radiation-dose calculations. Master's thesis

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

Kennedy, D.R.

1986-05-27

This thesis addresses several methods of calculating the radiation-dose distribution for use by technicians or clinicians in radiation-therapy treatment planning. It specifically covers the calculation of the effective pathlength of the radiation beam for use in beam models representing the dose distribution. A two-dimensional method by Bentley and Milan is compared to the method of Strip Trees developed by Duda and Hart and then a three-dimensional algorithm built to perform the calculations in three dimensions. The use of PRISMS conforms easily to the obtained CT Scans and provides a means of only doing two-dimensional ray-tracing while performing three-dimensional dose calculations.more » This method is already being applied and used in actual calculations.« less

Higher spin conformal geometry in three dimensions and prepotentials for higher spin gauge fields

NASA Astrophysics Data System (ADS)

Henneaux, Marc; Hörtner, Sergio; Leonard, Amaury

2016-01-01

We study systematically the conformal geometry of higher spin bosonic gauge fields in three spacetime dimensions. We recall the definition of the Cotton tensor for higher spins and establish a number of its properties that turn out to be key in solving in terms of prepotentials the constraint equations of the Hamiltonian (3 + 1) formulation of four-dimensional higher spin gauge fields. The prepotentials are shown to exhibit higher spin conformal symmetry. Just as for spins 1 and 2, they provide a remarkably simple, manifestly duality invariant formulation of the theory. While the higher spin conformal geometry is developed for arbitrary bosonic spin, we explicitly perform the Hamiltonian analysis and derive the solution of the constraints only in the illustrative case of spin 3. In a separate publication, the Hamiltonian analysis in terms of prepotentials is extended to all bosonic higher spins using the conformal tools of this paper, and the same emergence of higher spin conformal symmetry is confirmed.

Multivariate analysis of survival, local control, and time to distant metastases in patients with unresectable non-small-cell lung carcinoma treated with 3-dimensional conformal radiation therapy with or without concurrent chemotherapy.

PubMed

Wolski, Michal J; Bhatnagar, Ajay; Flickinger, John C; Belani, Chandra P; Ramalingam, Suresh; Greenberger, Joel S

2005-09-01

Three-dimensional (3D) conformal radiation therapy (CRT) and chemotherapy have recently improved lung cancer management. We reviewed outcomes in 68 patients with unresectable stage I-III non-small-cell lung cancer. Treatment consisted of 3D CRT alone or with concurrent chemotherapy (CCR). Concurrent chemotherapy improved survival, to a median of 17 months +/- 4.9 months, compared with 8 months+/- 4.1 months for the radiation therapy (RT) alone group (P=0.0347). The 2- and 5-year survival rates were 40.3%+/-7.7% and 14.1%+/-6.4%, respectively, with CCR, compared with 19.6%+/- 9.6% and 0, respectively, for RT alone. In a subgroup analysis for age > 65, patients who received CCR (n=20) had significantly improved survival and local control (P=0.005 and P=0.0286, respectively). Acute esophageal toxicity Radiation Therapy Oncology Group grade >or= 3 was significantly higher in the CCR group and correlated with the RT dose (19% in CCR vs. 0 in RT, P=0.0234; P=0.050). The overall incidences of esophageal and pulmonary toxicity grade >or= 3 were 20.6% and 5.9%, respectively. Our study confirms that CCR is associated with improved survival over RT alone, with a tolerable increase in acute toxicity.

Chern-Simons theory on a hypersphere

NASA Astrophysics Data System (ADS)

McKeon, D. G. C.

1990-08-01

We demonstrate that a non-Abelian Chern-Simons field theory can be mapped from three-dimensional Euclidean space onto the surface of a sphere in four dimensions using a stereographic projection. The theory is manifestly invariant under a rotation on the four-dimensional hypersphere. An explicit one-loop calculation shows that the curvature of the hypersphere induces a conformal anomaly.

Directly Reconstructing Principal Components of Heterogeneous Particles from Cryo-EM Images

PubMed Central

Tagare, Hemant D.; Kucukelbir, Alp; Sigworth, Fred J.; Wang, Hongwei; Rao, Murali

2015-01-01

Structural heterogeneity of particles can be investigated by their three-dimensional principal components. This paper addresses the question of whether, and with what algorithm, the three-dimensional principal components can be directly recovered from cryo-EM images. The first part of the paper extends the Fourier slice theorem to covariance functions showing that the three-dimensional covariance, and hence the principal components, of a heterogeneous particle can indeed be recovered from two-dimensional cryo-EM images. The second part of the paper proposes a practical algorithm for reconstructing the principal components directly from cryo-EM images without the intermediate step of calculating covariances. This algorithm is based on maximizing the (posterior) likelihood using the Expectation-Maximization algorithm. The last part of the paper applies this algorithm to simulated data and to two real cryo-EM data sets: a data set of the 70S ribosome with and without Elongation Factor-G (EF-G), and a data set of the inluenza virus RNA dependent RNA Polymerase (RdRP). The first principal component of the 70S ribosome data set reveals the expected conformational changes of the ribosome as the EF-G binds and unbinds. The first principal component of the RdRP data set reveals a conformational change in the two dimers of the RdRP. PMID:26049077

Conformational landscape of a virus by single-particle X-ray scattering

DOE PAGES

Hosseinizadeh, Ahmad; Mashayekhi, Ghoncheh; Copperman, Jeremy; ...

2017-08-14

Using a manifold-based analysis of experimental diffraction snapshots from an X-ray free electron laser, we determine the three-dimensional structure and conformational landscape of the PR772 virus to a detector-limited resolution of 9 nm. Our results indicate that a single conformational coordinate controls reorganization of the genome, growth of a tubular structure from a portal vertex and release of the genome. Furthermore, these results demonstrate that single-particle X-ray scattering has the potential to shed light on key biological processes.

Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder.

PubMed

Li, Qiu-yang; Tang, Jie; He, En-hui; Li, Yan-mi; Zhou, Yun; Zhang, Xu; Chen, Guangfu

2012-11-01

The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements were 0.717, 0.794 and 0.914. Three-dimensional contrast-enhanced ultrasound imaging, with contrast-enhanced spatial visualization is clinical useful for differentiating invasive and noninvasive neoplasms of urinary bladder objectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Structural diversity of supercoiled DNA

PubMed Central

Irobalieva, Rossitza N.; Fogg, Jonathan M.; Catanese, Daniel J.; Sutthibutpong, Thana; Chen, Muyuan; Barker, Anna K.; Ludtke, Steven J.; Harris, Sarah A.; Schmid, Michael F.; Chiu, Wah; Zechiedrich, Lynn

2015-01-01

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function. PMID:26455586

Structural diversity of supercoiled DNA

NASA Astrophysics Data System (ADS)

Irobalieva, Rossitza N.; Fogg, Jonathan M.; Catanese, Daniel J.; Sutthibutpong, Thana; Chen, Muyuan; Barker, Anna K.; Ludtke, Steven J.; Harris, Sarah A.; Schmid, Michael F.; Chiu, Wah; Zechiedrich, Lynn

2015-10-01

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

Method to planarize three-dimensional structures to enable conformal electrodes

DOEpatents

Nikolic, Rebecca J; Conway, Adam M; Graff, Robert T; Reinhardt, Catherine; Voss, Lars F; Shao, Qinghui

2012-11-20

Methods for fabricating three-dimensional PIN structures having conformal electrodes are provided, as well as the structures themselves. The structures include a first layer and an array of pillars with cavity regions between the pillars. A first end of each pillar is in contact with the first layer. A segment is formed on the second end of each pillar. The cavity regions are filled with a fill material, which may be a functional material such as a neutron sensitive material. The fill material covers each segment. A portion of the fill material is etched back to produce an exposed portion of the segment. A first electrode is deposited onto the fill material and each exposed segment, thereby forming a conductive layer that provides a common contact to each the exposed segment. A second electrode is deposited onto the first layer.

Adventures in Topological Field Theory

NASA Astrophysics Data System (ADS)

Horne, James H.

1990-01-01

This thesis consists of 5 parts. In part I, the topological Yang-Mills theory and the topological sigma model are presented in a superspace formulation. This greatly simplifies the field content of the theories, and makes the Q-invariance more obvious. The Feynman rules for the topological Yang -Mills theory are derived. We calculate the one-loop beta-functions of the topological sigma model in superspace. The lattice version of these theories is presented. The self-duality constraints of both models lead to spectrum doubling. In part II, we show that conformally invariant gravity in three dimensions is equivalent to the Yang-Mills gauge theory of the conformal group in three dimensions, with a Chern-Simons action. This means that conformal gravity is finite and exactly soluble. In part III, we derive the skein relations for the fundamental representations of SO(N), Sp(2n), Su(m| n), and OSp(m| 2n). These relations can be used recursively to calculate the expectation values of Wilson lines in three-dimensional Chern-Simons gauge theory with these gauge groups. A combination of braiding and tying of Wilson lines completely describes the skein relations. In part IV, we show that the k = 1 two dimensional gravity amplitudes at genus 3 agree precisely with the results from intersection theory on moduli space. Predictions for the genus 4 intersection numbers follow from the two dimensional gravity theory. In part V, we discuss the partition function in two dimensional gravity. For the one matrix model at genus 2, we use the partition function to derive a recursion relation. We show that the k = 1 amplitudes completely determine the partition function at arbitrary genus. We present a conjecture for the partition function for the arbitrary topological field theory coupled to topological gravity.

Controllable load sharing for soft adhesive interfaces on three-dimensional surfaces.

PubMed

Song, Sukho; Drotlef, Dirk-Michael; Majidi, Carmel; Sitti, Metin

2017-05-30

For adhering to three-dimensional (3D) surfaces or objects, current adhesion systems are limited by a fundamental trade-off between 3D surface conformability and high adhesion strength. This limitation arises from the need for a soft, mechanically compliant interface, which enables conformability to nonflat and irregularly shaped surfaces but significantly reduces the interfacial fracture strength. In this work, we overcome this trade-off with an adhesion-based soft-gripping system that exhibits enhanced fracture strength without sacrificing conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric microfibrillar adhesive membrane supported by a pressure-controlled deformable gripper body, the proposed soft-gripping system controls the bonding strength by changing its internal pressure and exploiting the mechanics of interfacial equal load sharing. The soft adhesion system can use up to ∼26% of the maximum adhesion of the fibrillar membrane, which is 14× higher than the adhering membrane without load sharing. Our proposed load-sharing method suggests a paradigm for soft adhesion-based gripping and transfer-printing systems that achieves area scaling similar to that of a natural gecko footpad.

Controllable load sharing for soft adhesive interfaces on three-dimensional surfaces

NASA Astrophysics Data System (ADS)

Song, Sukho; Drotlef, Dirk-Michael; Majidi, Carmel; Sitti, Metin

2017-05-01

For adhering to three-dimensional (3D) surfaces or objects, current adhesion systems are limited by a fundamental trade-off between 3D surface conformability and high adhesion strength. This limitation arises from the need for a soft, mechanically compliant interface, which enables conformability to nonflat and irregularly shaped surfaces but significantly reduces the interfacial fracture strength. In this work, we overcome this trade-off with an adhesion-based soft-gripping system that exhibits enhanced fracture strength without sacrificing conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric microfibrillar adhesive membrane supported by a pressure-controlled deformable gripper body, the proposed soft-gripping system controls the bonding strength by changing its internal pressure and exploiting the mechanics of interfacial equal load sharing. The soft adhesion system can use up to ˜26% of the maximum adhesion of the fibrillar membrane, which is 14× higher than the adhering membrane without load sharing. Our proposed load-sharing method suggests a paradigm for soft adhesion-based gripping and transfer-printing systems that achieves area scaling similar to that of a natural gecko footpad.

Controllable load sharing for soft adhesive interfaces on three-dimensional surfaces

PubMed Central

Song, Sukho; Drotlef, Dirk-Michael; Majidi, Carmel; Sitti, Metin

2017-01-01

For adhering to three-dimensional (3D) surfaces or objects, current adhesion systems are limited by a fundamental trade-off between 3D surface conformability and high adhesion strength. This limitation arises from the need for a soft, mechanically compliant interface, which enables conformability to nonflat and irregularly shaped surfaces but significantly reduces the interfacial fracture strength. In this work, we overcome this trade-off with an adhesion-based soft-gripping system that exhibits enhanced fracture strength without sacrificing conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric microfibrillar adhesive membrane supported by a pressure-controlled deformable gripper body, the proposed soft-gripping system controls the bonding strength by changing its internal pressure and exploiting the mechanics of interfacial equal load sharing. The soft adhesion system can use up to ∼26% of the maximum adhesion of the fibrillar membrane, which is 14× higher than the adhering membrane without load sharing. Our proposed load-sharing method suggests a paradigm for soft adhesion-based gripping and transfer-printing systems that achieves area scaling similar to that of a natural gecko footpad. PMID:28507143

Supersymmetric Yang-Mills theory on conformal supergravity backgrounds in ten dimensions

NASA Astrophysics Data System (ADS)

de Medeiros, Paul; Figueroa-O'Farrill, José

2016-03-01

We consider bosonic supersymmetric backgrounds of ten-dimensional conformal supergravity. Up to local conformal isometry, we classify the maximally supersymmetric backgrounds, determine their conformal symmetry superalgebras and show how they arise as near-horizon geometries of certain half-BPS backgrounds or as a plane-wave limit thereof. We then show how to define Yang-Mills theory with rigid supersymmetry on any supersymmetric conformal supergravity background and, in particular, on the maximally supersymmetric backgrounds. We conclude by commenting on a striking resemblance between the supersymmetric backgrounds of ten-dimensional conformal supergravity and those of eleven-dimensional Poincaré supergravity.

The Role of High-Dimensional Diffusive Search, Stabilization, and Frustration in Protein Folding

PubMed Central

Rimratchada, Supreecha; McLeish, Tom C.B.; Radford, Sheena E.; Paci, Emanuele

2014-01-01

Proteins are polymeric molecules with many degrees of conformational freedom whose internal energetic interactions are typically screened to small distances. Therefore, in the high-dimensional conformation space of a protein, the energy landscape is locally relatively flat, in contrast to low-dimensional representations, where, because of the induced entropic contribution to the full free energy, it appears funnel-like. Proteins explore the conformation space by searching these flat subspaces to find a narrow energetic alley that we call a hypergutter and then explore the next, lower-dimensional, subspace. Such a framework provides an effective representation of the energy landscape and folding kinetics that does justice to the essential characteristic of high-dimensionality of the search-space. It also illuminates the important role of nonnative interactions in defining folding pathways. This principle is here illustrated using a coarse-grained model of a family of three-helix bundle proteins whose conformations, once secondary structure has formed, can be defined by six rotational degrees of freedom. Two folding mechanisms are possible, one of which involves an intermediate. The stabilization of intermediate subspaces (or states in low-dimensional projection) in protein folding can either speed up or slow down the folding rate depending on the amount of native and nonnative contacts made in those subspaces. The folding rate increases due to reduced-dimension pathways arising from the mere presence of intermediate states, but decreases if the contacts in the intermediate are very stable and introduce sizeable topological or energetic frustration that needs to be overcome. Remarkably, the hypergutter framework, although depending on just a few physically meaningful parameters, can reproduce all the types of experimentally observed curvature in chevron plots for realizations of this fold. PMID:24739172

FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation properties

NASA Astrophysics Data System (ADS)

De Deene, Y.; Skyt, P. S.; Hil, R.; Booth, J. T.

2015-02-01

Three dimensional radiation dosimetry has received growing interest with the implementation of highly conformal radiotherapy treatments. The radiotherapy community faces new challenges with the commissioning of image guided and image gated radiotherapy treatments (IGRT) and deformable image registration software. A new three dimensional anthropomorphically shaped flexible dosimeter, further called ‘FlexyDos3D’, has been constructed and a new fast optical scanning method has been implemented that enables scanning of irregular shaped dosimeters. The FlexyDos3D phantom can be actuated and deformed during the actual treatment. FlexyDos3D offers the additional advantage that it is easy to fabricate, is non-toxic and can be molded in an arbitrary shape with high geometrical precision. The dosimeter formulation has been optimized in terms of dose sensitivity. The influence of the casting material and oxygen concentration has also been investigated. The radiophysical properties of this new dosimeter are discussed including stability, spatial integrity, temperature dependence of the dosimeter during radiation, readout and storage, dose rate dependence and tissue equivalence. The first authors Y De Deene and P S Skyt made an equivalent contribution to the experimental work presented in this paper.

Anaplastic thyroid cancer: Clinical outcomes with conformal radiotherapy.

PubMed

Bhatia, Aarti; Rao, Archana; Ang, Kie-Kian; Garden, Adam S; Morrison, William H; Rosenthal, David I; Evans, Douglas B; Clayman, Gary; Sherman, Steven I; Schwartz, David L

2010-07-01

The aim of this study was to review institutional outcomes for anaplastic thyroid cancer treated with conformal 3-dimensional radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT). In all, 53 consecutive patients were analyzed. Thirty-one (58%) patients were irradiated with curative intent. Median radiation dose was 55 Gray (Gy; range, 4-70 Gy). Thirteen (25%) patients received IMRT to a median 60 Gy (range, 39.9-69.0 Gy). Thirty-nine (74%) patients received chemotherapy with radiation. The Kaplan-Meier estimate of overall survival (OS) at 1 year for definitively irradiated patients was 29%. Patients without distant metastases receiving >or=50 Gy had superior survival outcomes; 5 such patients had no evidence of disease at last follow-up. Use of IMRT versus 3DRT did not influence toxicity. Outcomes for anaplastic thyroid cancer treated with 3DRT or IMRT remain equivalent to historical results. Healthy patients with localized disease who tolerate full dose irradiation can potentially enjoy prolonged survival. Biologically targeted radiosensitization merits prioritized investigation. (c) 2009 Wiley Periodicals, Inc.

Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity.

PubMed

Haefner, Matthias Felix; Lang, Kristin; Verma, Vivek; Koerber, Stefan Alexander; Uhlmann, Lorenz; Debus, Juergen; Sterzing, Florian

2017-08-15

Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts. We retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients. Mean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 - 0.916, p = 0.004). Factors clearly affecting survival were not observed. When comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.

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

Kole, Thomas P.; Aghayere, Osarhieme; Kwah, Jason

Purpose: To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Methods and Materials: Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters weremore » statistically evaluated using the Wilcoxon rank-sum test. Results: Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Conclusions: Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications.« less

Exploration of the relationship between topology and designability of conformations

NASA Astrophysics Data System (ADS)

Leelananda, Sumudu P.; Towfic, Fadi; Jernigan, Robert L.; Kloczkowski, Andrzej

2011-06-01

Protein structures are evolutionarily more conserved than sequences, and sequences with very low sequence identity frequently share the same fold. This leads to the concept of protein designability. Some folds are more designable and lots of sequences can assume that fold. Elucidating the relationship between protein sequence and the three-dimensional (3D) structure that the sequence folds into is an important problem in computational structural biology. Lattice models have been utilized in numerous studies to model protein folds and predict the designability of certain folds. In this study, all possible compact conformations within a set of two-dimensional and 3D lattice spaces are explored. Complementary interaction graphs are then generated for each conformation and are described using a set of graph features. The full HP sequence space for each lattice model is generated and contact energies are calculated by threading each sequence onto all the possible conformations. Unique conformation giving minimum energy is identified for each sequence and the number of sequences folding to each conformation (designability) is obtained. Machine learning algorithms are used to predict the designability of each conformation. We find that the highly designable structures can be distinguished from other non-designable conformations based on certain graphical geometric features of the interactions. This finding confirms the fact that the topology of a conformation is an important determinant of the extent of its designability and suggests that the interactions themselves are important for determining the designability.

Manufacturing method of photonic crystal

DOEpatents

Park, In Sung; Lee, Tae Ho; Ahn, Jin Ho; Biswas, Rana; Constant, Kristen P.; Ho, Kai-Ming; Lee, Jae-Hwang

2013-01-29

A manufacturing method of a photonic crystal is provided. In the method, a high-refractive-index material is conformally deposited on an exposed portion of a periodic template composed of a low-refractive-index material by an atomic layer deposition process so that a difference in refractive indices or dielectric constants between the template and adjacent air becomes greater, which makes it possible to form a three-dimensional photonic crystal having a superior photonic bandgap. Herein, the three-dimensional structure may be prepared by a layer-by-layer method.

Three-dimensional reconstruction of single-cell chromosome structure using recurrence plots.

PubMed

Hirata, Yoshito; Oda, Arisa; Ohta, Kunihiro; Aihara, Kazuyuki

2016-10-11

Single-cell analysis of the three-dimensional (3D) chromosome structure can reveal cell-to-cell variability in genome activities. Here, we propose to apply recurrence plots, a mathematical method of nonlinear time series analysis, to reconstruct the 3D chromosome structure of a single cell based on information of chromosomal contacts from genome-wide chromosome conformation capture (Hi-C) data. This recurrence plot-based reconstruction (RPR) method enables rapid reconstruction of a unique structure in single cells, even from incomplete Hi-C information.

Three-dimensional reconstruction of single-cell chromosome structure using recurrence plots

NASA Astrophysics Data System (ADS)

Hirata, Yoshito; Oda, Arisa; Ohta, Kunihiro; Aihara, Kazuyuki

2016-10-01

Single-cell analysis of the three-dimensional (3D) chromosome structure can reveal cell-to-cell variability in genome activities. Here, we propose to apply recurrence plots, a mathematical method of nonlinear time series analysis, to reconstruct the 3D chromosome structure of a single cell based on information of chromosomal contacts from genome-wide chromosome conformation capture (Hi-C) data. This recurrence plot-based reconstruction (RPR) method enables rapid reconstruction of a unique structure in single cells, even from incomplete Hi-C information.

Proteopedia: A Collaborative, Virtual 3D Web-Resource for Protein and Biomolecule Structure and Function

ERIC Educational Resources Information Center

Hodis, Eran; Prilusky, Jaime, Sussman, Joel L.

2010-01-01

Protein structures are hard to represent on paper. They are large, complex, and three-dimensional (3D)--four-dimensional if conformational changes count! Unlike most of their substrates, which can easily be drawn out in full chemical formula, drawing every atom in a protein would usually be a mess. Simplifications like showing only the surface of…

Superintegrable three-body systems on the line

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

Chanu, Claudia; Degiovanni, Luca; Rastelli, Giovanni

2008-11-15

We consider classical three-body interactions on a Euclidean line depending on the reciprocal distance of the particles and admitting four functionally independent quadratic in the momentum first integrals. These systems are multiseparable, superintegrable, and equivalent (up to rescalings) to a one-particle system in the three-dimensional Euclidean space. Common features of the dynamics are discussed. We show how to determine quantum symmetry operators associated with the first integrals considered here but do not analyze the corresponding quantum dynamics. The conformal multiseparability is discussed and examples of conformal first integrals are given. The systems considered here in generality include the Calogero, Wolfes,more » and other three-body interactions widely studied in mathematical physics.« less

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

Öğretici, Akın, E-mail: akinogretici@gmail.com; Akbaş, Uğur; Köksal, Canan

The aim of this research was to investigate the fetal doses of pregnant patients undergoing conformal radiotherapy or intensity-modulated radiation therapy (IMRT) for breast cancers. An Alderson Rando phantom was chosen to simulate a pregnant patient with breast cancer who is receiving radiation therapy. This phantom was irradiated using the Varian Clinac DBX 600 system (Varian Medical System, Palo Alto, CA) linear accelerator, according to the standard treatment plans of both three-dimensional conformal radiation therapy (3-D CRT) and IMRT techniques. Thermoluminescent dosimeters were used to measure the irradiated phantom's virtually designated uterus area. Thermoluminescent dosimeter measurements (in the phantom) revealedmore » that the mean cumulative fetal dose for 3-D CRT is 1.39 cGy and for IMRT it is 8.48 cGy, for a pregnant breast cancer woman who received radiation treatment of 50 Gy. The fetal dose was confirmed to increase by 70% for 3-D CRT and 40% for IMRT, if it is closer to the irradiated field by 5 cm. The mean fetal dose from 3-D CRT is 1.39 cGy and IMRT is 8.48 cGy, consistent with theoretic calculations. The IMRT technique causes the fetal dose to be 5 times more than that of 3-D CRT. Theoretic knowledge concerning the increase in the peripheral doses as the measurements approached the beam was also practically proven.« less

Dose-volumetric parameters of acute esophageal toxicity in patients with lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Kim, Tae Hyun; Cho, Kwan Ho; Pyo, Hong Ryull; Lee, Jin Soo; Han, Ji Youn; Zo, Jae Ill; Lee, Jong Mog; Hong, Eun Kyoung; Choi, Il Ju; Park, Sung Yong; Shin, Kyung Hwan; Kim, Dae Yong; Kim, Joo Young

2005-07-15

To retrospectively evaluate which dose-volumetric parameters are associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in lung cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). One hundred twenty-four lung cancer patients treated curatively with 3D-CRT were retrospectively analyzed. All patients received conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range, 54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients underwent curative surgery before RT. Ninety-two patients received chemotherapy (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was scored by Radiation Therapy Oncology Group criteria. The parameters analyzed included sex; age; Karnofsky performance score; weight loss; surgery; concurrent chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58 Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute length of the esophagus irradiated; the maximum and mean dose to the esophagus; and normal tissue complication probability. Of the 124 patients, 15 patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was no fatal Grade 5 AET. In univariate and multivariate logistic regression analyses, concurrent chemotherapy and V60 were significantly associated with the development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in 15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50 patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87 patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 > 30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy, severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of 7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037). Concurrent chemotherapy and V60 were associated with the development of severe AET > or = Grade 3. For patients being treated with concurrent chemotherapy, V60 is considered to be a useful parameter predicting the risk of severe AET after conventionally fractionated 3D-CRT for lung cancer.

Optimum aerodynamic design via boundary control

NASA Technical Reports Server (NTRS)

Jameson, Antony

1994-01-01

These lectures describe the implementation of optimization techniques based on control theory for airfoil and wing design. In previous studies it was shown that control theory could be used to devise an effective optimization procedure for two-dimensional profiles in which the shape is determined by a conformal transformation from a unit circle, and the control is the mapping function. Recently the method has been implemented in an alternative formulation which does not depend on conformal mapping, so that it can more easily be extended to treat general configurations. The method has also been extended to treat the Euler equations, and results are presented for both two and three dimensional cases, including the optimization of a swept wing.

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

PubMed

Keyerleber, M A; Gieger, T L; Erb, H N; Thompson, M S; McEntee, M C

2012-12-01

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures. © 2011 Blackwell Publishing Ltd.

Two-dimensional Kinetics Regulation of αLβ2-ICAM-1 Interaction by Conformational Changes of the αL-Inserted Domain*

PubMed Central

Zhang, Fang; Marcus, Warren D.; Goyal, Nimita H.; Selvaraj, Periasamy; Springer, Timothy A.; Zhu, Cheng

2006-01-01

The leukocyte integrin αLβ2 mediates cell adhesion and migration during inflammatory and immune responses. Ligand binding of αLβ2 is regulated by or induces conformational changes in the inserted (I) domain. By using a micropipette, we measured the conformational regulation of two-dimensional (2D) binding affinity and the kinetics of cell-bound intercellular adhesion molecule-1 interacting with αLβ2 or isolated I domain expressed on K562 cells. Locking the I domain into open and intermediate conformations with a disulfide bond increased the affinities by ~8000- and ~30-fold, respectively, from the locked closed conformation, which has similar affinity as the wild-type I domain. Most surprisingly, the 2D affinity increases were due mostly to the 2D on-rate increases, as the 2D off-rates only decreased by severalfold. The wild-type αLβ2, but not its I domain in isolation, could be up-regulated by Mn2+ or Mg2+ to have high affinities and on-rates. Locking the I domain in any of the three conformations abolished the ability of divalent cations to regulate 2D affinity. These results indicate that a downward displacement of the I domain C-terminal helix, induced by conformational changes of other domains of the αLβ2, is required for affinity and on-rate up-regulation. PMID:16234238

Combination of Transarterial Chemoembolization and Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus

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

Koo, Ja Eun; Kim, Jong Hoon; Lim, Young-Suk, E-mail: limys@amc.seoul.k

Purpose: To evaluate the effects of transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (CRT) in patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT). Methods and Materials: A total of 42 consecutive patients who underwent TACE and CRT (TACE+CRT group) for the treatment of HCC with IVCTT were prospectively enrolled from July 2004 to October 2006. As historical controls, 29 HCC patients with IVCTT who received TACE alone (TACE group) between July 2003 and June 2004 were included. CRT was designed to target only the IVCTT and to deliver a median total dose of 45 Gy (range,more » 28-50 Gy). Results: Most baseline characteristics of the two groups were similar (p > 0.05). The response and progression-free rates of IVCTT were significantly higher in the TACE+CRT group than in the TACE group (42.9% and 71.4% vs. 13.8% and 37.9%, respectively; p < 0.01 for both rates). Overall, patient survival was significantly higher in the TACE+CRT group than in the TACE group (p < 0.01), with a median survival time of 11.7 months and 4.7 months, respectively. Treatment with TACE+CRT (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.71), progression of IVCTT (HR = 4.05; 95% CI, 2.00-8.21), Child-Pugh class B (HR = 3.44; 95% CI, 1.79-6.61), and portal vein invasion (HR = 2.31; 95% CI, 1.19-4.50) were identified as independent predictors of mortality by multivariable analysis. Conclusions: The combination of TACE and CRT is more effective in the control of IVCTT associated with HCC and improves patient survival compared with TACE alone.« less

Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary?

PubMed

Zhao, Kuai-le; Ma, Jin-bo; Liu, Guang; Wu, Kai-liang; Shi, Xue-hui; Jiang, Guo-liang

2010-02-01

To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. Copyright 2010 Elsevier Inc. All rights reserved.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with static gantry IMRT and 3D conformal radiotherapy for advanced esophageal cancer: a feasibility study.

PubMed

Nicolini, Giorgia; Ghosh-Laskar, Sarbani; Shrivastava, Shyam Kishore; Banerjee, Sushovan; Chaudhary, Suresh; Agarwal, Jai Prakash; Munshi, Anusheel; Clivio, Alessandro; Fogliata, Antonella; Mancosu, Pietro; Vanetti, Eugenio; Cozzi, Luca

2012-10-01

A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving ≥ 95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving ≥ 5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 ± 0.1 for RA and IMRT and 1.5 ± 0.2 for 3D-CRT. The mean lung dose was 12.2 ± 4.5 for IMRT, 11.3 ± 4.6 for RA, and 10.8 ± 4.4 for RA with FFF beams, 18.2 ± 8.5 for 3D-CRT. The percentage of volume receiving ≥ 20 Gy ranged from 23.6% ± 9.1% to 21.1% ± 9.7% for IMRT and RA (FFF beams) and 39.2% ± 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 ± 139, 322 ± 20, and 387 ± 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a ∼20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different gantry speeds). RA demonstrated, compared with conventional IMRT, a similar target coverage and some better dose sparing to the organs at risk; the advantage against conventional 3D-CRT was more evident. RA with FFF beams resulted in minor improvements in plan quality but with the potential for additional useful reduction in the treatment time. Copyright © 2012 Elsevier Inc. All rights reserved.

Creating physically-based three-dimensional microstructures: Bridging phase-field and crystal plasticity models.

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

Lim, Hojun; Owen, Steven J.; Abdeljawad, Fadi F.

In order to better incorporate microstructures in continuum scale models, we use a novel finite element (FE) meshing technique to generate three-dimensional polycrystalline aggregates from a phase field grain growth model of grain microstructures. The proposed meshing technique creates hexahedral FE meshes that capture smooth interfaces between adjacent grains. Three dimensional realizations of grain microstructures from the phase field model are used in crystal plasticity-finite element (CP-FE) simulations of polycrystalline a -iron. We show that the interface conformal meshes significantly reduce artificial stress localizations in voxelated meshes that exhibit the so-called "wedding cake" interfaces. This framework provides a direct linkmore » between two mesoscale models - phase field and crystal plasticity - and for the first time allows mechanics simulations of polycrystalline materials using three-dimensional hexahedral finite element meshes with realistic topological features.« less

Quantum gravity in three dimensions, Witten spinors and the quantisation of length

NASA Astrophysics Data System (ADS)

Wieland, Wolfgang

2018-05-01

In this paper, I investigate the quantisation of length in euclidean quantum gravity in three dimensions. The starting point is the classical hamiltonian formalism in a cylinder of finite radius. At this finite boundary, a counter term is introduced that couples the gravitational field in the interior to a two-dimensional conformal field theory for an SU (2) boundary spinor, whose norm determines the conformal factor between the fiducial boundary metric and the physical metric in the bulk. The equations of motion for this boundary spinor are derived from the boundary action and turn out to be the two-dimensional analogue of the Witten equations appearing in Witten's proof of the positive mass theorem. The paper concludes with some comments on the resulting quantum theory. It is shown, in particular, that the length of a one-dimensional cross section of the boundary turns into a number operator on the Fock space of the theory. The spectrum of this operator is discrete and matches the results from loop quantum gravity in the spin network representation.

Baby de Sitter black holes and dS3/CFT2

NASA Astrophysics Data System (ADS)

de Buyl, Sophie; Detournay, Stéphane; Giribet, Gaston; Ng, Gim Seng

2014-02-01

Unlike three-dimensional Einstein gravity, three-dimensional massive gravity admits asymptotically de Sitter space (dS) black hole solutions. These black holes present interesting features and provide us with toy models to study the dS/CFT correspondence. A remarkable property of these black holes is that they are always in thermal equilibrium with the cosmological horizon of the space that hosts them. This invites us to study the thermodynamics of these solutions within the context of dS/CFT. We study the asymptotic symmetry group of the theory and find that it indeed coincides with the local two-dimensional conformal algebra. The charge algebra associated to the asymptotic Killing vectors consists of two copies of the Virasoro algebra with non-vanishing central extension. We compute the mass and angular momentum of the dS black holes and verify that a naive application of Cardy's formula exactly reproduces the entropy of both the black hole and the cosmological horizon. By adapting the holographic renormalization techniques to the case of dS space, we define the boundary stress tensor of the dual Euclidean conformal field theory.

Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

PubMed

Chen, Ming; Hayman, James A; Ten Haken, Randall K; Tatro, Daniel; Fernando, Shaneli; Kong, Feng-Ming

2006-01-01

To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

An Individualized 3-Dimensional Designed and Printed Conformer After Dermis Fat Grafting for Complex Sockets.

PubMed

Mourits, Daphne L; Remmers, Jelmer S; Tan, Stevie H; Moll, Annette C; Hartong, Dyonne T

2018-04-03

To introduce a novel technique to design individually customized conformers for postenucleation sockets with dermis fat implants. We use a 3-dimensional scan of the frontal face/orbit and eyelid contour to design an individualized conformer. This polymethylmetacrylate printed conformer is adapted to patients' socket, palpebral fissures, horizontal eyelid aperture, curvature of the eyelids, and mean diameter of patients' contralateral eye. Sutures through holes in the inferior part of the conformer and in the extension can be placed to fixate the conformer and anchor fornix deepening sutures. A correct fitting conformer can be printed and attached to the socket and eyelids. The shape of this conformer can be used subsequently postsurgically to design the ocular prosthesis. Presurgical planning is important to anticipate for a functional socket to adequately fit an artificial eye. The presented technique using 3-dimensional imaging, designing, and printing promises to prevent conformer extrusion and forniceal shortening.

Directly reconstructing principal components of heterogeneous particles from cryo-EM images.

PubMed

Tagare, Hemant D; Kucukelbir, Alp; Sigworth, Fred J; Wang, Hongwei; Rao, Murali

2015-08-01

Structural heterogeneity of particles can be investigated by their three-dimensional principal components. This paper addresses the question of whether, and with what algorithm, the three-dimensional principal components can be directly recovered from cryo-EM images. The first part of the paper extends the Fourier slice theorem to covariance functions showing that the three-dimensional covariance, and hence the principal components, of a heterogeneous particle can indeed be recovered from two-dimensional cryo-EM images. The second part of the paper proposes a practical algorithm for reconstructing the principal components directly from cryo-EM images without the intermediate step of calculating covariances. This algorithm is based on maximizing the posterior likelihood using the Expectation-Maximization algorithm. The last part of the paper applies this algorithm to simulated data and to two real cryo-EM data sets: a data set of the 70S ribosome with and without Elongation Factor-G (EF-G), and a data set of the influenza virus RNA dependent RNA Polymerase (RdRP). The first principal component of the 70S ribosome data set reveals the expected conformational changes of the ribosome as the EF-G binds and unbinds. The first principal component of the RdRP data set reveals a conformational change in the two dimers of the RdRP. Copyright © 2015 Elsevier Inc. All rights reserved.

Black-hole/near-horizon-CFT duality and 4 dimensional classical spacetimes

NASA Astrophysics Data System (ADS)

Rodriguez, Leo L.

2011-09-01

In this thesis we accomplish two goals: We construct a two dimensional conformal field theory (CFT), in the form of a Liouville theory, in the near horizon limit for three and four dimensions black holes. The near horizon CFT assumes the two dimensional black hole solutions that were first introduced by Christensen and Fulling (1977 Phys. Rev. D 15 2088-104) and later expanded to a greater class of black holes via Robinson and Wilczek (2005 Phys. Rev. Lett. 95 011303). The two dimensions black holes admit a Diff( S1) or Witt subalgebra, which upon quantization in the horizon limit becomes Virasoro with calculable central charge. These charges and lowest Virasoro eigen-modes reproduce the correct Bekenstein-Hawking entropy of the four and three dimensions black holes via the Cardy formula (Blote et al 1986 Phys. Rev. Lett. 56 742; Cardy 1986 Nucl. Phys. B 270 186). Furthermore, the two dimensions CFT's energy momentum tensor is anomalous, i.e. its trace is nonzero. However, In the horizon limit the energy momentum tensor becomes holomorphic equaling the Hawking flux of the four and three dimensions black holes. This encoding of both entropy and temperature provides a uniformity in the calculation of black hole thermodynamics and statistical quantities for the non local effective action approach. We also show that the near horizon regime of a Kerr-Newman-AdS (KNAdS) black hole, given by its two dimensional analogue a la Robinson and Wilczek, is asymptotically AdS 2 and dual to a one dimensional quantum conformal field theory (CFT). The s-wave contribution of the resulting CFT's energy-momentum-tensor together with the asymptotic symmetries, generate a centrally extended Virasoro algebra, whose central charge reproduces the Bekenstein-Hawking entropy via Cardy's Formula. Our derived central charge also agrees with the near extremal Kerr/CFT Correspondence in the appropriate limits. We also compute the Hawking temperature of the KNAdS black hole by coupling its Robinson and Wilczek two dimensional analogue (RW2DA) to conformal matter.

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

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Hiraoka, Masahiro

Purpose: To investigate the dosimetric advantage of intensity-modulated radiotherapy (IMRT) for whole ventricles (WV) in patients with a localized intracranial germinoma receiving induction chemotherapy. Methods and Materials: Data from 12 consecutive patients with localized intracranial germinomas who received induction chemotherapy and radiotherapy were used. Four-field coplanar three-dimensional conformal radiotherapy (3D-CRT) and seven-field coplanar IMRT plans were created. In both plans, 24 Gy was prescribed in 12 fractions for the planning target volume (PTV) involving WV and tumor bed. In IMRT planning, optimization was conducted to reduce the doses to the organs at risk (OARs) as much as possible, keeping themore » minimum dose equivalent to that of 3D-CRT. The 3D-CRT and IMRT plans were compared in terms of the dose-volume statistics for target coverage and the OARs. Results: IMRT significantly increased the percentage volume of the PTV receiving 24 Gy compared with 3D-CRT (93.5% vs. 84.8%; p = 0.007), while keeping target homogeneity equivalent to 3D-CRT (p = 0.869). The absolute percentage reduction in the irradiated volume of the normal brain receiving 100%, 75%, 50%, and 25% of 24 Gy ranged from 0.7% to 16.0% in IMRT compared with 3D-CRT (p < 0.001). No significant difference was observed in the volume of the normal brain receiving 10% and 5% of 24 Gy between IMRT and 3D-CRT. Conformation number was significantly improved in IMRT (p < 0.001). For other OARs, the mean dose to the cochlea was reduced significantly in IMRT by 22.3% of 24 Gy compared with 3D-CRT (p < 0.001). Conclusions: Compared with 3D-CRT, IMRT for WV improved the target coverage and reduced the irradiated volume of the normal brain in patients with intracranial germinomas receiving induction chemotherapy. IMRT for WV with induction chemotherapy could reduce the late side effects from cranial irradiation without compromising control of the tumor.« less

StructMap: Elastic Distance Analysis of Electron Microscopy Maps for Studying Conformational Changes.

PubMed

Sanchez Sorzano, Carlos Oscar; Alvarez-Cabrera, Ana Lucia; Kazemi, Mohsen; Carazo, Jose María; Jonić, Slavica

2016-04-26

Single-particle electron microscopy (EM) has been shown to be very powerful for studying structures and associated conformational changes of macromolecular complexes. In the context of analyzing conformational changes of complexes, distinct EM density maps obtained by image analysis and three-dimensional (3D) reconstruction are usually analyzed in 3D for interpretation of structural differences. However, graphic visualization of these differences based on a quantitative analysis of elastic transformations (deformations) among density maps has not been done yet due to a lack of appropriate methods. Here, we present an approach that allows such visualization. This approach is based on statistical analysis of distances among elastically aligned pairs of EM maps (one map is deformed to fit the other map), and results in visualizing EM maps as points in a lower-dimensional distance space. The distances among points in the new space can be analyzed in terms of clusters or trajectories of points related to potential conformational changes. The results of the method are shown with synthetic and experimental EM maps at different resolutions. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Theoretical investigation of the He4Br2 conformers.

PubMed

Valdés, Álvaro; Prosmiti, Rita; Villarreal, Pablo; Delgado-Barrio, Gerardo

2012-07-05

Full dimensional quantum dynamics calculations of the three lowest isomers of the He(4)Br(2) van der Waals molecule in its ground electronic state are reported. The calculations are performed using the multiconfiguration time-dependent Hartree (MCTDH) method and a realistic potential form that includes the sum of three body ab initio coupled-cluster single double triple [CCSD(T)] He-Br(2) interactions plus the He-He and Br-Br interactions. This potential exhibits several multiple minima, with the three lowest ones lying very close in energy, just within 2 cm(-1). Such small differences are also found in the calculated binding energies of the three most stable conformers, indicating the floppiness of the system and, thus, the need of accurate potential forms and quantum full dynamics methods to treat this kind of complexes. The 12 dimensional results reported in this work present benchmark data and, thus, can serve to evaluate approximate methods aiming to describe higher order rare gas-dihalogen (N > 4) complexes. A comparison with previous studies using different potential forms and approaches to the energetics for the He(4)Br(2) cluster is also presented.

A randomized controlled trial of conventional fraction and late course accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal cancer.

PubMed

Wang, Jian-Hua; Lu, Xu-Jing; Zhou, Jian; Wang, Feng

2012-01-01

We compared the curative and side-effects in esophageal carcinoma treated by conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three-dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned to two different radiotherapy model groups. Fifty patients were treated using CF three-dimensional conformal radiotherapy at a total dose of 60-68 Gy; 2 Gy/F; 5 fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF-treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21-27 Gy; a total dose of 61-67 Gy; median 64 Gy). The data showed that the 1-, 2- and 3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74, 54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P = 0.454). In CF group, the incidence of radiation-induced esophagitis was lower than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant difference between rates of radiation-induced pneumonitis in CF and LCAF groups (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local control and survival rates of esophageal carcinoma patients treated with LCAF were slightly better than CF radiotherapy; however, the radiation side-effects in LCAF group were greater than those in CF group.

Conformational analysis by intersection: CONAN.

PubMed

Smellie, Andrew; Stanton, Robert; Henne, Randy; Teig, Steve

2003-01-15

As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10-20, 2003

Enhanced conformational sampling technique provides an energy landscape view of large-scale protein conformational transitions.

PubMed

Shao, Qiang

2016-10-26

Large-scale conformational changes in proteins are important for their functions. Tracking the conformational change in real time at the level of a single protein molecule, however, remains a great challenge. In this article, we present a novel in silico approach with the combination of normal mode analysis and integrated-tempering-sampling molecular simulation (NMA-ITS) to give quantitative data for exploring the conformational transition pathway in multi-dimensional energy landscapes starting only from the knowledge of the two endpoint structures of the protein. The open-to-closed transitions of three proteins, including nCaM, AdK, and HIV-1 PR, were investigated using NMA-ITS simulations. The three proteins have varied structural flexibilities and domain communications in their respective conformational changes. The transition state structure in the conformational change of nCaM and the associated free-energy barrier are in agreement with those measured in a standard explicit-solvent REMD simulation. The experimentally measured transition intermediate structures of the intrinsically flexible AdK are captured by the conformational transition pathway measured here. The dominant transition pathways between the closed and fully open states of HIV-1 PR are very similar to those observed in recent REMD simulations. Finally, the evaluated relaxation times of the conformational transitions of three proteins are roughly at the same level as reported experimental data. Therefore, the NMA-ITS method is applicable for a variety of cases, providing both qualitative and quantitative insights into the conformational changes associated with the real functions of proteins.

5-Ethynyl-2'-deoxycytidine: a DNA building block with a 'clickable' side chain.

PubMed

Seela, Frank; Mei, Hui; Xiong, Hai; Budow, Simone; Eickmeier, Henning; Reuter, Hans

2012-10-01

The title compound [systematic name: 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-ethynylpyrimidin-2(1H)-one], C(11)H(13)N(3)O(4), shows two conformations in the crystalline state. The N-glycosylic bonds of both conformers adopt similar conformations, with χ = -149.2 (1)° for conformer (I-1) and -151.4 (1)° for conformer (I-2), both in the anti range. The sugar residue of (I-1) shows a C2'-endo envelope conformation ((2)E, S-type), with P = 164.7 (1)° and τ(m) = 36.9 (1)°, while (I-2) shows a major C3'-exo sugar pucker (C3'-exo-C2'-endo, (3)T(2), S-type), with P = 189.2 (1)° and τ(m) = 33.3 (1)°. Both conformers participate in the formation of a layered three-dimensional crystal structure with a chain-like arrangement of the conformers. The ethynyl groups do not participate in hydrogen bonding, but are arranged in proximal positions.

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

Hosseinizadeh, Ahmad; Mashayekhi, Ghoncheh; Copperman, Jeremy

Using a manifold-based analysis of experimental diffraction snapshots from an X-ray free electron laser, we determine the three-dimensional structure and conformational landscape of the PR772 virus to a detector-limited resolution of 9 nm. Our results indicate that a single conformational coordinate controls reorganization of the genome, growth of a tubular structure from a portal vertex and release of the genome. Furthermore, these results demonstrate that single-particle X-ray scattering has the potential to shed light on key biological processes.

In Silico Docking of Small-Molecule Inhibitors to the Escherichia coli Type III Secretion System EscN ATPase

DTIC Science & Technology

2014-07-01

coordinates of the EscN protein (Zarivach et al., 2007) were downloaded in pdb file format from the Research Collaboratory for Structural Biology...catalytic activity. Two structurally related compounds were observed to adopt extended conformations in the active-site cleft and essentially...adopt a very compact conformation that occupied only one side of the cleft. Our goal was to determine the three-dimensional structures of the

Exploring the Roles of Proline in Three-Dimensional Domain Swapping from Structure Analysis and Molecular Dynamics Simulations.

PubMed

Huang, Yongqi; Gao, Meng; Su, Zhengding

2018-02-01

Three-dimensional (3D) domain swapping is a mechanism to form protein oligomers. It has been proposed that several factors, including proline residues in the hinge region, may affect the occurrence of 3D domain swapping. Although introducing prolines into the hinge region has been found to promote domain swapping for some proteins, the opposite effect has also been observed in several studies. So far, how proline affects 3D domain swapping remains elusive. In this work, based on a large set of 3D domain-swapped structures, we performed a systematic analysis to explore the correlation between the presence of proline in the hinge region and the occurrence of 3D domain swapping. We further analyzed the conformations of proline and pre-proline residues to investigate the roles of proline in 3D domain swapping. We found that more than 40% of the domain-swapped structures contained proline residues in the hinge region. Unexpectedly, conformational transitions of proline residues were rarely observed upon domain swapping. Our analyses showed that hinge regions containing proline residues preferred more extended conformations, which may be beneficial for the occurrence of domain swapping by facilitating opening of the exchanged segments.

Conformal Nets II: Conformal Blocks

NASA Astrophysics Data System (ADS)

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.

Comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy in the treatment of cervical esophageal carcinoma.

PubMed

Yang, Hao; Feng, Cong; Cai, Bo-Ning; Yang, Jun; Liu, Hai-Xia; Ma, Lin

2017-02-01

The aim of this study was to evaluate the effectiveness and toxicities of three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) in patients with cervical esophageal cancer. Specifically, we asked whether technological advances conferred an advantage with respect to the clinical curative effect. Seventy-eight patients with cervical esophageal cancer treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2007 and 2014 were enrolled in the study: 26 received 3DCRT, 30 were treated with IMRT, and 22 underwent VMAT. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze overall survival (OS) and failure-free survival (FFS). Treatment-related toxicity was also assessed. For all patients, the 2-year OS and FFS rates were 56.2 and 53.9%, respectively. The 2-year OS for the 3DCRT, IMRT, and VMAT groups was 53.6, 55.6, and 60.6%, respectively (P = 0.965). The corresponding 2-year FFS rates were 49.5, 56.7, and 60.1% (P = 0.998). A univariate analysis of the complete response to treatment showed an advantage of treatment modality with respect to OS (P < 0.001). The development of acute hematologic toxicity was not significantly different among the three groups. The survival rates of patients treated with IMRT and VMAT were comparable to the survival of patients administered 3DCRT, while lower lung mean dose, V20, maximum dose of brachial plexus and spinal cord. Grade 1 radiation pneumonitis occurred significantly less in patients treated with IMRT and VMAT than with 3DCRT (P = 0.011). A complete response was the most important prognostic factor of the patients with cervical esophageal cancer. © 2016 International Society for Diseases of the Esophagus.

Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study.

PubMed

Li, Jingxia; Mu, Shuangfeng; Mu, Lixiang; Zhang, Xiaohui; Pang, Ranran; Gao, Shegan

2015-01-01

To examine the relationship between cytokine levels of transforming growth factor-beta-1 (TGF-β1), interleukin-1 beta (IL-1β), and angiotensin-converting enzyme (ACE) in the plasma of esophageal carcinoma patients and radiation-induced pneumonitis (RP). Sixty-three patients with esophageal carcinoma were treated with three-dimensional conformal radiotherapy (RT) using the Elekta Precise treatment planning system with a prescribed dose of 50-70 Gy. Dose-volume histograms were collected from three-dimensional conformal RT to determine the volume percentage of the lung received V5, V10, V20, and the normal tissue complication probability. RP was diagnosed based on computed tomography imaging, respiratory symptoms, and signs. The severity of radiation-induced lung toxicity was determined using the Lent-Soma scale defined by the Radiation Therapy Oncology Group. Plasma samples obtained before RT, during RT (at 40 Gy), and at 1 day, 1 month, and 3 months after RT were assayed for TGF-β1, IL-1β, and ACE levels by enzyme-linked immunosorbent assay. From the 63 patients, 17 (27%) developed RP, and 13 (21%) had RP of grade I and four (6%) had grade II or higher. We found plasma TGF-β1 levels were elevated in the patients that had RP when compared with the other 46 patients who did not have RP. The plasma IL-1β levels were not changed. The ACE levels were significantly lower in the 17 patients with RP compared to the 46 patients without RP throughout the RT. As expected, RP is associated with a higher dose of irradiation (>60 Gy); no other factors, including dose-volume histogram, age, sex, smoking status, location of tumor, and methods of treatment, are associated with RP. Elevated plasma TGF-β1 levels can be used as a marker for RP.

Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

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

Fang, F.-M.; Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan; Chien, C.-Y.

2008-10-01

Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research andmore » Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity.« less

Feasibility of tomotherapy to reduce normal lung and cardiac toxicity for distal esophageal cancer compared to three-dimensional radiotherapy.

PubMed

Nguyen, Nam P; Krafft, Shane P; Vinh-Hung, Vincent; Vos, Paul; Almeida, Fabio; Jang, Siyoung; Ceizyk, Misty; Desai, Anand; Davis, Rick; Hamilton, Russ; Modarresifar, Homayoun; Abraham, Dave; Smith-Raymond, Lexie

2011-12-01

To compare the effectiveness of tomotherapy and three-dimensional (3D) conformal radiotherapy to spare normal critical structures (spinal cord, lungs, and ventricles) from excessive radiation in patients with distal esophageal cancers. A retrospective dosimetric study of nine patients who had advanced gastro-esophageal (GE) junction cancer (7) or thoracic esophageal cancer (2) extending into the distal esophagus. Two plans were created for each of the patients. A three-dimensional plan was constructed with either three (anteroposterior, right posterior oblique, and left posterior oblique) or four (right anterior oblique, left anterior oblique, right posterior oblique, and left posterior oblique) fields. The second plan was for tomotherapy. Doses were 45 Gy to the PTV with an integrated boost of 5 Gy for tomotherapy. Mean lung dose was respectively 7.4 and 11.8 Gy (p=0.004) for tomotherapy and 3D plans. Corresponding values were 12.4 and 18.3 Gy (p=0.006) for cardiac ventricles. Maximum spinal cord dose was respectively 31.3 and 37.4 Gy (p < 0.007) for tomotherapy and 3D plans. Homogeneity index was two for both groups. Compared to 3D conformal radiotherapy, tomotherapy decreased significantly the amount of normal tissue irradiated and may reduce treatment toxicity for possible dose escalation in future prospective studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Amide I vibrational circular dichroism of dipeptide: Conformation dependence and fragment analysis

NASA Astrophysics Data System (ADS)

Choi, Jun-Ho; Cho, Minhaeng

2004-03-01

The amide I vibrational circular dichroic response of alanine dipeptide analog (ADA) was theoretically investigated and the density functional theory calculation and fragment analysis results are presented. A variety of vibrational spectroscopic properties, local and normal mode frequencies, coupling constant, dipole, and rotational strengths, are calculated by varying two dihedral angles determining the three-dimensional ADA conformation. Considering two monopeptide fragments separately, we show that the amide I vibrational circular dichroism of the ADA can be quantitatively predicted. For several representative conformations of the model ADA, vibrational circular dichroism spectra are calculated by using both the density functional theory calculation and fragment analysis methods.

Dimensionality of organizational justice in a call center context.

PubMed

Flint, Douglas; Haley, Lynn M; McNally, Jeffrey J

2012-04-01

Summary.-Employees in three call centers were surveyed about their perceptions of organizational justice. Four factors were measured: distributive justice, procedural justice, interpersonal justice, and informational justice. Structural equation modeling was employed to test whether a two-, three-, or four-factor model best fit the call center data. A three-factor model of distributive, procedural, and informational justice provided the best fit to these data. The three-factor model that showed the best fit does not conform to any of the more traditional models identified in the organizational justice literature. This implies that the context in which organizational justice is measured may play a role in identifying which justice factors are relevant to employees. Findings add to the empirical evidence on the dimensionality of organizational justice and imply that dimensionality of organizational justice is more context-dependent than previously thought.

Dimensionality of Social Influence.

ERIC Educational Resources Information Center

Stricker, Lawrence J.; Jackson, Douglas N.

The research reported in this study explores two problematic avenues of conformity research: (1) the widely assumed generality of diverse measures of group pressure, and (2) the dimensionality of conformity, anticonformity, and independence. These two conformity situations, present and nonpresent norm groups, used two tasks (an objective counting…

Black holes in six-dimensional conformal gravity

NASA Astrophysics Data System (ADS)

Lü, H.; Pang, Yi; Pope, C. N.

2013-05-01

We study conformally invariant theories of gravity in six dimensions. In four dimensions, there is a unique such theory that is polynomial in the curvature and its derivatives, namely, Weyl-squared, and furthermore all solutions of Einstein gravity are also solutions of the conformal theory. By contrast, in six dimensions there are three independent conformally invariant polynomial terms one could consider. There is a unique linear combination (up to overall scale) for which Einstein metrics are also solutions, and this specific theory forms the focus of our attention in this paper. We reduce the equations of motion for the most general spherically symmetric black hole to a single fifth-order differential equation. We obtain the general solution in the form of an infinite series, characterized by five independent parameters, and we show how a finite three-parameter truncation reduces to the already known Schwarzschild-AdS metric and its conformal scaling. We derive general results for the thermodynamics and the first law for the full five-parameter solutions. We also investigate solutions in extended theories coupled to conformally invariant matter, and in addition we derive some general results for conserved charges in cubic-curvature theories in arbitrary dimensions.

Holograms of Flat Space

NASA Astrophysics Data System (ADS)

Bagchi, Arjun; Grumiller, Daniel

2013-07-01

The holographic principle has a concrete realization in the Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence. If this principle is a true fact about quantum gravity then it must also hold beyond AdS/CFT. In this paper, we address specifically holographic field theory duals of gravitational theories in asymptotically flat spacetimes. We present some evidence of our recent conjecture that three-dimensional (3d) conformal Chern-Simons gravity (CSG) with flat space boundary conditions is dual to an extremal CFT.

Renormalizable Quantum Field Theories in the Large -n Limit

NASA Astrophysics Data System (ADS)

Guruswamy, Sathya

1995-01-01

In this thesis, we study two examples of renormalizable quantum field theories in the large-N limit. Chapter one is a general introduction describing physical motivations for studying such theories. In chapter two, we describe the large-N method in field theory and discuss the pioneering work of 't Hooft in large-N two-dimensional Quantum Chromodynamics (QCD). In chapter three we study a spherically symmetric approximation to four-dimensional QCD ('spherical QCD'). We recast spherical QCD into a bilocal (constrained) theory of hadrons which in the large-N limit is equivalent to large-N spherical QCD for all energy scales. The linear approximation to this theory gives an eigenvalue equation which is the analogue of the well-known 't Hooft's integral equation in two dimensions. This eigenvalue equation is a scale invariant one and therefore leads to divergences in the theory. We give a non-perturbative renormalization prescription to cure this and obtain a beta function which shows that large-N spherical QCD is asymptotically free. In chapter four, we review the essentials of conformal field theories in two and higher dimensions, particularly in the context of critical phenomena. In chapter five, we study the O(N) non-linear sigma model on three-dimensional curved spaces in the large-N limit and show that there is a non-trivial ultraviolet stable critical point at which it becomes conformally invariant. We study this model at this critical point on examples of spaces of constant curvature and compute the mass gap in the theory, the free energy density (which turns out to be a universal function of the information contained in the geometry of the manifold) and the two-point correlation functions. The results we get give an indication that this model is an example of a three-dimensional analogue of a rational conformal field theory. A conclusion with a brief summary and remarks follows at the end.

Sialyldisaccharide conformations: a molecular dynamics perspective

NASA Astrophysics Data System (ADS)

Selvin, Jeyasigamani F. A.; Priyadarzini, Thanu R. K.; Veluraja, Kasinadar

2012-04-01

Sialyldisaccharides are significant terminal components of glycoconjugates and their negative charge and conformation are extensively utilized in molecular recognition processes. The conformation and flexibility of four biologically important sialyldisaccharides [Neu5Acα(2-3)Gal, Neu5Acα(2-6)Gal, Neu5Acα(2-8)Neu5Ac and Neu5Acα(2-9)Neu5Ac] are studied using Molecular Dynamics simulations of 20 ns duration to deduce the conformational preferences of the sialyldisaccharides and the interactions which stabilize the conformations. This study clearly describes the possible conformational models of sialyldisaccharides deduced from 20 ns Molecular Dynamics simulations and our results confirm the role of water in the structural stabilization of sialyldisaccharides. An extensive analysis on the sialyldisaccharide structures available in PDB also confirms the conformational regions found by experiments are detected in MD simulations of 20 ns duration. The three dimensional structural coordinates for all the MD derived sialyldisaccharide conformations are deposited in the 3DSDSCAR database and these conformational models will be useful for glycobiologists and biotechnologists to understand the biological functions of sialic acid containing glycoconjugates.

Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

PubMed

Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

2014-01-01

Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

Improved Outcomes with Intensity Modulated Radiation Therapy Combined with Temozolomide for Newly Diagnosed Glioblastoma Multiforme

PubMed Central

Aherne, Noel J.; Benjamin, Linus C.; Horsley, Patrick J.; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M. R.; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S.; Lee, Yvonne L.; McKay, Michael J.; Shakespeare, Thomas P.

2014-01-01

Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM. PMID:24563782

Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen.

PubMed

Perri, Francesco; Pisconti, Salvatore; Conson, Manuel; Pacelli, Roberto; Della Vittoria Scarpati, Giuseppina; Gnoni, Antonio; D'Aniello, Carmine; Cavaliere, Carla; Licchetta, Antonella; Cella, Laura; Giuliano, Mario; Schiavone, Concetta; Falivene, Sara; Di Lorenzo, Giuseppe; Buonerba, Carlo; Ravo, Vincenzo; Muto, Paolo

2015-01-01

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma.

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

PubMed

Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

2017-01-01

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution.

PubMed

Chen, Yi-Jen; Liu, An; Han, Chunhui; Tsai, Peter T; Schultheiss, Timothy E; Pezner, Richard D; Vora, Nilesh; Lim, Dean; Shibata, Stephen; Kernstine, Kemp H; Wong, Jeffrey Y C

2007-01-01

We compare different radiotherapy techniques-helical tomotherapy (tomotherapy), step-and-shoot IMRT (IMRT), and 3-dimensional conformal radiotherapy (3DCRT)-for patients with mid-distal esophageal carcinoma on the basis of dosimetric analysis. Six patients with locally advanced mid-distal esophageal carcinoma were treated with neoadjuvant chemoradiation followed by surgery. Radiotherapy included 50 Gy to gross planning target volume (PTV) and 45 Gy to elective PTV in 25 fractions. Tomotherapy, IMRT, and 3DCRT plans were generated. Dose-volume histograms (DVHs), homogeneity index (HI), volumes of lung receiving more than 10, 15, or 20 Gy (V(10), V(15), V(20)), and volumes of heart receiving more than 30 or 45 Gy (V(30), V(45)) were determined. Statistical analysis was performed by paired t-tests. By isodose distributions and DVHs, tomotherapy plans showed sharper dose gradients, more conformal coverage, and better HI for both gross and elective PTVs compared with IMRT or 3DCRT plans. Mean V(20) of lung was significantly reduced in tomotherapy plans. However, tomotherapy and IMRT plans resulted in larger V(10) of lung compared to 3DCRT plans. The heart was significantly spared in tomotherapy and IMRT plans compared to 3DCRT plans in terms of V(30) and V(45). We conclude that tomotherapy plans are superior in terms of target conformity, dose homogeneity, and V(20) of lung.

Free energy surface of two- and three-dimensional transitions of Au 12 nanoclusters obtained by ab initio metadynamics

NASA Astrophysics Data System (ADS)

Santarossa, Gianluca; Vargas, Angelo; Iannuzzi, Marcella; Baiker, Alfons

2010-05-01

The description of the conformational space generated by metal nanoparticles is a fundamental issue for the study of their physicochemical properties. In this investigation, an exhaustive exploration and a unified view of the conformational space of a gold nanocluster is provided using a Au 12 cluster as an example. Such system is characterized by coexisting planar/quasiplanar and tridimensional conformations separated by high-energy barriers. The conformational space of Au 12 has been explored by means of Born-Oppenheimer ab initio metadynamics, i.e., a molecular dynamics simulation coupled with a history dependent potential to accelerate events that might occur on a long time scale compared to the time step used in the simulations (rare events). The sampled conformations have complex, in general not intuitive topologies that we have classified as planar/quasiplanar or tridimensional, belonging to different regions of the free energy surface. Three conformational free energy basins were identified, one for the planar/quasiplanar and two for the tridimensional structures. At thermodynamic equilibrium, the planar/quasi-planar and tridimensional conformations were found to coexist, to be fluxional and to be separated by high-free-energy barriers. The comparison between the free energy and the potential energy revealed the relevance of the entropic contribution in the equilibrium distribution of the conformations of the cluster.

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

NASA Astrophysics Data System (ADS)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

2015-12-01

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H2ndc) or 4,4‧-(hydroxymethylene)dibenzoic acid (H2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd2(2,6-ndc)2(bpp)(DMF)]·2DMF (1) and [Cd3(hmdb)3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional 'Lucky Clover' shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process.

The dynamic three-dimensional organization of the diploid yeast genome

PubMed Central

Kim, Seungsoo; Liachko, Ivan; Brickner, Donna G; Cook, Kate; Noble, William S; Brickner, Jason H; Shendure, Jay; Dunham, Maitreya J

2017-01-01

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it is unclear how homolog pairing in diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation using a polymer model, we observe significant homolog proximity that increases in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1-TDA1 alleles specifically under galactose induction and saturated growth. This pairing is accompanied by relocalization to the nuclear periphery and requires Nup2, suggesting a role for nuclear pore complexes. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization. DOI: http://dx.doi.org/10.7554/eLife.23623.001 PMID:28537556

A genome-wide 3C-method for characterizing the three-dimensional architectures of genomes.

PubMed

Duan, Zhijun; Andronescu, Mirela; Schutz, Kevin; Lee, Choli; Shendure, Jay; Fields, Stanley; Noble, William S; Anthony Blau, C

2012-11-01

Accumulating evidence demonstrates that the three-dimensional (3D) organization of chromosomes within the eukaryotic nucleus reflects and influences genomic activities, including transcription, DNA replication, recombination and DNA repair. In order to uncover structure-function relationships, it is necessary first to understand the principles underlying the folding and the 3D arrangement of chromosomes. Chromosome conformation capture (3C) provides a powerful tool for detecting interactions within and between chromosomes. A high throughput derivative of 3C, chromosome conformation capture on chip (4C), executes a genome-wide interrogation of interaction partners for a given locus. We recently developed a new method, a derivative of 3C and 4C, which, similar to Hi-C, is capable of comprehensively identifying long-range chromosome interactions throughout a genome in an unbiased fashion. Hence, our method can be applied to decipher the 3D architectures of genomes. Here, we provide a detailed protocol for this method. Published by Elsevier Inc.

The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation.

PubMed

Umbarger, Mark A; Toro, Esteban; Wright, Matthew A; Porreca, Gregory J; Baù, Davide; Hong, Sun-Hae; Fero, Michael J; Zhu, Lihua J; Marti-Renom, Marc A; McAdams, Harley H; Shapiro, Lucy; Dekker, Job; Church, George M

2011-10-21

We have determined the three-dimensional (3D) architecture of the Caulobacter crescentus genome by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling. Using chromosome conformation capture carbon copy (5C), we derive ~13 kb resolution 3D models of the Caulobacter genome. The resulting models illustrate that the genome is ellipsoidal with periodically arranged arms. The parS sites, a pair of short contiguous sequence elements known to be involved in chromosome segregation, are positioned at one pole, where they anchor the chromosome to the cell and contribute to the formation of a compact chromatin conformation. Repositioning these elements resulted in rotations of the chromosome that changed the subcellular positions of most genes. Such rotations did not lead to large-scale changes in gene expression, indicating that genome folding does not strongly affect gene regulation. Collectively, our data suggest that genome folding is globally dictated by the parS sites and chromosome segregation. Copyright © 2011 Elsevier Inc. All rights reserved.

Fitting Multimeric Protein Complexes into Electron Microscopy Maps Using 3D Zernike Descriptors

PubMed Central

Esquivel-Rodríguez, Juan; Kihara, Daisuke

2012-01-01

A novel computational method for fitting high-resolution structures of multiple proteins into a cryoelectron microscopy map is presented. The method named EMLZerD generates a pool of candidate multiple protein docking conformations of component proteins, which are later compared with a provided electron microscopy (EM) density map to select the ones that fit well into the EM map. The comparison of docking conformations and the EM map is performed using the 3D Zernike descriptor (3DZD), a mathematical series expansion of three-dimensional functions. The 3DZD provides a unified representation of the surface shape of multimeric protein complex models and EM maps, which allows a convenient, fast quantitative comparison of the three dimensional structural data. Out of 19 multimeric complexes tested, near native complex structures with a root mean square deviation of less than 2.5 Å were obtained for 14 cases while medium range resolution structures with correct topology were computed for the additional 5 cases. PMID:22417139

Fitting multimeric protein complexes into electron microscopy maps using 3D Zernike descriptors.

PubMed

Esquivel-Rodríguez, Juan; Kihara, Daisuke

2012-06-14

A novel computational method for fitting high-resolution structures of multiple proteins into a cryoelectron microscopy map is presented. The method named EMLZerD generates a pool of candidate multiple protein docking conformations of component proteins, which are later compared with a provided electron microscopy (EM) density map to select the ones that fit well into the EM map. The comparison of docking conformations and the EM map is performed using the 3D Zernike descriptor (3DZD), a mathematical series expansion of three-dimensional functions. The 3DZD provides a unified representation of the surface shape of multimeric protein complex models and EM maps, which allows a convenient, fast quantitative comparison of the three-dimensional structural data. Out of 19 multimeric complexes tested, near native complex structures with a root-mean-square deviation of less than 2.5 Å were obtained for 14 cases while medium range resolution structures with correct topology were computed for the additional 5 cases.

SA-Search: a web tool for protein structure mining based on a Structural Alphabet

PubMed Central

Guyon, Frédéric; Camproux, Anne-Claude; Hochez, Joëlle; Tufféry, Pierre

2004-01-01

SA-Search is a web tool that can be used to mine for protein structures and extract structural similarities. It is based on a hidden Markov model derived Structural Alphabet (SA) that allows the compression of three-dimensional (3D) protein conformations into a one-dimensional (1D) representation using a limited number of prototype conformations. Using such a representation, classical methods developed for amino acid sequences can be employed. Currently, SA-Search permits the performance of fast 3D similarity searches such as the extraction of exact words using a suffix tree approach, and the search for fuzzy words viewed as a simple 1D sequence alignment problem. SA-Search is available at http://bioserv.rpbs.jussieu.fr/cgi-bin/SA-Search. PMID:15215446

SA-Search: a web tool for protein structure mining based on a Structural Alphabet.

PubMed

Guyon, Frédéric; Camproux, Anne-Claude; Hochez, Joëlle; Tufféry, Pierre

2004-07-01

SA-Search is a web tool that can be used to mine for protein structures and extract structural similarities. It is based on a hidden Markov model derived Structural Alphabet (SA) that allows the compression of three-dimensional (3D) protein conformations into a one-dimensional (1D) representation using a limited number of prototype conformations. Using such a representation, classical methods developed for amino acid sequences can be employed. Currently, SA-Search permits the performance of fast 3D similarity searches such as the extraction of exact words using a suffix tree approach, and the search for fuzzy words viewed as a simple 1D sequence alignment problem. SA-Search is available at http://bioserv.rpbs.jussieu.fr/cgi-bin/SA-Search.

Three-Dimensional Solid-State Lithium-Ion Batteries Fabricated by Conformal Vapor-Phase Chemistry.

PubMed

Pearse, Alexander; Schmitt, Thomas; Sahadeo, Emily; Stewart, David M; Kozen, Alexander; Gerasopoulos, Konstantinos; Talin, A Alec; Lee, Sang Bok; Rubloff, Gary W; Gregorczyk, Keith E

2018-05-22

Three-dimensional thin-film solid-state batteries (3D TSSB) were proposed by Long et al. in 2004 as a structure-based approach to simultaneously increase energy and power densities. Here, we report experimental realization of fully conformal 3D TSSBs, demonstrating the simultaneous power-and-energy benefits of 3D structuring. All active battery components-electrodes, solid electrolyte, and current collectors-were deposited by atomic layer deposition (ALD) onto standard CMOS processable silicon wafers microfabricated to form arrays of deep pores with aspect ratios up to approximately 10. The cells utilize an electrochemically prelithiated LiV 2 O 5 cathode, a very thin (40-100 nm) Li 2 PO 2 N solid electrolyte, and a SnN x anode. The fabrication process occurs entirely at or below 250 °C, promising compatibility with a variety of substrates as well as integrated circuits. The multilayer battery structure enabled all-ALD solid-state cells to deliver 37 μAh/cm 2 ·μm (normalized to cathode thickness) with only 0.02% per-cycle capacity loss. Conformal fabrication of full cells over 3D substrates increased the areal discharge capacity by an order of magnitude while simulteneously improving power performance, a trend consistent with a finite element model. This work shows that the exceptional conformality of ALD, combined with conventional semiconductor fabrication methods, provides an avenue for the successful realization of long-sought 3D TSSBs which provide power performance scaling in regimes inaccessible to planar form factor cells.

Conformational Effects through Hydrogen Bonding in a Constrained γ-Peptide Template: From Intraresidue Seven-Membered Rings to a Gel-Forming Sheet Structure.

PubMed

Awada, Hawraà; Grison, Claire M; Charnay-Pouget, Florence; Baltaze, Jean-Pierre; Brisset, François; Guillot, Régis; Robin, Sylvie; Hachem, Ali; Jaber, Nada; Naoufal, Daoud; Yazbeck, Ogaritte; Aitken, David J

2017-05-05

A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels. In the solid state, the dipeptide adopted a fully extended conformation featuring a one-dimensional network of intermolecularly H-bonded molecules stacked in an antiparallel sheet alignment. This work provides unique insight into the interplay between inter- and intramolecular H-bonded conformer topologies for the same peptide template.

Surface Design Based on Discrete Conformal Transformations

NASA Astrophysics Data System (ADS)

Duque, Carlos; Santangelo, Christian; Vouga, Etienne

Conformal transformations are angle-preserving maps from one domain to another. Although angles are preserved, the lengths between arbitrary points are not generally conserved. As a consequence there is always a given amount of distortion associated to any conformal map. Different uses of such transformations can be found in various fields, but have been used by us to program non-uniformly swellable gel sheets to buckle into prescribed three dimensional shapes. In this work we apply circle packings as a kind of discrete conformal map in order to find conformal maps from the sphere to the plane that can be used as nearly uniform swelling patterns to program non-Euclidean sheets to buckle into spheres. We explore the possibility of tuning the area distortion to fit the experimental range of minimum and maximum swelling by modifying the boundary of the planar domain through the introduction of different cutting schemes.

UV conformal window for asymptotic safety

NASA Astrophysics Data System (ADS)

Bond, Andrew D.; Litim, Daniel F.; Vazquez, Gustavo Medina; Steudtner, Tom

2018-02-01

Interacting fixed points in four-dimensional gauge theories coupled to matter are investigated using perturbation theory up to three loop order. It is shown how fixed points, scaling exponents, and anomalous dimensions are obtained as a systematic power series in a small parameter. The underlying ordering principle is explained and contrasted with conventional perturbation theory and Weyl consistency conditions. We then determine the conformal window with asymptotic safety from the complete next-to-next-to-leading order in perturbation theory. Limits for the conformal window arise due to fixed point mergers, the onset of strong coupling, or vacuum instability. A consistent picture is uncovered by comparing various levels of approximation. The theory remains perturbative in the entire conformal window, with vacuum stability dictating the tightest constraints. We also speculate about a secondary conformal window at strong coupling and estimate its lower limit. Implications for model building and cosmology are indicated.

Structure of GroEL in Complex with an Early Folding Intermediate of Alanine Glyoxylate Aminotransferase*

PubMed Central

Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Álvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

2010-01-01

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism. PMID:20056599

Structure of GroEL in complex with an early folding intermediate of alanine glyoxylate aminotransferase.

PubMed

Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Alvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

2010-02-26

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism.

Multiple Conformational States Contribute to the 3D Structure of a Glucan Decasaccharide: A Combined SAXS and MD Simulation Study.

PubMed

Jo, Sunhwan; Myatt, Daniel; Qi, Yifei; Doutch, James; Clifton, Luke A; Im, Wonpil; Widmalm, Göran

2018-01-25

The inherent flexibility of carbohydrates is dependent on stereochemical arrangements, and characterization of their influence and importance will give insight into the three-dimensional structure and dynamics. In this study, a β-(1→4)/β-(1→3)-linked glucosyl decasaccharide is experimentally investigated by synchrotron small-angle X-ray scattering from which its radius of gyration (R g ) is obtained. Molecular dynamics (MD) simulations of the decasaccharide show four populated states at each glycosidic linkage, namely, syn- and anti-conformations. The calculated R g values from the MD simulation reveal that in addition to syn-conformers the presence of anti-ψ conformational states is required to reproduce experimental scattering data, unveiling inherent glycosidic linkage flexibility. The CHARMM36 force field for carbohydrates thus describes the conformational flexibility of the decasaccharide very well and captures the conceptual importance that anti-conformers are to be anticipated at glycosidic linkages of carbohydrates.

Correlation functions of warped CFT

NASA Astrophysics Data System (ADS)

Song, Wei; Xu, Jianfei

2018-04-01

Warped conformal field theory (WCFT) is a two dimensional quantum field theory whose local symmetry algebra consists of a Virasoro algebra and a U(1) Kac-Moody algebra. In this paper, we study correlation functions for primary operators in WCFT. Similar to conformal symmetry, warped conformal symmetry is very constraining. The form of the two and three point functions are determined by the global warped conformal symmetry while the four point functions can be determined up to an arbitrary function of the cross ratio. The warped conformal bootstrap equation are constructed by formulating the notion of crossing symmetry. In the large central charge limit, four point functions can be decomposed into global warped conformal blocks, which can be solved exactly. Furthermore, we revisit the scattering problem in warped AdS spacetime (WAdS), and give a prescription on how to match the bulk result to a WCFT retarded Green's function. Our result is consistent with the conjectured holographic dualities between WCFT and WAdS.

Integrability of conformal fishnet theory

NASA Astrophysics Data System (ADS)

Gromov, Nikolay; Kazakov, Vladimir; Korchemsky, Gregory; Negro, Stefano; Sizov, Grigory

2018-01-01

We study integrability of fishnet-type Feynman graphs arising in planar four-dimensional bi-scalar chiral theory recently proposed in arXiv:1512.06704 as a special double scaling limit of gamma-deformed N = 4 SYM theory. We show that the transfer matrix "building" the fishnet graphs emerges from the R-matrix of non-compact conformal SU(2 , 2) Heisenberg spin chain with spins belonging to principal series representations of the four-dimensional conformal group. We demonstrate explicitly a relationship between this integrable spin chain and the Quantum Spectral Curve (QSC) of N = 4 SYM. Using QSC and spin chain methods, we construct Baxter equation for Q-functions of the conformal spin chain needed for computation of the anomalous dimensions of operators of the type tr( ϕ 1 J ) where ϕ 1 is one of the two scalars of the theory. For J = 3 we derive from QSC a quantization condition that fixes the relevant solution of Baxter equation. The scaling dimensions of the operators only receive contributions from wheel-like graphs. We develop integrability techniques to compute the divergent part of these graphs and use it to present the weak coupling expansion of dimensions to very high orders. Then we apply our exact equations to calculate the anomalous dimensions with J = 3 to practically unlimited precision at any coupling. These equations also describe an infinite tower of local conformal operators all carrying the same charge J = 3. The method should be applicable for any J and, in principle, to any local operators of bi-scalar theory. We show that at strong coupling the scaling dimensions can be derived from semiclassical quantization of finite gap solutions describing an integrable system of noncompact SU(2 , 2) spins. This bears similarities with the classical strings arising in the strongly coupled limit of N = 4 SYM.

The Holographic F Theorem

NASA Astrophysics Data System (ADS)

Taylor, Marika; Woodhead, William

2017-12-01

The F theorem states that, for a unitary three dimensional quantum field theory, the F quantity defined in terms of the partition function on a three sphere is positive, stationary at fixed point and decreases monotonically along a renormalization group flow. We construct holographic renormalization group flows corresponding to relevant deformations of three-dimensional conformal field theories on spheres, working to quadratic order in the source. For these renormalization group flows, the F quantity at the IR fixed point is always less than F at the UV fixed point, but F increases along the RG flow for deformations by operators of dimension between 3/2 and 5/2. Therefore the strongest version of the F theorem is in general violated.

9-(3,4-Dimeth-oxy-phen-yl)-3,4,5,6,7,9-hexa-hydroxanthene-1,8(2H)-dione.

PubMed

Mehdi, Sayed Hasan; Hashim, Rokiah; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-06-01

In the title compound, C(21)H(22)O(5), the mean planes of the pyran and dimeth-oxy-phenyl rings are nearly perpendicular to one another, with the dihedral angle between them being 88.21 (8)°. The pyran ring adopts a boat conformation whereas the two fused cyclo-hexane rings adopt envelope conformations. In the crystal, mol-ecules are linked into a three-dimensional network by inter-molecular C-H⋯O hydrogen bonds.

Indoor high precision three-dimensional positioning system based on visible light communication using modified genetic algorithm

NASA Astrophysics Data System (ADS)

Chen, Hao; Guan, Weipeng; Li, Simin; Wu, Yuxiang

2018-04-01

To improve the precision of indoor positioning and actualize three-dimensional positioning, a reversed indoor positioning system based on visible light communication (VLC) using genetic algorithm (GA) is proposed. In order to solve the problem of interference between signal sources, CDMA modulation is used. Each light-emitting diode (LED) in the system broadcasts a unique identity (ID) code using CDMA modulation. Receiver receives mixed signal from every LED reference point, by the orthogonality of spreading code in CDMA modulation, ID information and intensity attenuation information from every LED can be obtained. According to positioning principle of received signal strength (RSS), the coordinate of the receiver can be determined. Due to system noise and imperfection of device utilized in the system, distance between receiver and transmitters will deviate from the real value resulting in positioning error. By introducing error correction factors to global parallel search of genetic algorithm, coordinates of the receiver in three-dimensional space can be determined precisely. Both simulation results and experimental results show that in practical application scenarios, the proposed positioning system can realize high precision positioning service.

Commentary on "Patient-reported outcomes after 3-dimensional conformal, intensity-modulated, or proton beam radiotherapy for localized prostate cancer." Gray PJ, Paly JJ, Yeap BY, Sanda MG, Sandler HM, Michalski JM, Talcott JA, Coen JJ, Hamstra DA, Shipley WU, Hahn SM, Zietman AL, Bekelman JE, Efstathiou JA. Harvard Radiation Oncology Program, Boston, MA.: Cancer 2013;119(9):1729-35. doi: 10.1002/cncr.27956. [Epub 2013 Feb 22].

PubMed

Gottschalk, Alexander

2014-04-01

Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam therapy (PBT). The authors reviewed patient-reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the baseline mean value. Changes from baseline were compared within groups at the first post-treatment follow-up (2-3 months from the start of treatment) and at 12 months and 24 months. At the first post-treatment follow-up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post-treatment follow-up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL. Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment-related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences. © 2013 Published by Elsevier Inc.

Three-Dimensional Messages for Interstellar Communication

NASA Astrophysics Data System (ADS)

Vakoch, Douglas A.

One of the challenges facing independently evolved civilizations separated by interstellar distances is to communicate information unique to one civilization. One commonly proposed solution is to begin with two-dimensional pictorial representations of mathematical concepts and physical objects, in the hope that this will provide a foundation for overcoming linguistic barriers. However, significant aspects of such representations are highly conventional, and may not be readily intelligible to a civilization with different conventions. The process of teaching conventions of representation may be facilitated by the use of three-dimensional representations redundantly encoded in multiple formats (e.g., as both vectors and as rasters). After having illustrated specific conventions for representing mathematical objects in a three-dimensional space, this method can be used to describe a physical environment shared by transmitter and receiver: a three-dimensional space defined by the transmitter--receiver axis, and containing stars within that space. This method can be extended to show three-dimensional representations varying over time. Having clarified conventions for representing objects potentially familiar to both sender and receiver, novel objects can subsequently be depicted. This is illustrated through sequences showing interactions between human beings, which provide information about human behavior and personality. Extensions of this method may allow the communication of such culture-specific features as aesthetic judgments and religious beliefs. Limitations of this approach will be noted, with specific reference to ETI who are not primarily visual.

Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer.

PubMed

Freytag, Svend O; Stricker, Hans; Pegg, Jan; Paielli, Dell; Pradhan, Deepak G; Peabody, James; DePeralta-Venturina, Mariza; Xia, Xueqing; Brown, Steve; Lu, Mei; Kim, Jae Ho

2003-11-01

The primary study objective was to determine the safety of intraprostatic administration of a replication-competent, oncolytic adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene concomitant with increasing durations of 5-fluorocytosine and valganciclovir prodrug therapy and conventional-dose three-dimensional conformal radiation therapy (3D-CRT) in patients with newly diagnosed, intermediate- to high-risk prostate cancer. Secondary objectives were to determine the persistence of therapeutic transgene expression in the prostate and to examine early posttreatment response. Fifteen patients in five cohorts received a single intraprostatic injection of 10(12) viral particles of the replication-competent Ad5-CD/TKrep adenovirus on day 1. Two days later, patients were administered 5-fluorocytosine and valganciclovir prodrug therapy for 1 (cohorts 1-3), 2 (cohort 4), or 3 (cohort 5) weeks along with 70-74 Gy 3D-CRT. Sextant needle biopsy of the prostate was obtained at 2 (cohort 1), 3 (cohort 2), and 4 (cohort 3) weeks for determination of the persistence of transgene expression. There were no dose-limiting toxicities and no significant treatment-related adverse events. Ninety-four percent of the adverse events observed were mild to moderate and self-limiting. Acute urinary and gastrointestinal toxicities were similar to those expected for conventional-dose 3D-CRT. Therapeutic transgene expression was found to persist in the prostate for up to 3 weeks after the adenovirus injection. As expected for patients receiving definitive radiation therapy, all patients experienced significant declines in prostate-specific antigen (PSA). The mean PSA half-life in patients administered more than 1 week of prodrug therapy was significantly shorter than that of patients receiving prodrugs for only 1 week (0.6 versus 2.0 months; P < 0.02) and markedly shorter than that reported previously for patients treated with conventional-dose 3D-CRT alone (2.4 months). With a median follow-up of only 9 months, 5 of 10 (50%) patients not treated with androgen-deprivation therapy achieved a serum PSA < or = 0.5 ng/ml. The results demonstrate that replication-competent adenovirus-mediated double-suicide gene therapy can be combined safely with conventional-dose 3D-CRT in patients with intermediate- to high-risk prostate cancer. The shorter than expected PSA half-life in patients receiving more than 1 week of prodrug therapy may suggest a possible interaction between the oncolytic adenovirus and/or double-suicide gene therapies and radiation therapy.

Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams.

PubMed

Bahri, S; Flickinger, J C; Kalend, A M; Deutsch, M; Belani, C P; Sciurba, F C; Luketich, J D; Greenberger, J S

1999-01-01

A five-field conformal technique with three-dimensional radiation therapy treatment planning (3-DRTP) has been shown to permit better definition of the target volume for lung cancer, while minimizing the normal tissue volume receiving greater than 50% of the target dose. In an initial study to confirm the safety of conventional doses, we used the five-field conformal 3-DRTP technique. We then used the technique in a second study, enhancing the therapeutic index in a series of 42 patients, as well as to evaluate feasibility, survival outcome, and treatment toxicity. Forty-two consecutive patients with nonsmall-cell lung carcinoma (NSCLC) were evaluated during the years 1993-1997. The median age was 60 years (range 34-80). The median radiation therapy (RT) dose to the gross tumor volume was 6,300 cGy (range 5,000-6,840 cGy) delivered over 6 to 6.5 weeks in 180-275 cGy daily fractions, 5 days per week. There were three patients who received a split course treatment of 5,500 cGy in 20 fractions, delivering 275 cGy daily with a 2-week break built into the treatment course after 10 fractions. The stages of disease were II in 2%, IIIA in 40%, IIIB in 42.9%, and recurrent disease in 14.3% of the patients. The mean tumor volume was 324.14 cc (range 88.3-773.7 cc); 57.1% of the patients received combined chemoradiotherapy, while the others were treated with radiation therapy alone. Of the 42 patients, 7 were excluded from the final analysis because of diagnosis of distant metastasis during treatment. Two of the patients had their histology reinterpreted as being other than NSCLC, 2 patients did not complete RT at the time of analysis, and 1 patient voluntarily discontinued treatment because of progressive deterioration. Median follow-up was 11.2 months (range 3-32.5 months). Survival for patients with Stage III disease was 70.2% at 1 year and 51.5% at 2 years, with median survival not yet reached. Local control for the entire series was 23.3+/-11.4% at 2 years. However, for Stage III patients, local control was 50% at 1 year and 30% at 2 years. Patients who received concurrent chemotherapy had significantly improved survival (P = 0.002) and local control (P = 0.004), compared with RT alone. Late esophageal toxicity of > or =Grade 3 occurred in 14.1+/-9.3% of patients (3 of 20) receiving combined chemoradiotherapy, but in none of the 15 patients treated with RT alone. Pulmonary toxicity limited to Grades 1-2 occurred in 6.8% of the patients, and none developed > or =Grade 3 pulmonary toxicity. Patients with locally advanced NSCLC, who commonly have tumor volumes in excess of 200 cc, presenta challenge for adequate dose delivery without significant toxicity. Our five-field conformal 3-DRTP technique, which incorporates treatment planning by dose/volume histogram (DVH) was associated with minimal toxicity and may facilitate dose escalation to the gross tumor.

SU-F-P-52: A Meta-Analysis of Controlled Clinical Trials Comparing Elective Nodal Irradiation with Involved-Field Irradiation for Conformal Or Intensity-Modulated Radiotherapy in Patients with Esophageal Cancer

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

Bai, W; Zhang, R; Zhou, Z

Purpose: To compare elective nodal irradiation with involved-field irradiation for three-dimensional conformal radiotherapy or intensity-modulated radiotherapy in patients with esophageal cancer by a metaanalysis. Methods: Wanfang, CNKI, VIP, CBM databases, PubMed, Embase and Cochrane Library were searched to identify the controlled clinical trials of elective nodal irradiation with involved-field irradiation for three-dimensional conformal radiotherapy or intensity-modulated radiotherapy in patients with esophageal cancer. The obtained data were analyzed using Stata 11.0. The difference between two groups was estimated by calculating the odds ratio (OR) with 95% confidence interval (95% CI). Results: A total of 12 controlled clinical trials involving 1095 esophagealmore » cancer patients, which were selected according to inclusion and exclusion criteria, were included in this meta-analysis. The meta-analysis showed that the elective nodal irradiation group reduced the rates of out-field failure comparing with involved-field irradiation group (OR=3.727, P=0.007). However, the rates of ≥grades 3 acute radiation pneumonitis and esophagitis were significantly higher in the elective nodal irradiation group than in the involved-field irradiation group (OR=0.348, P=0.001, OR=0.385, P=0.000). 1-, 2-, 3-year local control rates (OR=0.966, P=0.837, OR=0.946, P=0.781; OR=0.732P=0.098) and 1-, 3-, 5-year survival rates were similar in the two groups ( OR=0.966, P=0.837; OR=0.946, P=0.781; OR=0.732, P=0.098; OR=0.952, P=0.756; OR=1.149, P=0.422; OR=0.768, P=0.120). It is the same with the rates of distant metastasis (OR=0.986, P=0.937). Conclusion: Compared with involved-field irradiation, the elective nodal irradiation can reduce the rates of out-field failure for three-dimensional conformal radiotherapy or intensity-modulated radiotherapy in patients with esophageal cancer. However, its advantage of local control and survival rates is not obvious and it increases the incidence of toxicities.« less

Structures of Rotavirus Reassortants Demonstrate Correlation of Altered Conformation of the VP4 Spike and Expression of Unexpected VP4-Associated Phenotypes

PubMed Central

Pesavento, Joseph B.; Billingsley, Angela M.; Roberts, Ed J.; Ramig, Robert F.; Prasad, B. V. Venkataram

2003-01-01

Numerous prior studies have indicated that viable rotavirus reassortants containing structural proteins of heterologous parental origin may express unexpected phenotypes, such as changes in infectivity and immunogenicity. To provide a structural basis for alterations in phenotypic expression, a three-dimensional structural analysis of these reassortants was conducted. The structures of the reassortants show that while VP4 generally maintains the parental structure when moved to a heterologous protein background, in certain reassortants, there are subtle alterations in the conformation of VP4. The alterations in VP4 conformation correlated with expression of unexpected VP4-associated phenotypes. Interactions between heterologous VP4 and VP7 in reassortants expressing unexpected phenotypes appeared to induce the conformational alterations seen in VP4. PMID:12584352

Thermally induced conformational changes in polyethylene studied by two-dimensional near-infrared infrared hetero-spectral correlation spectroscopy

NASA Astrophysics Data System (ADS)

Watanabe, Shin; Noda, Isao; Ozaki, Yukihiro

2008-07-01

The amount of nonplanar gauche bonds was monitored as a function of increasing temperature in three different polyethylene (PE) samples by means of mid-infrared (MIR) and near-infrared (NIR) spectroscopy. The hetero-spectral two-dimensional (2D) correlation analysis was carried out between the NIR spectral region of 4365-4235 cm -1 and the well-established MIR spectral region of 1375-1265 cm -1, where bands due to nonplanar conformer are detected. This approach allowed us to identify the NIR band at 4265 cm -1, which behaves in a way similar to MIR bands originating from conformational-defect sequences. By combining the result of our current study and that of our previous report obtained on different types of PE, it is suggested that the NIR band originates from conformational-defect sequences in PE. This finding opens up a unique and useful way to study the state of conformational disorder in PE crystal by NIR spectroscopy, monitoring the intensity of the NIR band at 4265 cm -1. The use of NIR spectroscopy allows researchers to directly probe the degree in the formation of conformational-defect sequences in thick, real-world PE samples that cannot be studied by conventional MIR spectroscopy. The 2D correlation spectroscopy analysis among the MIR CH 2 wagging conformational-defect-mode bands on linear low-density PE (LLDPE) and low-density PE (LDPE) revealed the formation of nonplanar conformer represented by the band at 1368 cm -1 proceeds prior to those by other band at 1308 cm -1. This result agrees well with our previous finding on high-density PE (HDPE). We therefore propose with strong confidence that the bands at 1368 and 1308 cm -1 arise from different conformational-defect sequences, even though both of the bands have been proposed to arise from the same conformer of gtg' ( kink) + gtg sequence.

Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3.

PubMed

Diehl, Carl; Engström, Olof; Delaine, Tamara; Håkansson, Maria; Genheden, Samuel; Modig, Kristofer; Leffler, Hakon; Ryde, Ulf; Nilsson, Ulf J; Akke, Mikael

2010-10-20

Rational drug design is predicated on knowledge of the three-dimensional structure of the protein-ligand complex and the thermodynamics of ligand binding. Despite the fundamental importance of both enthalpy and entropy in driving ligand binding, the role of conformational entropy is rarely addressed in drug design. In this work, we have probed the conformational entropy and its relative contribution to the free energy of ligand binding to the carbohydrate recognition domain of galectin-3. Using a combination of NMR spectroscopy, isothermal titration calorimetry, and X-ray crystallography, we characterized the binding of three ligands with dissociation constants ranging over 2 orders of magnitude. (15)N and (2)H spin relaxation measurements showed that the protein backbone and side chains respond to ligand binding by increased conformational fluctuations, on average, that differ among the three ligand-bound states. Variability in the response to ligand binding is prominent in the hydrophobic core, where a distal cluster of methyl groups becomes more rigid, whereas methyl groups closer to the binding site become more flexible. The results reveal an intricate interplay between structure and conformational fluctuations in the different complexes that fine-tunes the affinity. The estimated change in conformational entropy is comparable in magnitude to the binding enthalpy, demonstrating that it contributes favorably and significantly to ligand binding. We speculate that the relatively weak inherent protein-carbohydrate interactions and limited hydrophobic effect associated with oligosaccharide binding might have exerted evolutionary pressure on carbohydrate-binding proteins to increase the affinity by means of conformational entropy.

Enclosed, off-axis solar concentrator

DOEpatents

Benitez, Pablo; Grip, Robert E; Minano, Juan C; Narayanan, Authi A; Plesniak, Adam; Schwartz, Joel A

2013-11-26

A solar concentrator including a housing having receiving wall, a reflecting wall and at least two end walls, the receiving, reflecting and end walls defining a three-dimensional volume having an inlet, wherein a vertical axis of the housing is generally perpendicular to the inlet, a receiver mounted on the receiving wall of the housing, the receiver including at least one photovoltaic cell, wherein a vertical axis of the receiver is disposed at a non-zero angle relative to the vertical axis of the housing, at least one clip disposed on the reflecting wall an optical element received within the three-dimensional volume, the optical element including at least one tab, the tab being engaged by the clip to align the optical element with the receiver, and a window received over the inlet to enclose the housing.

Target dose conformity in 3-dimensional conformal radiotherapy and intensity modulated radiotherapy.

PubMed

Wu, Vincent W C; Kwong, Dora L W; Sham, Jonathan S T

2004-05-01

Dose conformity to the planning target volume is an important criterion in radiotherapy treatment planning, for which the conformity index is a useful assessment tool. The purpose of this study is to compare the differences in CI for the treatment planning of four cancers including the nasopharynx, oesophagus, lung and prostate. Seventy patients with cancers of nasopharynx (30), oesophagus (15), lung (15) and prostate (10) were recruited. Each of these patients was planned with three sets of treatment plans using the FOCUS treatment planning system: the forward and inverse 3DCRT plans and the IMRT plan. The CI was generated for each treatment plan. The mean CI from each cancer patient group was calculated and compared with the other three cancer groups. The mean value of CI was also compared among the three planning methods. The oesophageal and lung cancers demonstrated relatively higher overall mean CI values (0.64 and 0.62, respectively), whereas that of the nasopharynx and prostate were lower (0.54 and 0.50, respectively). With regards to the planning method groups, the IMRT plans produced the highest overall mean CI (0.62), while those for the forward and inverse 3DCRT were similar (0.57 and 0.55, respectively). For the four selected cancers, oesophageal and lung cancers were easier to conform than the nasopharyngeal and prostate cancers. The IMRT plans were more effective in achieving better dose conformity than that of the 3DCRT.

On an algebraic structure of dimensionally reduced magical supergravity theories

NASA Astrophysics Data System (ADS)

Fukuchi, Shin; Mizoguchi, Shun'ya

2018-06-01

We study an algebraic structure of magical supergravities in three dimensions. We show that if the commutation relations among the generators of the quasi-conformal group in the super-Ehlers decomposition are in a particular form, then one can always find a parameterization of the group element in terms of various 3d bosonic fields that reproduces the 3d reduced Lagrangian of the corresponding magical supergravity. This provides a unified treatment of all the magical supergravity theories in finding explicit relations between the 3d dimensionally reduced Lagrangians and particular coset nonlinear sigma models. We also verify that the commutation relations of E 6 (+ 2), the quasi-conformal group for A = C, indeed satisfy this property, allowing the algebraic interpretation of the structure constants and scalar field functions as was done in the F 4 (+ 4) magical supergravity.

Universal bounds on charged states in 2d CFT and 3d gravity

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

Benjamin, Nathan; Dyer, Ethan; Fitzpatrick, A. Liam

2016-08-04

We derive an explicit bound on the dimension of the lightest charged state in two dimensional conformal field theories with a global abelian symmetry. We find that the bound scales with c and provide examples that parametrically saturate this bound. We also prove that any such theory must contain a state with charge-to-mass ratio above a minimal lower bound. As a result, we comment on the implications for charged states in three dimensional theories of gravity.

Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis

PubMed Central

2012-01-01

Background To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. Methods Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). Results In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. Conclusions IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow. PMID:23176540

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy in Japanese patients with locally advanced prostate cancer.

PubMed

Sakamoto, Masato; Mizowaki, Takashi; Mitsumori, Michihide; Takayama, Kenji; Sasai, Keisuke; Norihisa, Yoshiki; Kamoto, Toshiyuki; Nakamura, Eijiro; Ogawa, Osamu; Hiraoka, Masahiro

2010-12-01

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with locally advanced prostate cancer who initiated salvage hormonal therapy (SHT) at a relatively early phase were evaluated. Between April 1998 and April 2003, 70 Japanese patients with T3N0M0 prostate cancer who received radical 3D-CRT treatment were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were 73 years old, 26.3 ng/ml, and 4 months, respectively. Seventy grays were given in 35 fractions that were confined to the prostate and seminal vesicles. Adjuvant hormonal therapy was not administered after 3D-CRT in any of the cases. The median follow-up period was 64.9 months. The median PSA value at the time of initiation of SHT was 5.0 ng/ml (range 0.1-21.6 ng/ml). Overall, disease-specific, PSA failure-free (based on the Phoenix definition) and SHT-free survival rates at 5 years were 90.3% (95% CI 86.5-94.0), 96.5% (94.0-98.9), 60.5% (48.2-72.7), and 63.5% (57.2-69.8), respectively. Therefore, two-thirds of the patients were still hormone-free at 5 years. PSA control rates in our series of Japanese patients with stage T3N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed higher than expected. This approach involving 3D-CRT combined with NAHT with the initiation of SHT at PSA values of around 5 ng/ml may be one option for Japanese patients with locally advanced prostate cancer, although further prospective study is required to confirm the validity.

A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis[reg]) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma

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

Incrocci, Luca; Slagter, Cleo; Slob, A. Koos

2006-10-01

Purpose: Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis (registered) ) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. Methods and Materials: Patients (N = 358) who completed radiotherapy at least 12 months before the study were approached by mail. All patients had been treated by 3DCRT; 60 patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebomore » for 6 weeks. Drug or placebo was taken on demand at patient's discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. At 6 weeks patients crossed over to the alternative treatment. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side effects were also recorded. Results: Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil (placebo: 9%) (p < 0.0001). Side effects were mild or moderate. Conclusions: Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and it is well tolerated.« less

Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost-IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate.

PubMed

Bansal, A; Kapoor, R; Singh, S K; Kumar, N; Oinam, A S; Sharma, S C

2012-07-01

DOSIMETERIC AND RADIOBIOLOGICAL COMPARISON OF TWO RADIATION SCHEDULES IN LOCALIZED CARCINOMA PROSTATE: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT). Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose-volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared. The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively. For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT.

Predictors of High-grade Esophagitis After Definitive Three-dimensional Conformal Therapy, Intensity-modulated Radiation Therapy, or Proton Beam Therapy for Non-small cell Lung Cancer

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

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Tucker, Susan L.; Martel, Mary K.

2012-11-15

Introduction: We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Methods and Materials: Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade {>=}3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Results:more » Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade {>=}3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Conclusions: Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT.« less

Predictors of high-grade esophagitis after definitive three-dimensional conformal therapy, intensity-modulated radiation therapy, or proton beam therapy for non-small cell lung cancer.

PubMed

Gomez, Daniel R; Tucker, Susan L; Martel, Mary K; Mohan, Radhe; Balter, Peter A; Lopez Guerra, Jose Luis; Liu, Hongmei; Komaki, Ritsuko; Cox, James D; Liao, Zhongxing

2012-11-15

We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade≥3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade≥3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT. Copyright © 2012 Elsevier Inc. All rights reserved.

Polyaniline-coated freestanding porous carbon nanofibers as efficient hybrid electrodes for supercapacitors

NASA Astrophysics Data System (ADS)

Tran, Chau; Singhal, Richa; Lawrence, Daniel; Kalra, Vibha

2015-10-01

Three-dimensional, free-standing, hybrid supercapacitor electrodes combining polyaniline (PANI) and porous carbon nanofibers (P-CNFs) were fabricated with the aim to integrate the benefits of both electric double layer capacitors (high power, cyclability) and pseudocapacitors (high energy density). A systematic investigation of three different electropolymerization techniques, namely, potentiodynamic, potentiostatic, and galvanostatic, for electrodeposition of PANI on freestanding carbon nanofiber mats was conducted. It was found that the galvanostatic method, where the current density is kept constant and can be easily controlled facilitates conformal and uniform coating of PANI on three-dimensional carbon nanofiber substrates. The electrochemical tests indicated that the PANI-coated P-CNFs exhibit excellent specific capacitance of 366 F g-1 (vs. 140 F g-1 for uncoated porous carbon nanofibers), 140 F cm-3 volumetric capacitance, and up to 2.3 F cm-2 areal capacitance at 100 mV s-1 scan rate. Such excellent performance is attributed to a thin and conformal coating of PANI achieved using the galvanostatic electrodeposition technique, which not only provides pseudocapacitance with high rate capability, but also retains the double-layer capacitance of the underlying P-CNFs.

Three-dimensional compound comparison methods and their application in drug discovery.

PubMed

Shin, Woong-Hee; Zhu, Xiaolei; Bures, Mark Gregory; Kihara, Daisuke

2015-07-16

Virtual screening has been widely used in the drug discovery process. Ligand-based virtual screening (LBVS) methods compare a library of compounds with a known active ligand. Two notable advantages of LBVS methods are that they do not require structural information of a target receptor and that they are faster than structure-based methods. LBVS methods can be classified based on the complexity of ligand structure information utilized: one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D). Unlike 1D and 2D methods, 3D methods can have enhanced performance since they treat the conformational flexibility of compounds. In this paper, a number of 3D methods will be reviewed. In addition, four representative 3D methods were benchmarked to understand their performance in virtual screening. Specifically, we tested overall performance in key aspects including the ability to find dissimilar active compounds, and computational speed.

Protein secondary structure and stability determined by combining exoproteolysis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Villanueva, Josep; Villegas, Virtudes; Querol, Enrique; Avilés, Francesc X; Serrano, Luis

2002-09-01

In the post-genomic era, several projects focused on the massive experimental resolution of the three-dimensional structures of all the proteins of different organisms have been initiated. Simultaneously, significant progress has been made in the ab initio prediction of protein three-dimensional structure. One of the keys to the success of such a prediction is the use of local information (i.e. secondary structure). Here we describe a new limited proteolysis methodology, based on the use of unspecific exoproteases coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), to map quickly secondary structure elements of a protein from both ends, the N- and C-termini. We show that the proteolytic patterns (mass spectra series) obtained can be interpreted in the light of the conformation and local stability of the analyzed proteins, a direct correlation being observed between the predicted and the experimentally derived protein secondary structure. Further, this methodology can be easily applied to check rapidly the folding state of a protein and characterize mutational effects on protein conformation and stability. Moreover, given global stability information, this methodology allows one to locate the protein regions of increased or decreased conformational stability. All of this can be done with a small fraction of the amount of protein required by most of the other methods for conformational analysis. Thus limited exoproteolysis, together with MALDI-TOF MS, can be a useful tool to achieve quickly the elucidation of protein structure and stability. Copyright 2002 John Wiley & Sons, Ltd.

Mechanisms of Intramolecular Communication in a Hyperthermophilic Acylaminoacyl Peptidase: A Molecular Dynamics Investigation

PubMed Central

Papaleo, Elena; Renzetti, Giulia; Tiberti, Matteo

2012-01-01

Protein dynamics and the underlying networks of intramolecular interactions and communicating residues within the three-dimensional (3D) structure are known to influence protein function and stability, as well as to modulate conformational changes and allostery. Acylaminoacyl peptidase (AAP) subfamily of enzymes belongs to a unique class of serine proteases, the prolyl oligopeptidase (POP) family, which has not been thoroughly investigated yet. POPs have a characteristic multidomain three-dimensional architecture with the active site at the interface of the C-terminal catalytic domain and a β-propeller domain, whose N-terminal region acts as a bridge to the hydrolase domain. In the present contribution, protein dynamics signatures of a hyperthermophilic acylaminoacyl peptidase (AAP) of the prolyl oligopeptidase (POP) family, as well as of a deletion variant and alanine mutants (I12A, V13A, V16A, L19A, I20A) are reported. In particular, we aimed at identifying crucial residues for long range communications to the catalytic site or promoting the conformational changes to switch from closed to open ApAAP conformations. Our investigation shows that the N-terminal α1-helix mediates structural intramolecular communication to the catalytic site, concurring to the maintenance of a proper functional architecture of the catalytic triad. Main determinants of the effects induced by α1-helix are a subset of hydrophobic residues (V16, L19 and I20). Moreover, a subset of residues characterized by relevant interaction networks or coupled motions have been identified, which are likely to modulate the conformational properties at the interdomain interface. PMID:22558199

Heavy-ion conformal irradiation in the shallow-seated tumor therapy terminal at HIRFL.

PubMed

Li, Qiang; Dai, Zhongying; Yan, Zheng; Jin, Xiaodong; Liu, Xinguo; Xiao, Guoqing

2007-11-01

Basic research related to heavy-ion cancer therapy has been done at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Now a plan of clinical trial with heavy ions has been launched at IMP. First, superficially placed tumor treatment with heavy ions is expected in the therapy terminal at the Heavy Ion Research Facility in Lanzhou (HIRFL), where carbon ion beams with energy up to 100 MeV/u can be supplied. The shallow-seated tumor therapy terminal at HIRFL is equipped with a passive beam delivery system including two orthogonal dipole magnets, which continuously scan pencil beams laterally and generate a broad and uniform irradiation field, a motor-driven energy degrader and a multi-leaf collimator. Two different types of range modulator, ripple filter and ridge filter with which Guassian-shaped physical dose and uniform biological effective dose Bragg peaks can be shaped for therapeutic ion beams respectively, have been designed and manufactured. Therefore, two-dimensional and three-dimensional conformal irradiations to tumors can be performed with the passive beam delivery system at the earlier therapy terminal. Both the conformal irradiation methods have been verified experimentally and carbon-ion conformal irradiations to patients with superficially placed tumors have been carried out at HIRFL since November 2006.

Flavor and topological current correlators in parity-invariant three-dimensional QED

NASA Astrophysics Data System (ADS)

Karthik, Nikhil; Narayanan, Rajamani

2017-09-01

We use lattice regularization to study the flow of the flavor-triplet fermion current central charge CJf from its free field value in the ultraviolet limit to its conformal value in the infrared limit of the parity-invariant three-dimensional QED with two flavors of two-component fermions. The dependence of CJf on the scale is weak with a tendency to be below the free field value at intermediate distances. Our numerical data suggest that the flavor-triplet fermion current and the topological current correlators become degenerate within numerical errors in the infrared limit, thereby supporting an enhanced O(4) symmetry predicted by strong self-duality. Further, we demonstrate that fermion dynamics is necessary for the scale-invariant behavior of parity-invariant three-dimensional QED by showing that the pure gauge theory with noncompact gauge action has a nonzero bilinear condensate.

Model based LV-reconstruction in bi-plane x-ray angiography

NASA Astrophysics Data System (ADS)

Backfrieder, Werner; Carpella, Martin; Swoboda, Roland; Steinwender, Clemens; Gabriel, Christian; Leisch, Franz

2005-04-01

Interventional x-ray angiography is state of the art in diagnosis and therapy of severe diseases of the cardiovascular system. Diagnosis is based on contrast enhanced dynamic projection images of the left ventricle. A new model based algorithm for three dimensional reconstruction of the left ventricle from bi-planar angiograms was developed. Parametric super ellipses are deformed until their projection profiles optimally fit measured ventricular projections. Deformation is controlled by a simplex optimization procedure. A resulting optimized parameter set builds the initial guess for neighboring slices. A three dimensional surface model of the ventricle is built from stacked contours. The accuracy of the algorithm has been tested with mathematical phantom data and clinical data. Results show conformance with provided projection data and high convergence speed makes the algorithm useful for clinical application. Fully three dimensional reconstruction of the left ventricle has a high potential for improvements of clinical findings in interventional cardiology.

WIND: Computer program for calculation of three dimensional potential compressible flow about wind turbine rotor blades

NASA Technical Reports Server (NTRS)

Dulikravich, D. S.

1980-01-01

A computer program is presented which numerically solves an exact, full potential equation (FPE) for three dimensional, steady, inviscid flow through an isolated wind turbine rotor. The program automatically generates a three dimensional, boundary conforming grid and iteratively solves the FPE while fully accounting for both the rotating cascade and Coriolis effects. The numerical techniques incorporated involve rotated, type dependent finite differencing, a finite volume method, artificial viscosity in conservative form, and a successive line overrelaxation combined with the sequential grid refinement procedure to accelerate the iterative convergence rate. Consequently, the WIND program is capable of accurately analyzing incompressible and compressible flows, including those that are locally transonic and terminated by weak shocks. The program can also be used to analyze the flow around isolated aircraft propellers and helicopter rotors in hover as long as the total relative Mach number of the oncoming flow is subsonic.

3D fluorescence anisotropy imaging using selective plane illumination microscopy.

PubMed

Hedde, Per Niklas; Ranjit, Suman; Gratton, Enrico

2015-08-24

Fluorescence anisotropy imaging is a popular method to visualize changes in organization and conformation of biomolecules within cells and tissues. In such an experiment, depolarization effects resulting from differences in orientation, proximity and rotational mobility of fluorescently labeled molecules are probed with high spatial resolution. Fluorescence anisotropy is typically imaged using laser scanning and epifluorescence-based approaches. Unfortunately, those techniques are limited in either axial resolution, image acquisition speed, or by photobleaching. In the last decade, however, selective plane illumination microscopy has emerged as the preferred choice for three-dimensional time lapse imaging combining axial sectioning capability with fast, camera-based image acquisition, and minimal light exposure. We demonstrate how selective plane illumination microscopy can be utilized for three-dimensional fluorescence anisotropy imaging of live cells. We further examined the formation of focal adhesions by three-dimensional time lapse anisotropy imaging of CHO-K1 cells expressing an EGFP-paxillin fusion protein.

Three-variable solution in the (2+1)-dimensional null-surface formulation

NASA Astrophysics Data System (ADS)

Harriott, Tina A.; Williams, J. G.

2018-04-01

The null-surface formulation of general relativity (NSF) describes gravity by using families of null surfaces instead of a spacetime metric. Despite the fact that the NSF is (to within a conformal factor) equivalent to general relativity, the equations of the NSF are exceptionally difficult to solve, even in 2+1 dimensions. The present paper gives the first exact (2+1)-dimensional solution that depends nontrivially upon all three of the NSF's intrinsic spacetime variables. The metric derived from this solution is shown to represent a spacetime whose source is a massless scalar field that satisfies the general relativistic wave equation and the Einstein equations with minimal coupling. The spacetime is identified as one of a family of (2+1)-dimensional general relativistic spacetimes discovered by Cavaglià.

A light-trapping strategy for nanocrystalline silicon thin-film solar cells using three-dimensionally assembled nanoparticle structures.

PubMed

Ha, Kyungyeon; Jang, Eunseok; Jang, Segeun; Lee, Jong-Kwon; Jang, Min Seok; Choi, Hoseop; Cho, Jun-Sik; Choi, Mansoo

2016-02-05

We report three-dimensionally assembled nanoparticle structures inducing multiple plasmon resonances for broadband light harvesting in nanocrystalline silicon (nc-Si:H) thin-film solar cells. A three-dimensional multiscale (3DM) assembly of nanoparticles generated using a multi-pin spark discharge method has been accomplished over a large area under atmospheric conditions via ion-assisted aerosol lithography. The multiscale features of the sophisticated 3DM structures exhibit surface plasmon resonances at multiple frequencies, which increase light scattering and absorption efficiency over a wide spectral range from 350-1100 nm. The multiple plasmon resonances, together with the antireflection functionality arising from the conformally deposited top surface of the 3D solar cell, lead to a 22% and an 11% improvement in power conversion efficiency of the nc-Si:H thin-film solar cells compared to flat cells and cells employing nanoparticle clusters, respectively. Finite-difference time-domain simulations were also carried out to confirm that the improved device performance mainly originates from the multiple plasmon resonances generated from three-dimensionally assembled nanoparticle structures.

Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.

PubMed

Ren, Xiao-Cang; Wang, Quan-Yu; Zhang, Rui; Chen, Xue-Ji; Wang, Na; Liu, Yue-E; Zong, Jie; Guo, Zhi-Jun; Wang, Dong-Ying; Lin, Qiang

2016-04-23

Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC. Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied. After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%. For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols. NCT02720614, the date of registration: March 23, 2016.

DFT calculations and NMR measurements applied to the conformational analysis of cis and trans-3-phenylaminocyclohexyl N,N-dimethylcarbamates

NASA Astrophysics Data System (ADS)

Melo, Ulisses Zonta de; Yamazaki, Diego Alberto dos Santos; Cândido, Augusto de Araújo; Basso, Ernani Abicht; Gauze, Gisele de Freitas

2018-07-01

The three-dimensional structure of a potential drug molecule is of critical importance. Factors that determine its conformational stability and, consequently, corresponding biological/physicochemical properties of interest must therefore be carefully analyzed. Conformational properties and molecular structures of cis and trans-3-phenylaminocyclohexyl N,N-dimethylcarbamates were studied by low temperature 1H and 13C NMR spectroscopy and electronic structure calculations. B3LYP and M06-2X methods associated with the 6-311++G(2df,2p) basis set, and the integral-equation-formalism polarizable continuum model were used to study the conformational preferences in dichloromethane, acetone and methanol. NMR measurements indicated that for the cis isomer, the conformer with both substituents in equatorial position is the most stable, while for the trans isomer, the conformer with the carbamate group in the axial position and the arylamine in the equatorial position is favored in all solvents. B3LYP/6-311++G(2df,2p) theory level associated with IEF-PCM described properly the conformational preference in solution. NBO analyses were applied to determine the importance of hyperconjugative interactions in the conformational equilibrium.

Integral radiation dose to normal structures with conformal external beam radiation

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

Aoyama, Hidefumi; Westerly, David Clark; Mackie, Thomas Rockwell

2006-03-01

Background: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. Results: The 6MV-IMRT resulted in 5.0% lower NTID thanmore » 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. Conclusions: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.« less

Evaluating four-loop conformal Feynman integrals by D-dimensional differential equations

NASA Astrophysics Data System (ADS)

Eden, Burkhard; Smirnov, Vladimir A.

2016-10-01

We evaluate a four-loop conformal integral, i.e. an integral over four four-dimensional coordinates, by turning to its dimensionally regularized version and applying differential equations for the set of the corresponding 213 master integrals. To solve these linear differential equations we follow the strategy suggested by Henn and switch to a uniformly transcendental basis of master integrals. We find a solution to these equations up to weight eight in terms of multiple polylogarithms. Further, we present an analytical result for the given four-loop conformal integral considered in four-dimensional space-time in terms of single-valued harmonic polylogarithms. As a by-product, we obtain analytical results for all the other 212 master integrals within dimensional regularization, i.e. considered in D dimensions.

Growth Of High-Cost Intensity-Modulated Radiotherapy For Prostate Cancer Raises Concerns About Overuse

PubMed Central

Jacobs, Bruce L.; Zhang, Yun; Skolarus, Ted A.; Hollenbeck, Brent K.

2012-01-01

To study the impact of new, expensive, and unproven therapies to treat prostate cancer, we investigated the dissemination of intensity-modulated radiotherapy (IMRT). IMRT is an innovative treatment for prostate cancer that delivers higher doses of radiation with improved precision compared to alternative radiotherapies. We observed rapid adoption of this new treatment among men diagnosed with prostate cancer from 2001 through 2007, despite uncertainty about its relative effectiveness. We compared patient and disease characteristics of those receiving IMRT and the previous radiation standard of care, three-dimensional conformal therapy; assessed intermediate-term outcomes; and examined potential factors associated with the increased use of IMRT. We found that in the early period of IMRT adoption (2001–03) men with high-risk disease were more likely to receive IMRT, whereas after IMRT’s initial dissemination (2004–07) men with low-risk disease had fairly similar likelihoods of receiving IMRT as men with high-risk disease. This raises concerns about overtreatment, as well as considerable health care costs, because treatment with IMRT costs $15,000–$20,000 more than other standard therapies. As health care delivery reforms gain traction, policy makers must balance the promotion of new, yet unproven, technology with the risk of overuse. PMID:22492892

Boundary conformal anomalies on hyperbolic spaces and Euclidean balls

NASA Astrophysics Data System (ADS)

Rodriguez-Gomez, Diego; Russo, Jorge G.

2017-12-01

We compute conformal anomalies for conformal field theories with free conformal scalars and massless spin 1/2 fields in hyperbolic space ℍ d and in the ball B^d , for 2≤d≤7. These spaces are related by a conformal transformation. In even dimensional spaces, the conformal anomalies on ℍ2 n and B^{2n} are shown to be identical. In odd dimensional spaces, the conformal anomaly on B^{2n+1} comes from a boundary contribution, which exactly coincides with that of ℍ2 n + 1 provided one identifies the UV short-distance cutoff on B^{2n+1} with the inverse large distance IR cutoff on ℍ2 n + 1, just as prescribed by the conformal map. As an application, we determine, for the first time, the conformal anomaly coefficients multiplying the Euler characteristic of the boundary for scalars and half-spin fields with various boundary conditions in d = 5 and d = 7.

The relative isoperimetric inequality on a conformally parabolic manifold with boundary

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

Kesel'man, Vladimir M

2011-07-31

For an arbitrary noncompact n-dimensional Riemannian manifold with a boundary of conformally parabolic type it is proved that there exists a conformal change of metric such that a relative isoperimetric inequality of the same form as in the closed n-dimensional Euclidean half-space holds on the manifold with the new metric. This isoperimetric inequality is asymptotically sharp. Bibliography: 6 titles.

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism.

PubMed

Vollmeyer, Joscha; Eberhagen, Friederike; Höger, Sigurd; Jester, Stefan-S

2014-01-01

Three shape-persistent naphthylene-phenylene-acetylene macrocycles of identical backbone structures and extraannular substitution patterns but different (empty, apolar, polar) nanopore fillings are self-assembled at the solid/liquid interface of highly oriented pyrolytic graphite and 1,2,4-trichlorobenzene. Submolecularly resolved images of the resulting two-dimensional (2D) crystalline monolayer patterns are obtained by in situ scanning tunneling microscopy. A concentration-dependent conformational polymorphism is found, and open and more dense packing motifs are observed. For all three compounds alike lattice parameters are found, therefore the intermolecular macrocycle distances are mainly determined by their size and symmetry. This is an excellent example that the graphite acts as a template for the macrocycle organization independent from their specific interior.

Assigned and unassigned distance geometry: applications to biological molecules and nanostructures

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

Billinge, Simon J. L.; Duxbury, Phillip M.; Gonçalves, Douglas S.

2016-04-04

Here, considering geometry based on the concept of distance, the results found by Menger and Blumenthal originated a body of knowledge called distance geometry. This survey covers some recent developments for assigned and unassigned distance geometry and focuses on two main applications: determination of three-dimensional conformations of biological molecules and nanostructures.

Reconstructing spatial organizations of chromosomes through manifold learning

PubMed Central

Deng, Wenxuan; Hu, Hailin; Ma, Rui; Zhang, Sai; Yang, Jinglin; Peng, Jian; Kaplan, Tommy; Zeng, Jianyang

2018-01-01

Abstract Decoding the spatial organizations of chromosomes has crucial implications for studying eukaryotic gene regulation. Recently, chromosomal conformation capture based technologies, such as Hi-C, have been widely used to uncover the interaction frequencies of genomic loci in a high-throughput and genome-wide manner and provide new insights into the folding of three-dimensional (3D) genome structure. In this paper, we develop a novel manifold learning based framework, called GEM (Genomic organization reconstructor based on conformational Energy and Manifold learning), to reconstruct the three-dimensional organizations of chromosomes by integrating Hi-C data with biophysical feasibility. Unlike previous methods, which explicitly assume specific relationships between Hi-C interaction frequencies and spatial distances, our model directly embeds the neighboring affinities from Hi-C space into 3D Euclidean space. Extensive validations demonstrated that GEM not only greatly outperformed other state-of-art modeling methods but also provided a physically and physiologically valid 3D representations of the organizations of chromosomes. Furthermore, we for the first time apply the modeled chromatin structures to recover long-range genomic interactions missing from original Hi-C data. PMID:29408992

The construction of ``realistic'' four-dimensional strings through orbifolds

NASA Astrophysics Data System (ADS)

Font, A.; Ibáñez, L. E.; Quevedo, F.; Sierra, A.

1990-02-01

We discuss the construction of "realistic" lower rank 4-dimensional strings, through symmetric orbifolds with background fields. We present Z 3 three-generation SU(3) × SU(2) × U(1) models as well as models incorporating a left-right SU(2) L × SU(2) R × U(1) B-L symmetry in which proton stability is automatically guaranteed. Conformal field theory selection rules are used to find the flat directions to all orders which lead to these low-rank models and to study the relevant Yukawa couplings. A hierarchical structure of quark-lepton masses appears naturally in some models. We also present a detailed study of the structure of the Z 3 × Z 3 orbifold including the generalized GSO projection, the effect of discrete torsion and the conformal field theory Yukawa coupling selection rules. All these points are illustrated with a three-generation Z 3 × Z 3 model. We have made an effort to write a self-contained presentation in order to make this material available to non-string experts interested in the phenomenological aspects of this theory.

Reconstructing spatial organizations of chromosomes through manifold learning.

PubMed

Zhu, Guangxiang; Deng, Wenxuan; Hu, Hailin; Ma, Rui; Zhang, Sai; Yang, Jinglin; Peng, Jian; Kaplan, Tommy; Zeng, Jianyang

2018-05-04

Decoding the spatial organizations of chromosomes has crucial implications for studying eukaryotic gene regulation. Recently, chromosomal conformation capture based technologies, such as Hi-C, have been widely used to uncover the interaction frequencies of genomic loci in a high-throughput and genome-wide manner and provide new insights into the folding of three-dimensional (3D) genome structure. In this paper, we develop a novel manifold learning based framework, called GEM (Genomic organization reconstructor based on conformational Energy and Manifold learning), to reconstruct the three-dimensional organizations of chromosomes by integrating Hi-C data with biophysical feasibility. Unlike previous methods, which explicitly assume specific relationships between Hi-C interaction frequencies and spatial distances, our model directly embeds the neighboring affinities from Hi-C space into 3D Euclidean space. Extensive validations demonstrated that GEM not only greatly outperformed other state-of-art modeling methods but also provided a physically and physiologically valid 3D representations of the organizations of chromosomes. Furthermore, we for the first time apply the modeled chromatin structures to recover long-range genomic interactions missing from original Hi-C data.

Comprehensive analysis of the dynamic structure of nuclear localization signals.

PubMed

Yamagishi, Ryosuke; Okuyama, Takahide; Oba, Shuntaro; Shimada, Jiro; Chaen, Shigeru; Kaneko, Hiroki

2015-12-01

Most transcription and epigenetic factors in eukaryotic cells have nuclear localization signals (NLSs) and are transported to the nucleus by nuclear transport proteins. Understanding the features of NLSs and the mechanisms of nuclear transport might help understand gene expression regulation, somatic cell reprogramming, thus leading to the treatment of diseases associated with abnormal gene expression. Although many studies analyzed the amino acid sequence of NLSs, few studies investigated their three-dimensional structure. Therefore, we conducted a statistical investigation of the dynamic structure of NLSs by extracting the conformation of these sequences from proteins examined by X-ray crystallography and using a quantity defined as conformational determination rate (a ratio between the number of amino acids determining the conformation and the number of all amino acids included in a certain region). We found that determining the conformation of NLSs is more difficult than determining the conformation of other regions and that NLSs may tend to form more heteropolymers than monomers. Therefore, these findings strongly suggest that NLSs are intrinsically disordered regions.

AdS 2 holographic dictionary

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

Cvetic, Mirjam; Papadimitriou, Ioannis

Here, we construct the holographic dictionary for both running and constant dilaton solutions of the two dimensional Einstein-Maxwell-Dilaton theory that is obtained by a circle reduction from Einstein-Hilbert gravity with negative cosmological constant in three dimensions. This specific model ensures that the dual theory has a well defined ultraviolet completion in terms of a two dimensional conformal field theory, but our results apply qualitatively to a wider class of two dimensional dilaton gravity theories. For each type of solutions we perform holographic renormalization, compute the exact renormalized one-point functions in the presence of arbitrary sources, and derive the asymptotic symmetriesmore » and the corresponding conserved charges. In both cases we find that the scalar operator dual to the dilaton plays a crucial role in the description of the dynamics. Its source gives rise to a matter conformal anomaly for the running dilaton solutions, while its expectation value is the only non trivial observable for constant dilaton solutions. The role of this operator has been largely overlooked in the literature. We further show that the only non trivial conserved charges for running dilaton solutions are the mass and the electric charge, while for constant dilaton solutions only the electric charge is non zero. However, by uplifting the solutions to three dimensions we show that constant dilaton solutions can support non trivial extended symmetry algebras, including the one found by Compère, Song and Strominger, in agreement with the results of Castro and Song. Finally, we demonstrate that any solution of this specific dilaton gravity model can be uplifted to a family of asymptotically AdS 2 × S 2 or conformally AdS 2 × S 2 solutions of the STU model in four dimensions, including non extremal black holes. As a result, the four dimensional solutions obtained by uplifting the running dilaton solutions coincide with the so called ‘subtracted geometries’, while those obtained from the uplift of the constant dilaton ones are new.« less

AdS 2 holographic dictionary

DOE PAGES

Cvetic, Mirjam; Papadimitriou, Ioannis

2016-12-02

Here, we construct the holographic dictionary for both running and constant dilaton solutions of the two dimensional Einstein-Maxwell-Dilaton theory that is obtained by a circle reduction from Einstein-Hilbert gravity with negative cosmological constant in three dimensions. This specific model ensures that the dual theory has a well defined ultraviolet completion in terms of a two dimensional conformal field theory, but our results apply qualitatively to a wider class of two dimensional dilaton gravity theories. For each type of solutions we perform holographic renormalization, compute the exact renormalized one-point functions in the presence of arbitrary sources, and derive the asymptotic symmetriesmore » and the corresponding conserved charges. In both cases we find that the scalar operator dual to the dilaton plays a crucial role in the description of the dynamics. Its source gives rise to a matter conformal anomaly for the running dilaton solutions, while its expectation value is the only non trivial observable for constant dilaton solutions. The role of this operator has been largely overlooked in the literature. We further show that the only non trivial conserved charges for running dilaton solutions are the mass and the electric charge, while for constant dilaton solutions only the electric charge is non zero. However, by uplifting the solutions to three dimensions we show that constant dilaton solutions can support non trivial extended symmetry algebras, including the one found by Compère, Song and Strominger, in agreement with the results of Castro and Song. Finally, we demonstrate that any solution of this specific dilaton gravity model can be uplifted to a family of asymptotically AdS 2 × S 2 or conformally AdS 2 × S 2 solutions of the STU model in four dimensions, including non extremal black holes. As a result, the four dimensional solutions obtained by uplifting the running dilaton solutions coincide with the so called ‘subtracted geometries’, while those obtained from the uplift of the constant dilaton ones are new.« less

Quantum deformations of conformal algebras with mass-like deformation parameters

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

Frydryszak, Andrzej; Lukierski, Jerzy; Mozrzymas, Marek

1998-12-15

We recall the mathematical apparatus necessary for the quantum deformation of Lie algebras, namely the notions of coboundary Lie algebras, classical r-matrices, classical Yang-Baxter equations (CYBE), Froebenius algebras and parabolic subalgebras. Then we construct the quantum deformation of D=1, D=2 and D=3 conformal algebras, showing that this quantization introduce fundamental mass parameters. Finally we consider with more details the quantization of D=4 conformal algebra. We build three classes of sl(4,C) classical r-matrices, satisfying CYBE and depending respectively on 8, 10 and 12 generators of parabolic subalgebras. We show that only the 8-dimensional r-matrices allow to impose the D=4 conformal o(4,2){approx_equal}su(2,2)more » reality conditions. Weyl reflections and Dynkin diagram automorphisms for o(4,2) define the class of admissible bases for given classical r-matrices.« less

Microsecond protein dynamics observed at the single-molecule level

NASA Astrophysics Data System (ADS)

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-07-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape.

Microsecond protein dynamics observed at the single-molecule level

PubMed Central

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-01-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape. PMID:26151767

Manipulation of Origin of Life Molecules: Recognizing Single-Molecule Conformations in β-Carotene and Chlorophyll-a/β-Carotene Clusters

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

Ngo, Anh T.; Skeini, Timur; Iancu, Violeta

Carotenoids and chlorophyll are essential parts of plant leaves and are involved in photosynthesis, a vital biological process responsible for the origin of life on Earth. Here, we investigate how beta-carotene and chlorophyll-a form mixed molecular phases On a Au(111) surface using low-temperature scanning tunneling microscopy and molecular manipulation at the single-molecule level supported by density functional theory calculations. By isolating individual molecules from nanoscale molecular clusters with a scanning tunneling microscope tip, we are able to identify five beta-carotene conformations including a structure exhibiting a three-dimensional conformation. Furthermore, molecular resolution images enable direct visualization of beta-carotene/chlorophyll-a clsuters, with intimatemore » structural details highlighting how they pair: beta-carotene preferentially positions next to chlorophyll-a and induces switching of chlorophyll-a from straight to several bent tail conformations in the molecular clusters.« less

CT-based definition of thoracic lymph node stations: an atlas from the University of Michigan.

PubMed

Chapet, Olivier; Kong, Feng-Ming; Quint, Leslie E; Chang, Andrew C; Ten Haken, Randall K; Eisbruch, Avraham; Hayman, James A

2005-09-01

Accurate delineation of the mediastinal and hilar lymph node regions is essential for a reproducible definition of target volumes used in conformal irradiation of non-small-cell lung cancer. The goal of this work was to generate a consensus to delineate these nodal regions based on definitions from the American Joint Committee on Cancer. A dedicated thoracic radiologist, thoracic surgeon, medical physicist, and three radiation oncologists were gathered to generate a three-dimensional radiologic description for the mediastinal and hilar nodal regions on axial CT scans. This paper proposes an atlas of most of the lymph node stations described by Mountain and Dresler. The CT boundaries of lymph node stations 1-2, 3, 4, 5, 6, 7, 8, 10-11 were defined on axial CT, along with image illustrations. These CT-based illustrative definitions will provide guidelines for clinical practice and studies evaluating incidental radiation in radiotherapy. Studies are ongoing at the University of Michigan to measure quantitatively the incidental nodal radiation received by patients with non-small-cell lung cancer.

Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

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

Oliveira Lopes, Carlos; Callera, Fernando, E-mail: fcallera@gmail.com

Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrastmore » with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.« less

The solution structures of the cucumber mosaic virus and tomato aspermy virus coat proteins explored with molecular dynamics simulations.

PubMed

Gellért, Akos; Balázs, Ervin

2010-02-26

The three-dimensional structures of two cucumovirus coat proteins (CP), namely Cucumber mosaic virus (CMV) and Tomato aspermy virus (TAV), were explored by molecular dynamics (MD) simulations. The N-terminal domain and the C-terminal tail of the CPs proved to be intrinsically unstructured protein regions in aqueous solution. The N-terminal alpha-helix had a partially unrolled conformation. The thermal factor analysis of the CP loop regions demonstrated that the CMV CP had more flexible loop regions than the TAV CP. The principal component analysis (PCA) of the MD trajectories showed that the first three eigenvectors represented the three main conformational motions in the CPs. The first motion components with the highest variance contribution described an opening movement between the hinge and the N-terminal domain of both CPs. The second eigenvector showed a closing motion, while the third eigenvector represented crosswise conformational fluctuations. These new findings, together with previous results, suggest that the hinge region of CPs plays a central role in the recognition and binding of viral RNA. Copyright 2009 Elsevier Inc. All rights reserved.

Generative Topographic Mapping of Conformational Space.

PubMed

Horvath, Dragos; Baskin, Igor; Marcou, Gilles; Varnek, Alexandre

2017-10-01

Herein, Generative Topographic Mapping (GTM) was challenged to produce planar projections of the high-dimensional conformational space of complex molecules (the 1LE1 peptide). GTM is a probability-based mapping strategy, and its capacity to support property prediction models serves to objectively assess map quality (in terms of regression statistics). The properties to predict were total, non-bonded and contact energies, surface area and fingerprint darkness. Map building and selection was controlled by a previously introduced evolutionary strategy allowed to choose the best-suited conformational descriptors, options including classical terms and novel atom-centric autocorrellograms. The latter condensate interatomic distance patterns into descriptors of rather low dimensionality, yet precise enough to differentiate between close favorable contacts and atom clashes. A subset of 20 K conformers of the 1LE1 peptide, randomly selected from a pool of 2 M geometries (generated by the S4MPLE tool) was employed for map building and cross-validation of property regression models. The GTM build-up challenge reached robust three-fold cross-validated determination coefficients of Q 2 =0.7…0.8, for all modeled properties. Mapping of the full 2 M conformer set produced intuitive and information-rich property landscapes. Functional and folding subspaces appear as well-separated zones, even though RMSD with respect to the PDB structure was never used as a selection criterion of the maps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predicting the conformations of peptides and proteins in early evolution. A review article submitted to Biology Direct

PubMed Central

Milner-White, E James; Russell, Michael J

2008-01-01

Considering that short, mainly heterochiral, polypeptides with a high glycine content are expected to have played a prominent role in evolution at the earliest stage of life before nucleic acids were available, we review recent knowledge about polypeptide three-dimensional structure to predict the types of conformations they would have adopted. The possible existence of such structures at this time leads to a consideration of their functional significance, and the consequences for the course of evolution. This article was reviewed by Bill Martin, Eugene Koonin and Nick Grishin. PMID:18226248

9-(3,4-Dimeth­oxy­phen­yl)-3,4,5,6,7,9-hexa­hydroxanthene-1,8(2H)-dione

PubMed Central

Mehdi, Sayed Hasan; Hashim, Rokiah; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-01-01

In the title compound, C21H22O5, the mean planes of the pyran and dimeth­oxy­phenyl rings are nearly perpendicular to one another, with the dihedral angle between them being 88.21 (8)°. The pyran ring adopts a boat conformation whereas the two fused cyclo­hexane rings adopt envelope conformations. In the crystal, mol­ecules are linked into a three-dimensional network by inter­molecular C—H⋯O hydrogen bonds. PMID:21754824

Multiple two-dimensional versus three-dimensional PTV definition in treatment planning for conformal radiotherapy.

PubMed

Stroom, J C; Korevaar, G A; Koper, P C; Visser, A G; Heijmen, B J

1998-06-01

To demonstrate the need for a fully three-dimensional (3D) computerized expansion of the gross tumour volume (GTV) or clinical target volume (CTV), as delineated by the radiation oncologist on CT slices, to obtain the proper planning target volume (PTV) for treatment planning according to the ICRU-50 recommendations. For 10 prostate cancer patients two PTVs have been determined by expansion of the GTV with a 1.5 cm margin, i.e. a 3D PTV and a multiple 2D PTV. The former was obtained by automatically adding the margin while accounting in 3D for GTV contour differences in neighbouring slices. The latter was generated by automatically adding the 1.5 cm margin to the GTV in each CT slice separately; the resulting PTV is a computer simulation of the PTV that a radiation oncologist would obtain with (the still common) manual contouring in CT slices. For each patient the two PTVs were compared to assess the deviations of the multiple 2D PTV from the 3D PTV. For both PTVs conformal plans were designed using a three-field technique with fixed block margins. For each patient dose-volume histograms and tumour control probabilities (TCPs) of the (correct) 3D PTV were calculated, both for the plan designed for this PTV and for the treatment plan based on the (deviating) 2D PTV. Depending on the shape of the GTV, multiple 2D PTV generation could locally result in a 1 cm underestimation of the GTV-to-PTV margin. The deviations occurred predominantly in the cranio-caudal direction at locations where the GTV contour shape varies significantly from slice to slice. This could lead to serious underdosage and to a TCP decrease of up to 15%. A full 3D GTV-to-PTV expansion should be applied in conformal radiotherapy to avoid underdosage.

Control theory based airfoil design for potential flow and a finite volume discretization

NASA Technical Reports Server (NTRS)

Reuther, J.; Jameson, A.

1994-01-01

This paper describes the implementation of optimization techniques based on control theory for airfoil design. In previous studies it was shown that control theory could be used to devise an effective optimization procedure for two-dimensional profiles in which the shape is determined by a conformal transformation from a unit circle, and the control is the mapping function. The goal of our present work is to develop a method which does not depend on conformal mapping, so that it can be extended to treat three-dimensional problems. Therefore, we have developed a method which can address arbitrary geometric shapes through the use of a finite volume method to discretize the potential flow equation. Here the control law serves to provide computationally inexpensive gradient information to a standard numerical optimization method. Results are presented, where both target speed distributions and minimum drag are used as objective functions.

Hidden Markov model-derived structural alphabet for proteins: the learning of protein local shapes captures sequence specificity.

PubMed

Camproux, A C; Tufféry, P

2005-08-05

Understanding and predicting protein structures depend on the complexity and the accuracy of the models used to represent them. We have recently set up a Hidden Markov Model to optimally compress protein three-dimensional conformations into a one-dimensional series of letters of a structural alphabet. Such a model learns simultaneously the shape of representative structural letters describing the local conformation and the logic of their connections, i.e. the transition matrix between the letters. Here, we move one step further and report some evidence that such a model of protein local architecture also captures some accurate amino acid features. All the letters have specific and distinct amino acid distributions. Moreover, we show that words of amino acids can have significant propensities for some letters. Perspectives point towards the prediction of the series of letters describing the structure of a protein from its amino acid sequence.

Förster resonance energy transfer and protein-induced fluorescence enhancement as synergetic multi-scale molecular rulers

NASA Astrophysics Data System (ADS)

Ploetz, Evelyn; Lerner, Eitan; Husada, Florence; Roelfs, Martin; Chung, Sangyoon; Hohlbein, Johannes; Weiss, Shimon; Cordes, Thorben

2016-09-01

Advanced microscopy methods allow obtaining information on (dynamic) conformational changes in biomolecules via measuring a single molecular distance in the structure. It is, however, extremely challenging to capture the full depth of a three-dimensional biochemical state, binding-related structural changes or conformational cross-talk in multi-protein complexes using one-dimensional assays. In this paper we address this fundamental problem by extending the standard molecular ruler based on Förster resonance energy transfer (FRET) into a two-dimensional assay via its combination with protein-induced fluorescence enhancement (PIFE). We show that donor brightness (via PIFE) and energy transfer efficiency (via FRET) can simultaneously report on e.g., the conformational state of double stranded DNA (dsDNA) following its interaction with unlabelled proteins (BamHI, EcoRV, and T7 DNA polymerase gp5/trx). The PIFE-FRET assay uses established labelling protocols and single molecule fluorescence detection schemes (alternating-laser excitation, ALEX). Besides quantitative studies of PIFE and FRET ruler characteristics, we outline possible applications of ALEX-based PIFE-FRET for single-molecule studies with diffusing and immobilized molecules. Finally, we study transcription initiation and scrunching of E. coli RNA-polymerase with PIFE-FRET and provide direct evidence for the physical presence and vicinity of the polymerase that causes structural changes and scrunching of the transcriptional DNA bubble.

Förster resonance energy transfer and protein-induced fluorescence enhancement as synergetic multi-scale molecular rulers

PubMed Central

Ploetz, Evelyn; Lerner, Eitan; Husada, Florence; Roelfs, Martin; Chung, SangYoon; Hohlbein, Johannes; Weiss, Shimon; Cordes, Thorben

2016-01-01

Advanced microscopy methods allow obtaining information on (dynamic) conformational changes in biomolecules via measuring a single molecular distance in the structure. It is, however, extremely challenging to capture the full depth of a three-dimensional biochemical state, binding-related structural changes or conformational cross-talk in multi-protein complexes using one-dimensional assays. In this paper we address this fundamental problem by extending the standard molecular ruler based on Förster resonance energy transfer (FRET) into a two-dimensional assay via its combination with protein-induced fluorescence enhancement (PIFE). We show that donor brightness (via PIFE) and energy transfer efficiency (via FRET) can simultaneously report on e.g., the conformational state of double stranded DNA (dsDNA) following its interaction with unlabelled proteins (BamHI, EcoRV, and T7 DNA polymerase gp5/trx). The PIFE-FRET assay uses established labelling protocols and single molecule fluorescence detection schemes (alternating-laser excitation, ALEX). Besides quantitative studies of PIFE and FRET ruler characteristics, we outline possible applications of ALEX-based PIFE-FRET for single-molecule studies with diffusing and immobilized molecules. Finally, we study transcription initiation and scrunching of E. coli RNA-polymerase with PIFE-FRET and provide direct evidence for the physical presence and vicinity of the polymerase that causes structural changes and scrunching of the transcriptional DNA bubble. PMID:27641327

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Singh, Anurag K; Lockett, Mary Ann; Bradley, Jeffrey D

2003-02-01

To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

A conformal transceive array for 7 T neuroimaging.

PubMed

Gilbert, Kyle M; Belliveau, Jean-Guy; Curtis, Andrew T; Gati, Joseph S; Klassen, L Martyn; Menon, Ravi S

2012-05-01

The first 16-channel transceive surface-coil array that conforms to the human head and operates at 298 MHz (7 T) is described. Individual coil elements were decoupled using circumferential shields around each element that extended orthogonally from the former. This decoupling method allowed elements to be constructed with arbitrary shape, size, and location to create a three-dimensional array. Radiofrequency shimming achieved a transmit-field uniformity of 20% over the whole brain and 14% over a single axial slice. During radiofrequency transmission, coil elements couple tightly to the head and reduce the amount of power necessary to achieve a mean 90° flip angle (660-μs and 480-μs pulse lengths were required for a 1-kW hard pulse when shimming over the whole brain and a single axial slice, respectively). During reception, the close proximity of coil elements to the head increases the signal-to-noise ratio in the periphery of the brain, most notably at the superior aspect of the head. The sensitivity profile of each element is localized beneath the respective shield. When combined with the achieved isolation between elements, this results in the capacity for low geometry factors during both transmit and receive: 1.04/1.06 (mean) and 1.25/1.54 (maximum) for 3-by-3 acceleration in the axial/sagittal plane. High cortical signal-to-noise ratio and parallel imaging performance make the conformal coil ideal for the study of high temporal and/or spatial cortical architecture and function. Copyright © 2011 Wiley Periodicals, Inc.

Hypothyroidism After Radiotherapy for Nasopharyngeal Cancer Patients

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

Wu, Y.-H.; Wang, H-M.; Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Purpose: The aim of this study was to determine the long-term incidence and possible predictive factors for posttreatment hypothyroidism in nasopharyngeal carcinoma (NPC) patients after radiotherapy. Methods and Materials: Four hundred and eight sequential NPC patients who had received regular annual thyroid hormone surveys prospectively after radiotherapy were included in this study. Median patient age was 47.3 years, and 286 patients were male. Thyroid function was prospectively evaluated by measuring thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) levels. Low FT4 levels indicated clinical hypothyroidism in this study. Results: With a median follow-up of 4.3 years (range, 0.54-19.7 years), themore » incidence of low FT4 level was 5.3%, 9.0%, and 19.1% at 3, 5, and 10 years after radiotherapy, respectively. Hypothyroidism was more common with early T stage (p = 0.044), female sex (p = 0.037), and three-dimensional conformal therapy with the altered fractionation technique (p = 0.005) after univariate analysis. N stage, chemotherapy, reirradiation, and neck electron boost did not affect the incidence of hypothyroidism. Younger age and conformal therapy were significant factors that determined clinical hypothyroidism after multivariate analysis. Overall, patients presented with a low FT4 level about 1 year after presenting with an elevated TSH level. Conclusion: Among our study group of NPC patients, 19.1% experienced clinical hypothyroidism by 10 years after treatment. Younger age and conformal therapy increased the risk of hypothyroidism. We suggest routine evaluation of thyroid function in NPC patients after radiotherapy. The impact of pituitary injury should be also considered.« less

Evaluations of the conformational search accuracy of CAMDAS using experimental three-dimensional structures of protein-ligand complexes

NASA Astrophysics Data System (ADS)

Oda, A.; Yamaotsu, N.; Hirono, S.; Takano, Y.; Fukuyoshi, S.; Nakagaki, R.; Takahashi, O.

2013-08-01

CAMDAS is a conformational search program, through which high temperature molecular dynamics (MD) calculations are carried out. In this study, the conformational search ability of CAMDAS was evaluated using structurally known 281 protein-ligand complexes as a test set. For the test, the influences of initial settings and initial conformations on search results were validated. By using the CAMDAS program, reasonable conformations whose root mean square deviations (RMSDs) in comparison with crystal structures were less than 2.0 Å could be obtained from 96% of the test set even though the worst initial settings were used. The success rate was comparable to those of OMEGA, and the errors of CAMDAS were less than those of OMEGA. Based on the results obtained using CAMDAS, the worst RMSD was around 2.5 Å, although the worst value obtained was around 4.0 Å using OMEGA. The results indicated that CAMDAS is a robust and versatile conformational search method and that it can be used for a wide variety of small molecules. In addition, the accuracy of a conformational search in relation to this study was improved by longer MD calculations and multiple MD simulations.

New insights into the folding of a β-sheet miniprotein in a reduced space of collective hydrogen bond variables: application to a hydrodynamic analysis of the folding flow.

PubMed

Kalgin, Igor V; Caflisch, Amedeo; Chekmarev, Sergei F; Karplus, Martin

2013-05-23

A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed, and it is complemented by a hydrodynamic analysis. The latter, making use of "passive tracers" in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance in the hydrogen bond subspace. Comparison with the many published studies shows good agreement with the present analysis for the parts that can be compared, supporting the robust character of our understanding of this "hydrogen atom" of protein folding.

Three-dimensional control of crystal growth using magnetic fields

NASA Astrophysics Data System (ADS)

Dulikravich, George S.; Ahuja, Vineet; Lee, Seungsoo

1993-07-01

Two coupled systems of partial differential equations governing three-dimensional laminar viscous flow undergoing solidification or melting under the influence of arbitrarily oriented externally applied magnetic fields have been formulated. The model accounts for arbitrary temperature dependence of physical properties including latent heat release, effects of Joule heating, magnetic field forces, and mushy region existence. On the basis of this model a numerical algorithm has been developed and implemented using central differencing on a curvilinear boundary-conforming grid and Runge-Kutta explicit time-stepping. The numerical results clearly demonstrate possibilities for active and practically instantaneous control of melt/solid interface shape, the solidification/melting front propagation speed, and the amount and location of solid accrued.

Consistency condition for inflation from (broken) conformal symmetry

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

Schalm, Koenraad; Aalst, Ted van der; Shiu, Gary, E-mail: kschalm@lorentz.leidenuniv.nl, E-mail: shiu@physics.wisc.edu, E-mail: vdaalst@lorentz.leidenuniv.nl

2013-03-01

We investigate the symmetry constraints on the bispectrum, i.e. the three-point correlation function of primordial density fluctuations, in slow-roll inflation. It follows from the defining property of slow-roll inflation that primordial correlation functions inherit most of their structure from weakly broken de Sitter symmetries. Using holographic techniques borrowed from the AdS/CFT correspondence, the symmetry constraints on the bispectrum can be mapped to a set of stress-tensor Ward identities in a weakly broken 2+1-dimensional Euclidean CFT. We construct the consistency condition from these Ward identities using conformal perturbation theory. This requires a second order Ward identity and the use of themore » evolution equation. Our result also illustrates a subtle difference between conformal perturbation theory and the slow-roll expansion.« less

On some 3-point functions in the W 4 CFT and related braiding matrix

NASA Astrophysics Data System (ADS)

Furlan, P.; Petkova, V. B.

2015-12-01

We construct a class of 3-point constants in the sl(4) Toda conformal theory W 4, extending the examples in Fateev and Litvinov [1]. Their knowledge allows to determine the braiding/fusing matrix transforming 4-point conformal blocks of one fundamental, labelled by the 6-dimensional sl(4) representation, and three partially degenerate vertex operators. It is a 3 × 3 submatrix of the generic 6 × 6 fusing matrix consistent with the fusion rules for the particular class of representations. We check a braiding relation which has wider applications to conformal models with sl(4) symmetry. The 3-point constants in dual regions of central charge are compared in preparation for a BPS like relation in the widehat{sl}(4) WZW model.

Crystal structure of an Okazaki fragment at 2-A resolution

NASA Technical Reports Server (NTRS)

Egli, M.; Usman, N.; Zhang, S. G.; Rich, A.

1992-01-01

In DNA replication, Okazaki fragments are formed as double-stranded intermediates during synthesis of the lagging strand. They are composed of the growing DNA strand primed by RNA and the template strand. The DNA oligonucleotide d(GGGTATACGC) and the chimeric RNA-DNA oligonucleotide r(GCG)d(TATACCC) were combined to form a synthetic Okazaki fragment and its three-dimensional structure was determined by x-ray crystallography. The fragment adopts an overall A-type conformation with 11 residues per turn. Although the base-pair geometry, particularly in the central TATA part, is distorted, there is no evidence for a transition from the A- to the B-type conformation at the junction between RNA.DNA hybrid and DNA duplex. The RNA trimer may, therefore, lock the complete fragment in an A-type conformation.

Radiation dose-volume effects in the esophagus.

PubMed

Werner-Wasik, Maria; Yorke, Ellen; Deasy, Joseph; Nam, Jiho; Marks, Lawrence B

2010-03-01

Publications relating esophageal radiation toxicity to clinical variables and to quantitative dose and dose-volume measures derived from three-dimensional conformal radiotherapy for non-small-cell lung cancer are reviewed. A variety of clinical and dosimetric parameters have been associated with acute and late toxicity. Suggestions for future studies are presented. Copyright 2010 Elsevier Inc. All rights reserved.

Agonists and antagonists for P2 receptors

PubMed Central

Jacobson, Kenneth A.; Costanzi, Stefano; Joshi, Bhalchandra V.; Besada, Pedro; Shin, Dae Hong; Ko, Hyojin; Ivanov, Andrei A.; Mamedova, Liaman

2015-01-01

Recent work has identified nucleotide agonists selective for P2Y1, P2Y2 and P2Y6 receptors and nucleotide antagonists selective for P2Y1, P2Y12 and P2X1 receptors. Selective non-nucleotide antagonists have been reported for P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, P2X2/3/P2X3 and P2X7 receptors. For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non-nucleotide antagonist A-317491 is selective for P2X2/3/P2X3 receptors. Nucleotide analogues in which the ribose moiety is substituted by a variety of novel ring systems, including conformation-ally locked moieties, have been synthesized as ligands for P2Y receptors. The focus on conformational factors of the ribose-like moiety allows the inclusion of general modifications that lead to enhanced potency and selectivity. At P2Y1,2,4,11 receptors, there is a preference for the North conformation as indicated with (N)-methanocarba analogues. The P2Y1 antagonist MRS2500 inhibited ADP-induced human platelet aggregation with an IC50 of 0.95 nM. MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency (EC50) of 0.4 nM at the P2Y1 receptor, with >10 000-fold selectivity in comparison to P2Y12 and P2Y13 receptors. At P2Y6 receptors there is a dramatic preference for the South conformation. Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three-dimensional structures of P2X receptors have not yet been proposed. PMID:16805423

Conformity, Anticonformity, andIndependence: Their Dimensionality and Generality

ERIC Educational Resources Information Center

Stricker, Lawrence J.; And Others

1970-01-01

Examines response to group pressure involving different judgments and social situations. One bipolar dimension included conformity and anticonformity, the other, conformity and independence. Tables, graphs, and bibliography. (RW)

Application of two-dimensional NMR spectroscopy and molecular dynamics simulations to the conformational analysis of oligosaccharides corresponding to the cell-wall polysaccharide of Streptococcus group A.

PubMed

Kreis, U C; Varma, V; Pinto, B M

1995-06-01

This paper describes the use of a protocol for conformational analysis of oligosaccharide structures related to the cell-wall polysaccharide of Streptococcus group A. The polysaccharide features a branched structure with an L-rhamnopyranose (Rhap) backbone consisting of alternating alpha-(1-->2) and alpha-(1-->3) links and D-N-acetylglucosamine (GlcpNAc) residues beta-(1-->3)-connected to alternating rhamnose rings: [formula: see text] Oligomers consisting of three to six residues have been synthesized and nuclear magnetic resonance (NMR) assignments have been made. The protocol for conformational analysis of the solution structure of these oligosaccharides involves experimental and theoretical methods. Two-dimensional NMR spectroscopy methods (TOCSY, ROESY and NOESY) are utilized to obtain chemical shift data and proton-proton distances. These distances are used as constraints in 100 ps molecular dynamics simulations in water using QUANTA and CHARMm. In addition, the dynamics simulations are performed without constraints. ROE build-up curves are computed from the averaged structures of the molecular dynamics simulations using the CROSREL program and compared with the experimental curves. Thus, a refinement of the initial structure may be obtained. The alpha-(1-->2) and the beta-(1-->3) links are unambiguously defined by the observed ROE cross peaks between the A-B',A'-B and C-B,C'-B' residues, respectively. The branch-point of the trisaccharide CBA' is conformationally well-defined. Assignment of the conformation of the B-A linkage (alpha-(1-->3)) was problematic due to TOCSY relay, but could be solved by NOESY and T-ROESY techniques. A conformational model for the polysaccharide is proposed.

[Advances in the research of application of hydrogels in three-dimensional bioprinting].

PubMed

Yang, J; Zhao, Y; Li, H H; Zhu, S H

2016-08-20

Hydrogels are three-dimensional networks made of hydrophilic polymer crosslinked through covalent bonds or physical intermolecular attractions, which can contain growth media and growth factors to support cell growth. In bioprinting, hydrogels are used to provide accurate control over cellular microenvironment and to dramatically reduce experimental repetition times, meanwhile we can obtain three-dimensional cell images of high quality. Hydrogels in three-dimensional bioprinting have received a considerable interest due to their structural similarities to the natural extracellular matrix and polyporous frameworks which can support the cellular proliferation and survival. Meanwhile, they are accompanied by many challenges.

Constraints on parity violating conformal field theories in d = 3

NASA Astrophysics Data System (ADS)

Chowdhury, Subham Dutta; David, Justin R.; Prakash, Shiroman

2017-11-01

We derive constraints on three-point functions involving the stress tensor, T, and a conserved U(1) current, j, in 2+1 dimensional conformal field theories that violate parity, using conformal collider bounds introduced by Hofman and Maldacena. Conformal invariance allows parity-odd tensor-structures for the 〈 T T T〉 and 〈 jjT〉 correlation functions which are unique to three space-time dimensions. Let the parameters which determine the 〈 T T T〉 correlation function be t 4 and α T , where α T is the parity-violating contribution. Similarly let the parameters which determine 〈 jjT〉 correlation function be a 2, and α J , where α J is the parity-violating contribution. We show that the parameters ( t 4, α T ) and (a2, α J ) are bounded to lie inside a disc at the origin of the t 4 - α T plane and the a 2 - α J plane respectively. We then show that large N Chern-Simons theories coupled to a fundamental fermion/boson lie on the circle which bounds these discs. The `t Hooft coupling determines the location of these theories on the boundary circles.

Higher Spin Fields in Three-Dimensional Gravity

NASA Astrophysics Data System (ADS)

Lepage-Jutier, Arnaud

In this thesis, we study the effects of massless higher spin fields in three-dimensional gravity with a negative cosmological constant. First, we introduce gravity in Anti-de Sitter (AdS) space without the higher spin gauge symmetry. We recapitulate the semi-classical analysis that outlines the duality between quantum gravity in three dimensions with a negative cosmological constant and a conformal field theory on the asymptotic boundary of AdS 3. We review the statistical interpretation of the black hole entropy via the AdS/CFT correspondence and the modular invariance of the partition function of a CFT on a torus. For the case of higher spin theories in AdS 3 we use those modular properties to bound the amount of gauge symmetry present. We then discuss briefly cases that can evade this bound.

Chromosome Conformation of Human Fibroblasts Grown in 3-Dimensional Spheroids

PubMed Central

Chen, Haiming; Comment, Nicholas; Chen, Jie; Ronquist, Scott; Hero, Alfred; Ried, Thomas; Rajapakse, Indika

2015-01-01

In the study of interphase chromosome organization, genome-wide chromosome conformation capture (Hi-C) maps are often generated using 2-dimensional (2D) monolayer cultures. These 2D cells have morphological deviations from cells that exist in 3-dimensional (3D) tissues in vivo, and may not maintain the same chromosome conformation. We used Hi-C maps to test the extent of differences in chromosome conformation between human fibroblasts grown in 2D cultures and those grown in 3D spheroids. Significant differences in chromosome conformation were found between 2D cells and those grown in spheroids. Intra-chromosomal interactions were generally increased in spheroid cells, with a few exceptions, while inter-chromosomal interactions were generally decreased. Overall, chromosomes located closer to the nuclear periphery had increased intra-chromosomal contacts in spheroid cells, while those located more centrally had decreased interactions. This study highlights the necessity to conduct studies on the topography of the interphase nucleus under conditions that mimic an in vivo environment. PMID:25738643

Magnetic diagnostics for equilibrium reconstructions in the presence of nonaxisymmetric eddy current distributions in tokamaks (invited).

PubMed

Berzak, L; Jones, A D; Kaita, R; Kozub, T; Logan, N; Majeski, R; Menard, J; Zakharov, L

2010-10-01

The lithium tokamak experiment (LTX) is a modest-sized spherical tokamak (R(0)=0.4 m and a=0.26 m) designed to investigate the low-recycling lithium wall operating regime for magnetically confined plasmas. LTX will reach this regime through a lithium-coated shell internal to the vacuum vessel, conformal to the plasma last-closed-flux surface, and heated to 300-400 °C. This structure is highly conductive and not axisymmetric. The three-dimensional nature of the shell causes the eddy currents and magnetic fields to be three-dimensional as well. In order to analyze the plasma equilibrium in the presence of three-dimensional eddy currents, an extensive array of unique magnetic diagnostics has been implemented. Sensors are designed to survive high temperatures and incidental contact with lithium and provide data on toroidal asymmetries as well as full coverage of the poloidal cross-section. The magnetic array has been utilized to determine the effects of nonaxisymmetric eddy currents and to model the start-up phase of LTX. Measurements from the magnetic array, coupled with two-dimensional field component modeling, have allowed a suitable field null and initial plasma current to be produced. For full magnetic reconstructions, a three-dimensional electromagnetic model of the vacuum vessel and shell is under development.

Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

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

Morikawa, Lisa K.; Memorial Sloan-Kettering Cancer Center; Roach, Mack, E-mail: mroach@radonc.ucsf.ed

2011-05-01

Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostatemore » cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.« less

Invariant solutions to the conformal Killing-Yano equation on Lie groups

NASA Astrophysics Data System (ADS)

Andrada, A.; Barberis, M. L.; Dotti, I. G.

2015-08-01

We search for invariant solutions of the conformal Killing-Yano equation on Lie groups equipped with left invariant Riemannian metrics, focusing on 2-forms. We show that when the Lie group is compact equipped with a bi-invariant metric or 2-step nilpotent, the only invariant solutions occur on the 3-dimensional sphere or on a Heisenberg group. We classify the 3-dimensional Lie groups with left invariant metrics carrying invariant conformal Killing-Yano 2-forms.

Carbon nanotube-based three-dimensional monolithic optoelectronic integrated system

NASA Astrophysics Data System (ADS)

Liu, Yang; Wang, Sheng; Liu, Huaping; Peng, Lian-Mao

2017-06-01

Single material-based monolithic optoelectronic integration with complementary metal oxide semiconductor-compatible signal processing circuits is one of the most pursued approaches in the post-Moore era to realize rapid data communication and functional diversification in a limited three-dimensional space. Here, we report an electrically driven carbon nanotube-based on-chip three-dimensional optoelectronic integrated circuit. We demonstrate that photovoltaic receivers, electrically driven transmitters and on-chip electronic circuits can all be fabricated using carbon nanotubes via a complementary metal oxide semiconductor-compatible low-temperature process, providing a seamless integration platform for realizing monolithic three-dimensional optoelectronic integrated circuits with diversified functionality such as the heterogeneous AND gates. These circuits can be vertically scaled down to sub-30 nm and operates in photovoltaic mode at room temperature. Parallel optical communication between functional layers, for example, bottom-layer digital circuits and top-layer memory, has been demonstrated by mapping data using a 2 × 2 transmitter/receiver array, which could be extended as the next generation energy-efficient signal processing paradigm.

The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality.

PubMed

De Wilde, Tim R W; Ten Velden, Femke S; De Dreu, Carsten K W

2017-01-11

Groups can make better decisions than individuals when members cooperatively exchange and integrate their uniquely held information and insights. However, under conformity pressures group members are biased towards exchanging commonly known information, and away from exchanging unique information, thus undermining group decision-making quality. At the neurobiological level, conformity associates with the neuropeptide oxytocin. A double-blind placebo controlled study found no evidence for oxytocin induced conformity. Compared to placebo groups, three-person groups whose members received intranasal oxytocin, focused more on unique information (i) and repeated this information more often (ii). These findings reveal oxytocin as a neurobiological driver of group decision-making processes.

The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality

PubMed Central

De Wilde, Tim R. W.; Ten Velden, Femke S.; De Dreu, Carsten K. W.

2017-01-01

Groups can make better decisions than individuals when members cooperatively exchange and integrate their uniquely held information and insights. However, under conformity pressures group members are biased towards exchanging commonly known information, and away from exchanging unique information, thus undermining group decision-making quality. At the neurobiological level, conformity associates with the neuropeptide oxytocin. A double-blind placebo controlled study found no evidence for oxytocin induced conformity. Compared to placebo groups, three-person groups whose members received intranasal oxytocin, focused more on unique information (i) and repeated this information more often (ii). These findings reveal oxytocin as a neurobiological driver of group decision-making processes. PMID:28074896

On the ambiguity of conformational states: A B&S-LEUS simulation study of the helical conformations of decaalanine in water

NASA Astrophysics Data System (ADS)

Bieler, Noah S.; Hünenberger, Philippe H.

2015-04-01

Estimating the relative stabilities of different conformational states of a (bio-)molecule using molecular dynamics simulations involves two challenging problems: the conceptual problem of how to define the states of interest and the technical problem of how to properly sample these states, along with achieving a sufficient number of interconversion transitions. In this study, the two issues are addressed in the context of a decaalanine peptide in water, by considering the 310-, α-, and π-helical states. The simulations rely on the ball-and-stick local-elevation umbrella-sampling (B&S-LEUS) method. In this scheme, the states are defined as hyperspheres (balls) in a (possibly high dimensional) collective-coordinate space and connected by hypercylinders (sticks) to ensure transitions. A new object, the pipe, is also introduced here to handle curvilinear pathways. Optimal sampling within the so-defined space is ensured by confinement and (one-dimensional) memory-based biasing potentials associated with the three different kinds of objects. The simulation results are then analysed in terms of free energies using reweighting, possibly relying on two distinct sets of collective coordinates for the state definition and analysis. The four possible choices considered for these sets are Cartesian coordinates, hydrogen-bond distances, backbone dihedral angles, or pairwise sums of successive backbone dihedral angles. The results concerning decaalanine underline that the concept of conformational state may be extremely ambiguous, and that its tentative absolute definition as a free-energy basin remains subordinated to the choice of a specific analysis space. For example, within the force-field employed and depending on the analysis coordinates selected, the 310-helical state may refer to weakly overlapping collections of conformations, differing by as much as 25 kJ mol-1 in terms of free energy. As another example, the π-helical state appears to correspond to a free-energy basin for three choices of analysis coordinates, but to be unstable with the fourth one. The problem of conformational-state definition may become even more intricate when comparison with experiment is involved, where the state definition relies on spectroscopic or functional observables.

On the ambiguity of conformational states: A B&S-LEUS simulation study of the helical conformations of decaalanine in water.

PubMed

Bieler, Noah S; Hünenberger, Philippe H

2015-04-28

Estimating the relative stabilities of different conformational states of a (bio-)molecule using molecular dynamics simulations involves two challenging problems: the conceptual problem of how to define the states of interest and the technical problem of how to properly sample these states, along with achieving a sufficient number of interconversion transitions. In this study, the two issues are addressed in the context of a decaalanine peptide in water, by considering the 310-, α-, and π-helical states. The simulations rely on the ball-and-stick local-elevation umbrella-sampling (B&S-LEUS) method. In this scheme, the states are defined as hyperspheres (balls) in a (possibly high dimensional) collective-coordinate space and connected by hypercylinders (sticks) to ensure transitions. A new object, the pipe, is also introduced here to handle curvilinear pathways. Optimal sampling within the so-defined space is ensured by confinement and (one-dimensional) memory-based biasing potentials associated with the three different kinds of objects. The simulation results are then analysed in terms of free energies using reweighting, possibly relying on two distinct sets of collective coordinates for the state definition and analysis. The four possible choices considered for these sets are Cartesian coordinates, hydrogen-bond distances, backbone dihedral angles, or pairwise sums of successive backbone dihedral angles. The results concerning decaalanine underline that the concept of conformational state may be extremely ambiguous, and that its tentative absolute definition as a free-energy basin remains subordinated to the choice of a specific analysis space. For example, within the force-field employed and depending on the analysis coordinates selected, the 310-helical state may refer to weakly overlapping collections of conformations, differing by as much as 25 kJ mol(-1) in terms of free energy. As another example, the π-helical state appears to correspond to a free-energy basin for three choices of analysis coordinates, but to be unstable with the fourth one. The problem of conformational-state definition may become even more intricate when comparison with experiment is involved, where the state definition relies on spectroscopic or functional observables.

Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling.

PubMed

Ogihara, Takuo; Kano, Takashi; Kakinuma, Chihaya

2009-01-01

Currently, a new type of calcium channel blockers, which can inhibit not only L-type calcium channels abundantly expressed in vascular smooth muscles, but also N-type calcium channels that abound in the sympathetic nerve endings, have been developed. In this study, analysis on a like-for-like basis of the L- and N-type calcium channel-inhibitory activity of typical dihydropyridine-type calcium-channel blockers (DHPs) was performed. Moreover, to understand the differences of N-type calcium channel inhibition among DHPs, the binding of DHPs to the channel was investigated by means of hypothetical three-dimensional pharmacophore modeling using multiple calculated low-energy conformers of the DHPs. All of the tested compounds, i.e. cilnidipine (CAS 132203-70-4), efonidipine (CAS 111011-76-8), amlodipine (CAS 111470-99-6), benidipine (CAS 85387-35-5), azelnidipine (CAS 123524-52-7) and nifedipine (CAS 21829-25-4), potently inhibited the L-type calcium channel, whereas only cilnidipine inhibited the N-type calcium channel (IC50 value: 51.2 nM). A virtual three-dimensional structure of the N-type calcium channel was generated by using the structure of the peptide omega-conotoxin GVIA, a standard inhibitor of the channel, and cilnidipine was found to fit well into this pharmacophore model. Lipophilic potential maps of omega-conotoxin GVIA and cilnidipine supported this finding. Conformational overlay of cilnidipine and the other DHPs indicated that amlodipine and nifedipine were not compatible with the pharmacophore model because they did not contain an aromatic ring that was functionally equivalent to Tyr13 of omega-conotoxin GVIA. Azelnidipine, benidipine, and efonidipine, which have this type of aromatic ring, were not positively identified due to intrusions into the excluded volume. Estimation of virtual three-dimensional structures of proteins, such as ion channels, by using standard substrates and/or inhibitors may be a useful method to explore the mechanisms of pharmacological and toxicological effects of substrates and/or inhibitors, and to discover new drugs.

Analysis of different fractionations of three-dimensional conformable radiotherapy for esophageal cancer.

PubMed

Ma, Zhiqian; Zhang, Yan; Chen, Xiaofang; Liu, Chaoxing; Xu, Huijun; Zhao, Peng

2015-01-01

This study aims to observe and discuss the curative and side effects of three different fractionation regimen of three-dimensional conformable radiotherapy (3DCRT) for esophageal cancer. A total of 169 untreated patients of esophageal cancer were randomized into three groups: groups A (conventional group, 2.0 Gy per time), B (2.5 Gy group, 2 Gy per time), and C (3.0 Gy group, 3.0 Gy per time), respectively. Groups A, B, and C are similar in terms of partial response (P = 0.35). However, the three groups had no significant differences in terms of the complete response (P = 0.63). The three-year survival rate of group B was higher than those of the other two groups, and the difference was significant (P = 0.047). For the three-year local control rate, that of group B was also higher than those of groups A and C, but the difference was not significant (P = 0.067). The incidence rate of 3 level esophagitis and bronchitis was highest in group C (P = 0.023 and P = 0.064). The 3 level tardive radioactive esophagitis in group C was higher than those in other two groups (P = 0.037 and P = 0.04). The incidence rate of the 3 level advanced lung reaction was also the highest in the three groups (P = 0.041). The effect is better and the side effect is tolerable for the 2.5 Gy per fraction, 5 times per week; thus, it can be used clinically for 3DCRT for esophageal carcinoma.

Glioblastoma in Children: A Single-Institution Experience

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

Perkins, Stephanie M.; Rubin, Joshua B.; Leonard, Jeffrey R.

2011-07-15

Purpose: Current treatment recommendations for pediatric glioblastoma include surgery, chemotherapy, and radiation therapy. However, even with this multispecialty approach, overall survival remains poor. To assess outcome and evaluate treatment-related prognostic factors, we retrospectively reviewed the experience at our institution. Methods and Materials: Twenty-four glioblastoma patients under the age of 21 were treated with radiation therapy with curative intent at Washington University, St. Louis, from 1970 to 2008. Patients underwent gross total resection, subtotal resection or biopsy alone. Fourteen (58%) of the patients received chemotherapy. All patients received radiation therapy. Radiation consisted of whole-brain radiation therapy in 7 (29%) patients withmore » a median dose of 50.4 Gy. Seventeen (71%) patients received three-dimensional conformal radiation therapy with a median dose of 54 Gy. Results: Median follow-up was 12.5 months from diagnosis. One and 2-year overall survival rates were 57% and 32%, respectively. Median overall survival was 13.5 months. There were no differences in overall survival based on patients' age, race, gender, tumor location, radiation volume, radiation dose, or the use of chemotherapy. There was a significant improvement in overall survival for patients in whom gross total resection was achieved (p = 0.023). Three patients were alive 5 years after gross total resection, and 2 patients were alive at 10 and 24 years after diagnosis. Conclusions: Survival for children with glioblastoma remains poor. Data from this and other studies demonstrate the importance of achieving a gross total resection. Continued investigation into new treatment options is needed in an attempt to improve outcome for these patients.« less

Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: Toxicity and clinical outcome

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

Milano, Michael T.; Jani, Ashesh B.; Farrey, Karl J.

2005-10-01

Purpose: To assess survival, local control, and toxicity of intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the anal canal. Methods and Materials: Seventeen patients were treated with nine-field IMRT plans. Thirteen received concurrent 5-fluorouracil and mitomycin C, whereas 1 patient received 5-fluorouracil alone. Seven patients were planned with three-dimensional anteroposterior/posterior-anterior (AP/PA) fields for dosimetric comparison to IMRT. Results: Compared with AP/PA, IMRT reduced the mean and threshold doses to small bowel, bladder, and genitalia. Treatment was well tolerated, with no Grade {>=}3 acute nonhematologic toxicity. There were no treatment breaks attributable to gastrointestinal or skin toxicity. Ofmore » patients who received mitomycin C, 38% experienced Grade 4 hematologic toxicity. IMRT did not afford bone marrow sparing, possibly resulting from the clinical decision to prescribe 45 Gy to the whole pelvis in most patients, vs. the Radiation Therapy Oncology Group-recommended 30.6 Gy whole pelvic dose. Three of 17 patients, who did not achieve a complete response, proceeded to an abdominoperineal resection and colostomy. At a median follow-up of 20.3 months, there were no other local failures. Two-year overall survival, disease-free survival, and colostomy-free survival are: 91%, 65%, and 82% respectively. Conclusions: In this hypothesis-generating analysis, the acute toxicity and clinical outcome with IMRT in the treatment of anal cancer is encouraging. Compared with historical controls, local control is not compromised despite efforts to increase conformality and reduce normal structure dose.« less

Dosimetric study of the protection level of the bone marrow in patients with cervical or endometrial cancer for three radiotherapy techniques - 3D CRT, IMRT and VMAT. Study protocol.

NASA Astrophysics Data System (ADS)

Jodda, Agata; Urbański, Bartosz; Piotrowski, Tomasz; Malicki, Julian

2016-03-01

Background: The paper shows the methodology of an in-phantom study of the protection level of the bone marrow in patients with cervical or endometrial cancer for three radiotherapy techniques: three-dimensional conformal radiotherapy, intensity modulated radiotherapy, and volumetric modulated arc therapy, preceded by the procedures of image guidance. Methods/Design: The dosimetric evaluation of the doses will be performed in an in-house multi-element anthropomorphic phantom of the female pelvic area created by three-dimensional printing technology. The volume and position of the structures will be regulated according to the guidelines from the Bayesian network. The input data for the learning procedure of the model will be obtained from the retrospective analysis of imaging data obtained for 96 patients with endometrial cancer or cervical cancer treated with radiotherapy in our centre in 2008-2013. Three anatomical representations of the phantom simulating three independent clinical cases will be chosen. Five alternative treatment plans (1 × three-dimensional conformal radiotherapy, 2 × intensity modulated radiotherapy and 2 × volumetric modulated arc therapy) will be created for each representation. To simulate image-guided radiotherapy, ten specific recombinations will be designated, for each anatomical representation separately, reflecting possible changes in the volume and position of the phantom components. Discussion: The comparative analysis of planned measurements will identify discrepancies between calculated doses and doses that were measured in the phantom. Finally, differences between the doses cumulated in the hip plates performed by different techniques simulating the gynaecological patients' irradiation of dose delivery will be established. The results of this study will form the basis of the prospective clinical trial that will be designed for the assessment of hematologic toxicity and its correlation with the doses cumulated in the hip plates, for gynaecologic patients undergoing radiation therapy.

Computational conformational antimicrobial analysis developing mechanomolecular theory for polymer biomaterials in materials science and engineering

NASA Astrophysics Data System (ADS)

Petersen, Richard C.

2014-03-01

Single-bond rotations or pyramidal inversions tend to either hide or expose relative energies that exist for atoms with nonbonding lone-pair electrons. Availability of lone-pair electrons depends on overall molecular electron distributions and differences in the immediate polarity of the surrounding pico/nanoenvironment. Stereochemistry three-dimensional aspects of molecules provide insight into conformations through single-bond rotations with associated lone-pair electrons on oxygen atoms in addition to pyramidal inversions with nitrogen atoms. When electrons are protected, potential energy is sheltered toward an energy minimum value to compatibilize molecularly with nonpolar environments. When electrons are exposed, maximum energy is available toward polar environment interactions. Computational conformational analysis software calculated energy profiles that exist during specific oxygen ether single-bond rotations with easy-to-visualize three-dimensional models for the trichlorinated bisaromatic ether triclosan antimicrobial polymer additive. As shown, fluctuating alternating bond rotations can produce complex interactions between molecules to provide entanglement strength for polymer toughness or alternatively disrupt weak secondary bonds of attraction to lower resin viscosity for new additive properties with nonpolar triclosan as a hydrophobic toughening/wetting agent. Further, bond rotations involving lone-pair electrons by a molecule at a nonpolar-hydrocarbon-membrane/polar-biologic-fluid interface might become sufficiently unstable to provide free mechanomolecular energies to disrupt weaker microbial membranes, for membrane transport of molecules into cells, provide cell signaling/recognition/defense and also generate enzyme mixing to speed reactions.

Entropic Elasticity in the Giant Muscle Protein Titin

NASA Astrophysics Data System (ADS)

Morgan, Ian; Saleh, Omar

Intrinsically disordered proteins (IDPs) are a large and functionally important class of proteins that lack a fixed three-dimensional structure. Instead, they adopt a conformational ensemble of states which facilitates their biological function as molecular linkers, springs, and switches. Due to their conformational flexibility, it can be difficult to study IDPs using typical experimental methods. To overcome this challenge, we use a high-resolution single-molecule magnetic stretching technique to quantify IDP flexibility. We apply this technique to the giant muscle protein titin, measuring its elastic response at low forces. We present results demonstrating that titin's native elastic response derives from the combined entropic elasticity of its ordered and disordered domains.

Solution conformation of a peptide fragment representing a proposed RNA-binding site of a viral coat protein studied by two-dimensional NMR

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

van der Graaf, M.; van Mierlo, C.P.M.; Hemminga, M.A.

1991-06-11

The first 25 amino acids of the coat protein of cowpea chlorotic mottle virus are essential for binding the encapsidated RNA. Although an {alpha}-helical conformation has been predicted for this highly positively charged N-terminal region. No experimental evidence for this conformation has been presented so far. In this study, two-dimensional proton NMR experiments were performed on a chemically synthesized pentacosapeptide containing the first 25 amino acids of this coat protein. All resonances could be assigned by a combined use of two-dimensional correlated spectroscopy and nuclear Overhauser enhancement spectroscopy carried out at four different temperatures. Various NMR parameters indicate the presencemore » of a conformational ensemble consisting of helical structures rapidly converting into more extended states. Differences in chemical shifts and nuclear Overhauser effects indicate that lowering the temperature induces a shift of the dynamic equilibrium toward more helical structures. At 10{degrees}C, a perceptible fraction of the conformational ensemble consists of structures with an {alpha}-helical conformation between residues 9 and 17, likely starting with a turnlike structure around Thr9 and Arg10. Both the conformation and the position of this helical region agree well with the secondary structure predictions mentioned above.« less

Free energy landscapes of peptides by enhanced conformational sampling.

PubMed

Nakajima, N; Higo, J; Kidera, A; Nakamura, H

2000-02-11

The free energy landscapes of peptide conformations in water have been observed by the enhanced conformational sampling method, applying the selectively enhanced multicanonical molecular dynamics simulations. The conformations of the peptide dimers, -Gly-Gly-, -Gly-Ala-, -Gly-Ser-, -Ala-Gly-, -Asn-Gly-, -Pro-Gly-, -Pro-Ala-, and -Ala-Ala-, which were all blocked with N-terminal acetyl and C-terminal N-methyl groups, were individually sampled with the explicit TIP3P water molecules. From each simulation trajectory, we obtained the canonical ensemble at 300 K, from which the individual three-dimensional landscape was drawn by the potential of mean force using the three reaction coordinates: the backbone dihedral angle, psi, of the first amino acid, the backbone dihedral angle, phi, of the second amino acid, and the distance between the carbonyl oxygen of the N-terminal acetyl group and the C-terminal amide proton. The most stable state and several meta-stable states correspond to extended conformations and typical beta-turn conformations, and their free energy values were accounted for from the potentials of mean force at the states. In addition, the contributions from the intra-molecular energies of peptides and those from the hydration effects were analyzed. Consequently, the stable beta-turn conformations in the free energy landscape were consistent with the empirically preferred beta-turn types for each amino acid sequence. The thermodynamic values for the hydration effect were decomposed and they correlated well with the empirical values estimated from the solvent accessible surface area of each molecular conformation during the trajectories. The origin of the architecture of protein local fragments was analyzed from the viewpoint of the free energy and its decomposed factors. Copyright 2000 Academic Press.

Positron emission tomography-guided conformal fast neutron therapy for glioblastoma multiforme

PubMed Central

Stelzer, Keith J.; Douglas, James G.; Mankoff, David A.; Silbergeld, Daniel L.; Krohn, Kenneth A.; Laramore, George E.; Spence, Alexander M.

2008-01-01

Glioblastoma multiforme (GBM) continues to be a difficult therapeutic challenge. Our study was conducted to determine whether improved survival and tumor control could be achieved with modern delivery of fast neutron radiation using three-dimensional treatment planning. Ten patients were enrolled. Eligibility criteria included pathologic diagnosis of GBM, age ≥ 18 years, and KPS ≥60. Patients underwent MRI and 18F-fluorodeoxyglucose PET (FDG PET) as part of initial three-dimensional treatment planning. Sequential targets were treated with noncoplanar fields to a total dose of 18 Gy in 16 fractions over 4 weeks. Median and 1-year overall survival were 55 weeks and 60%, respectively. One patient remains alive at last follow-up 255 weeks after diagnosis. Median progression-free survival was 16 weeks, and all patients had tumor progression by 39 weeks. Treatment was clinically well tolerated, but evidence of mild to moderate gliosis and microvascular sclerosis consistent with radiation injury was observed at autopsy in specimens taken from regions of contralateral brain that received approximately 6–10 Gy. Fast neutron radiation using modern imaging, treatment planning, and beam delivery was feasible to a total dose of 18 Gy, but tumor control probability was poor in comparison to that predicted from a dose-response model based on older studies. Steep dose-response curves for both tumor control and neurotoxicity continue to present a challenge to establishing a therapeutic window for fast neutron radiation in GBM, even with modern techniques. PMID:18055860

Universal thermal corrections to single interval entanglement entropy for two dimensional conformal field theories.

PubMed

Cardy, John; Herzog, Christopher P

2014-05-02

We consider single interval Rényi and entanglement entropies for a two dimensional conformal field theory on a circle at nonzero temperature. Assuming that the finite size of the system introduces a unique ground state with a nonzero mass gap, we calculate the leading corrections to the Rényi and entanglement entropy in a low temperature expansion. These corrections have a universal form for any two dimensional conformal field theory that depends only on the size of the mass gap and its degeneracy. We analyze the limits where the size of the interval becomes small and where it becomes close to the size of the spatial circle.

Enhancing Three-dimensional Movement Control System for Assemblies of Machine-Building Facilities

NASA Astrophysics Data System (ADS)

Kuzyakov, O. N.; Andreeva, M. A.

2018-01-01

Aspects of enhancing three-dimensional movement control system are given in the paper. Such system is to be used while controlling assemblies of machine-building facilities, which is a relevant issue. The base of the system known is three-dimensional movement control device with optical principle of action. The device consists of multi point light emitter and light receiver matrix. The processing of signals is enhanced to increase accuracy of measurements by switching from discrete to analog signals. Light receiver matrix is divided into four areas, and the output value of each light emitter in each matrix area is proportional to its luminance level. Thus, determing output electric signal value of each light emitter in corresponding area leads to determing position of multipoint light emitter and position of object tracked. This is done by using Case-based reasoning method, the precedent in which is described as integral signal value of each matrix area, coordinates of light receivers, which luminance level is high, and decision to be made in this situation.

More on asymptotically anti-de Sitter spaces in topologically massive gravity

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

Henneaux, Marc; Physique theorique et mathematique, Universite Libre de Bruxelles and International Solvay Institutes, ULB Campus Plaine C.P. 231, B-1050 Bruxelles; Martinez, Cristian

2010-09-15

Recently, the asymptotic behavior of three-dimensional anti-de Sitter (AdS) gravity with a topological mass term was investigated. Boundary conditions were given that were asymptotically invariant under the two dimensional conformal group and that included a falloff of the metric sufficiently slow to consistently allow pp-wave type of solutions. Now, pp waves can have two different chiralities. Above the chiral point and at the chiral point, however, only one chirality can be considered, namely, the chirality that has the milder behavior at infinity. The other chirality blows up faster than AdS and does not define an asymptotically AdS spacetime. By contrast,more » both chiralities are subdominant with respect to the asymptotic behavior of AdS spacetime below the chiral point. Nevertheless, the boundary conditions given in the earlier treatment only included one of the two chiralities (which could be either one) at a time. We investigate in this paper whether one can generalize these boundary conditions in order to consider simultaneously both chiralities below the chiral point. We show that this is not possible if one wants to keep the two-dimensional conformal group as asymptotic symmetry group. Hence, the boundary conditions given in the earlier treatment appear to be the best possible ones compatible with conformal symmetry. In the course of our investigations, we provide general formulas controlling the asymptotic charges for all values of the topological mass (not just below the chiral point).« less

Lung reexpansion of obstructive atelectasis caused by radiotherapy after continuous gefitinib treatment in nonsmall cell lung cancer.

PubMed

Yang, Xueqin; Xu, Mingfang; Xiong, Yanli; Peng, Bo

2015-01-01

A 75-year-old male was diagnosed with central squamous cell carcinoma of the left lung, who has been given 3-dimensional conformal radiotherapy of total dose with 60 Gy in 30 fractions. Three years later, the tumor relapsed in situ and he received another stereotactic radiotherapy with a total dose of 40 Gy at a margin of planning target volume (PTV) in 10 (5 fractions/week) at 4 Gy/fraction. Gefitinib (250 mg/day) was initiated immediately after radiotherapy. Obstructive atelectasis in the left lung and increased pleural effusion occurred at the fourth month after radiotherapy. As this patient has been detected with deletion in exon 19 of the EGFR gene, gefitinib was continuous administered without interruption. After another 4 months, the atelectasis in the left lung reexpanded significantly. To the best of our knowledge, this is the first report in the literature that EGFR tyrosine kinase inhibitors (EGFR-TKI) reversed the radiation atelectasis of pulmonary in the nonsmall cell lung cancer (NSCLC) patient.

Filling the gap: Micro-C accesses the nucleosomal fiber at 100-1000 bp resolution.

PubMed

Mozziconacci, Julien; Koszul, Romain

2015-08-21

The fine three-dimensional structure of the nucleosomal fiber has remained elusive to genome-wide chromosome conformation capture (3C) approaches. A new study mapping contacts at the single nucleosome level (Micro-C) reveals topological interacting domains along budding yeast chromosomes. These domains encompass one to five consecutive genes and are delimited by highly active promoters.

Three Dimensional Architecture of Membrane-Embedded MscS in the Closed Conformation

PubMed Central

Vásquez, Valeria; Sotomayor, Marcos; Cortes, D. Marien; Roux, Benoît; Schulten, Klaus; Perozo, Eduardo

2009-01-01

The mechanosensitive channel of small conductance (MscS) is part of a coordinated response to osmotic challenges in E. coli. MscS opens as a result of membrane tension changes, thereby releasing small solutes and effectively acting as an osmotic safety valve. Both, the functional state depicted by its crystal structure and its gating mechanism remain unclear. Here, we combine site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy, and molecular dynamics simulations with novel energy restraints based on experimental EPR data to investigate the native transmembrane and periplasmic molecular architecture of closed MscS in a lipid bilayer. In the closed conformation, MscS shows a more compact transmembrane domain than in the crystal structure, characterized by a realignment of the transmembrane segments towards the normal of the membrane. The previously unresolved NH2-terminus forms a short helical hairpin capping the extracellular ends of TM1 and TM2 and in close interaction with the bilayer interface. The present three-dimensional model of membrane-embedded MscS in the closed state represents a key step in determining the molecular mechanism of MscS gating. PMID:18343404

[Intensity-modulated or 3-D conformal radiotherapy combined with chemotherapy with docetaxel and cisplatin for locally advanced esophageal carcinoma].

PubMed

Lin, Xiao-dan; Shi, Xing-yuan; Zhou, Tong-chong; Zhang, Wei-jun

2011-06-01

To evaluate the therapeutic effect and toxicity of intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy combined with chemotherapy (3-DCRT) with docetaxel and cisplatin in the treatment of locally advanced esophageal carcinoma. Sixty patients with locally advanced esophageal carcinoma were randomly assigned in two equal groups to receive IMRT or 3-DCRT, both combined with the chemotherapy with docetaxel and cisplatin. The total dose of radiotherapy was 64 Gy, administered in 30 fractions in 6 weeks. The complete response rate (complete and partial remissions) of IMRT group was 90.0%, significantly higher than the rate of 80.0% in 3-DCRT group (P>0.05). The 1-, 2-, and 3-year survival rates of IMRT group were 86.7%, 70.0%, and 66.7%, as compared to 70.0%, 63.3%, and 63.3% in 3-DCRT group, respectively, showing no significant differences between the two groups (P>0.05). IMRT showed advantages over 3-DCRT in terms of the V20 and V30 parameters of the lung (P<0.05), and the incidences of radiation-induced esophagitis were comparable between the two groups (P>0.05). When combined with the chemotherapy with docetaxel and cisplatin, IMRT appears to be a more effective treatment than 3-DCRT for locally advanced esophageal cancer.

Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

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

Quero, Laurent, E-mail: laurent.quero@sls.aphp.fr; Bouchbika, Zineb; Kouto, Honorine

2012-06-01

Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes atmore » 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m Superscript-Two ) followed by a bolus of 5-fluorouracil (400 mg/m Superscript-Two ) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m Superscript-Two ) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.« less

Bridging the Resolution Gap in Structural Modeling of 3D Genome Organization

PubMed Central

Marti-Renom, Marc A.; Mirny, Leonid A.

2011-01-01

Over the last decade, and especially after the advent of fluorescent in situ hybridization imaging and chromosome conformation capture methods, the availability of experimental data on genome three-dimensional organization has dramatically increased. We now have access to unprecedented details of how genomes organize within the interphase nucleus. Development of new computational approaches to leverage this data has already resulted in the first three-dimensional structures of genomic domains and genomes. Such approaches expand our knowledge of the chromatin folding principles, which has been classically studied using polymer physics and molecular simulations. Our outlook describes computational approaches for integrating experimental data with polymer physics, thereby bridging the resolution gap for structural determination of genomes and genomic domains. PMID:21779160

Three-dimensional structure of phosphoribosyl pyrophosphate synthetase from E. coli at 2.71 Å resolution

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

Timofeev, V. I., E-mail: inna@ns.crys.ras.ru, E-mail: tostars@mail.ru, E-mail: ugama@yandex.ru; Abramchik, Yu. A.; Zhukhlistova, N. E.

2016-01-15

Phosphoribosyl pyrophosphate synthetase from Escherichia coli was cloned, purified, and crystallized. Single crystals of the enzyme were grown under microgravity. The X-ray diffraction data set was collected at the Spring-8 synchrotron facility and used to determine the three-dimensional structure of the enzyme by the molecular-replacement method at 2.71 Å resolution. The active and regulatory sites in the molecule of E. coli phosphoribosyl pyrophosphate synthetase were revealed by comparison with the homologous protein from Bacillus subtilis, the structure of which was determined in a complex with functional ligands. The conformations of polypeptide-chain fragments surrounding and composing the active and regulatory sitesmore » were shown to be identical in both proteins.« less

Three-dimensional structural analysis of eukaryotic flagella/cilia by electron cryo-tomography

PubMed Central

Bui, Khanh Huy; Pigino, Gaia; Ishikawa, Takashi

2011-01-01

Electron cryo-tomography is a potential approach to analyzing the three-dimensional conformation of frozen hydrated biological macromolecules using electron microscopy. Since projections of each individual object illuminated from different orientations are merged, electron tomography is capable of structural analysis of such heterogeneous environments as in vivo or with polymorphism, although radiation damage and the missing wedge are severe problems. Here, recent results on the structure of eukaryotic flagella, which is an ATP-driven bending organelle, from green algae Chlamydomonas are presented. Tomographic analysis reveals asymmetric molecular arrangements, especially that of the dynein motor proteins, in flagella, giving insight into the mechanism of planar asymmetric bending motion. Methodological challenges to obtaining higher-resolution structures from this technique are also discussed. PMID:21169680

Universal statistics of vortex tangles in three-dimensional random waves

NASA Astrophysics Data System (ADS)

Taylor, Alexander J.

2018-02-01

The tangled nodal lines (wave vortices) in random, three-dimensional wavefields are studied as an exemplar of a fractal loop soup. Their statistics are a three-dimensional counterpart to the characteristic random behaviour of nodal domains in quantum chaos, but in three dimensions the filaments can wind around one another to give distinctly different large scale behaviours. By tracing numerically the structure of the vortices, their conformations are shown to follow recent analytical predictions for random vortex tangles with periodic boundaries, where the local disorder of the model ‘averages out’ to produce large scale power law scaling relations whose universality classes do not depend on the local physics. These results explain previous numerical measurements in terms of an explicit effect of the periodic boundaries, where the statistics of the vortices are strongly affected by the large scale connectedness of the system even at arbitrarily high energies. The statistics are investigated primarily for static (monochromatic) wavefields, but the analytical results are further shown to directly describe the reconnection statistics of vortices evolving in certain dynamic systems, or occurring during random perturbations of the static configuration.

Individualized Margins in 3D Conformal Radiotherapy Planning for Lung Cancer: Analysis of Physiological Movements and Their Dosimetric Impacts

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

Germain, Francois; Beaulieu, Luc; Fortin, Andre

2008-04-01

In conformal radiotherapy planning for lung cancer, respiratory movements are not taken into account when a single computed tomography (CT) scan is performed. This study examines tumor movements to design individualized margins to account for these movements and evaluates their dosimetric impacts on planning volume. Fifteen patients undergoing CT-based planning for radical radiotherapy for localized lung cancer formed the study cohort. A reference plan was constructed based on reference gross, clinical, and planning target volumes (rGTV, rCTV, and rPTV, respectively). The reference plans were compared with individualized plans using individualized margins obtained by using 5 serial CT scans to generatemore » individualized target volumes (iGTV, iCTV, and iPTV). Three-dimensional conformal radiation therapy was used for plan generation using 6- and 23-MV photon beams. Ten plans for each patient were generated and dose-volume histograms (DVHs) were calculated. Comparisons of volumetric and dosimetric parameters were performed using paired Student t-tests. Relative to the rGTV, the total volume occupied by the superimposed GTVs increased progressively with each additional CT scans. With the use of all 5 scans, the average increase in GTV was 52.1%. For the plans with closest dosimetric coverage, target volume was smaller (iPTV/rPTV ratio 0.808) but lung irradiation was only slightly decreased. Reduction in the proportion of lung tissue that received 20 Gy or more outside the PTV (V20) was observed both for 6-MV plans (-0.73%) and 23-MV plans (-0.65%), with p = 0.02 and p = 0.04, respectively. In conformal RT planning for the treatment of lung cancer, the use of serial CT scans to evaluate respiratory motion and to generate individualized margins to account for these motions produced only a limited lung sparing advantage.« less

Hawking radiation of five-dimensional charged black holes with scalar fields

NASA Astrophysics Data System (ADS)

Miao, Yan-Gang; Xu, Zhen-Ming

2017-09-01

We investigate the Hawking radiation cascade from the five-dimensional charged black hole with a scalar field coupled to higher-order Euler densities in a conformally invariant manner. We give the semi-analytic calculation of greybody factors for the Hawking radiation. Our analysis shows that the Hawking radiation cascade from this five-dimensional black hole is extremely sparse. The charge enhances the sparsity of the Hawking radiation, while the conformally coupled scalar field reduces this sparsity.

Three-dimensional Architecture of Hair-bundle Linkages Revealed by Electron-microscopic Tomography

PubMed Central

Auer, Manfred; Koster, Abrahram J.; Ziese, Ulrike; Bajaj, Chandrajit; Volkmann, Niels; Wang, Da Neng

2008-01-01

The senses of hearing and balance rest upon mechanoelectrical transduction by the hair bundles of hair cells in the inner ear. Located at the apical cellular surface, each hair bundle comprises several tens of stereocilia and a single kinocilium that are interconnected by extracellular proteinaceous links. Using electron-microscopic tomography of bullfrog saccular sensory epithelia, we examined the three-dimensional structures of basal links, kinociliary links, and tip links. We observed significant differences in the appearances and dimensions of these three structures and found two distinct populations of tip links suggestive of the involvement of different proteins, splice variants, or protein–protein interactions. We noted auxiliary links connecting the upper portions of tip links to the taller stereocilia. Tip links and auxiliary links show a tendency to adopt a globular conformation when disconnected from the membrane surface. PMID:18421501

Skin-sparing Helical Tomotherapy vs 3D-conformal Radiotherapy for Adjuvant Breast Radiotherapy: In Vivo Skin Dosimetry Study

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

Capelle, Lisa; Warkentin, Heather; MacKenzie, Marc

Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT theremore » was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients receiving adjuvant breast RT.« less

A Novel Method Using Abstract Convex Underestimation in Ab-Initio Protein Structure Prediction for Guiding Search in Conformational Feature Space.

PubMed

Hao, Xiao-Hu; Zhang, Gui-Jun; Zhou, Xiao-Gen; Yu, Xu-Feng

2016-01-01

To address the searching problem of protein conformational space in ab-initio protein structure prediction, a novel method using abstract convex underestimation (ACUE) based on the framework of evolutionary algorithm was proposed. Computing such conformations, essential to associate structural and functional information with gene sequences, is challenging due to the high-dimensionality and rugged energy surface of the protein conformational space. As a consequence, the dimension of protein conformational space should be reduced to a proper level. In this paper, the high-dimensionality original conformational space was converted into feature space whose dimension is considerably reduced by feature extraction technique. And, the underestimate space could be constructed according to abstract convex theory. Thus, the entropy effect caused by searching in the high-dimensionality conformational space could be avoided through such conversion. The tight lower bound estimate information was obtained to guide the searching direction, and the invalid searching area in which the global optimal solution is not located could be eliminated in advance. Moreover, instead of expensively calculating the energy of conformations in the original conformational space, the estimate value is employed to judge if the conformation is worth exploring to reduce the evaluation time, thereby making computational cost lower and the searching process more efficient. Additionally, fragment assembly and the Monte Carlo method are combined to generate a series of metastable conformations by sampling in the conformational space. The proposed method provides a novel technique to solve the searching problem of protein conformational space. Twenty small-to-medium structurally diverse proteins were tested, and the proposed ACUE method was compared with It Fix, HEA, Rosetta and the developed method LEDE without underestimate information. Test results show that the ACUE method can more rapidly and more efficiently obtain the near-native protein structure.

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

Cho, Kwan Ho; Ahn, Sung Ja; Pyo, Hong Ryull

Purpose: We evaluated the efficacy of synchronous three-dimensional (3D) conformal boost to the gross tumor volume (GTV) in concurrent chemoradiotherapy for patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligibility included unresectable Stage III NSCLC with no pleural effusion, no supraclavicular nodal metastases, and Eastern Cooperative Oncology Group performance score of 0-1. Forty-nine patients with pathologically proven NSCLC were enrolled. Eighteen patients had Stage IIIA and 31 had Stage IIIB. By using 3D conformal radiotherapy (RT) techniques, a dose of 1.8 Gy was delivered to the planning target volume with a synchronous boost of 0.6 Gy tomore » the GTV, with a total dose of 60 Gy to the GTV and 45 Gy to the planning target volume in 25 fractions during 5 weeks. All patients received weekly chemotherapy consisting of paclitaxel and carboplatin during RT. Results: With a median follow-up of 36.8 months (range, 29.0-45.5 months) for surviving patients, median survival was 28.1 months. One-, 2- and 3-year overall survival rates were 77%, 56.4%, and 43.8%, respectively. Corresponding local progression-free survival rates were 71.2%, 53.7%, and 53.7%. Compliance was 90% for RT and 88% for chemotherapy. Acute esophagitis of Grade 2 or higher occurred in 29 patients. Two patients with T4 lesions died of massive bleeding and hemoptysis during treatment (Grade 5). Overall late toxicity was acceptable. Conclusions: Based on the favorable outcome with acceptable toxicity, the acceleration scheme using 3D conformal GTV boost in this trial is warranted to compare with conventional fractionation in a Phase III trial.« less

Numerical estimation of structure constants in the three-dimensional Ising conformal field theory through Markov chain uv sampler

NASA Astrophysics Data System (ADS)

Herdeiro, Victor

2017-09-01

Herdeiro and Doyon [Phys. Rev. E 94, 043322 (2016), 10.1103/PhysRevE.94.043322] introduced a numerical recipe, dubbed uv sampler, offering precise estimations of the conformal field theory (CFT) data of the planar two-dimensional (2D) critical Ising model. It made use of scale invariance emerging at the critical point in order to sample finite sublattice marginals of the infinite plane Gibbs measure of the model by producing holographic boundary distributions. The main ingredient of the Markov chain Monte Carlo sampler is the invariance under dilation. This paper presents a generalization to higher dimensions with the critical 3D Ising model. This leads to numerical estimations of a subset of the CFT data—scaling weights and structure constants—through fitting of measured correlation functions. The results are shown to agree with the recent most precise estimations from numerical bootstrap methods [Kos, Poland, Simmons-Duffin, and Vichi, J. High Energy Phys. 08 (2016) 036, 10.1007/JHEP08(2016)036].

Fast preconditioned multigrid solution of the Euler and Navier-Stokes equations for steady, compressible flows

NASA Astrophysics Data System (ADS)

Caughey, David A.; Jameson, Antony

2003-10-01

New versions of implicit algorithms are developed for the efficient solution of the Euler and Navier-Stokes equations of compressible flow. The methods are based on a preconditioned, lower-upper (LU) implementation of a non-linear, symmetric Gauss-Seidel (SGS) algorithm for use as a smoothing algorithm in a multigrid method. Previously, this method had been implemented for flows in quasi-one-dimensional ducts and for two-dimensional flows past airfoils on boundary-conforming O-type grids for a variety of symmetric limited positive (SLIP) spatial approximations, including the scalar dissipation and convective upwind split pressure (CUSP) schemes. Here results are presented for both inviscid and viscous (laminar) flows past airfoils on boundary-conforming C-type grids. The method is significantly faster than earlier explicit or implicit methods for inviscid problems, allowing solution of these problems to the level of truncation error in three to five multigrid cycles. Viscous solutions still require as many as twenty multigrid cycles.

Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution.

PubMed

Comitani, Federico; Rossi, Kevin; Ceriotti, Michele; Sanz, M Eugenia; Molteni, Carla

2017-04-14

The conformational free energy landscape of aspartic acid, a proteogenic amino acid involved in a wide variety of biological functions, was investigated as an example of the complexity that multiple rotatable bonds produce even in relatively simple molecules. To efficiently explore such a landscape, this molecule was studied in the neutral and zwitterionic forms, in the gas phase and in water solution, by means of molecular dynamics and the enhanced sampling method metadynamics with classical force-fields. Multi-dimensional free energy landscapes were reduced to bi-dimensional maps through the non-linear dimensionality reduction algorithm sketch-map to identify the energetically stable conformers and their interconnection paths. Quantum chemical calculations were then performed on the minimum free energy structures. Our procedure returned the low energy conformations observed experimentally in the gas phase with rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573 (2010)]. Moreover, it provided information on higher energy conformers not accessible to experiments and on the conformers in water. The comparison between different force-fields and quantum chemical data highlighted the importance of the underlying potential energy surface to accurately capture energy rankings. The combination of force-field based metadynamics, sketch-map analysis, and quantum chemical calculations was able to produce an exhaustive conformational exploration in a range of significant free energies that complements the experimental data. Similar protocols can be applied to larger peptides with complex conformational landscapes and would greatly benefit from the next generation of accurate force-fields.

Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution

NASA Astrophysics Data System (ADS)

Comitani, Federico; Rossi, Kevin; Ceriotti, Michele; Sanz, M. Eugenia; Molteni, Carla

2017-04-01

The conformational free energy landscape of aspartic acid, a proteogenic amino acid involved in a wide variety of biological functions, was investigated as an example of the complexity that multiple rotatable bonds produce even in relatively simple molecules. To efficiently explore such a landscape, this molecule was studied in the neutral and zwitterionic forms, in the gas phase and in water solution, by means of molecular dynamics and the enhanced sampling method metadynamics with classical force-fields. Multi-dimensional free energy landscapes were reduced to bi-dimensional maps through the non-linear dimensionality reduction algorithm sketch-map to identify the energetically stable conformers and their interconnection paths. Quantum chemical calculations were then performed on the minimum free energy structures. Our procedure returned the low energy conformations observed experimentally in the gas phase with rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573 (2010)]. Moreover, it provided information on higher energy conformers not accessible to experiments and on the conformers in water. The comparison between different force-fields and quantum chemical data highlighted the importance of the underlying potential energy surface to accurately capture energy rankings. The combination of force-field based metadynamics, sketch-map analysis, and quantum chemical calculations was able to produce an exhaustive conformational exploration in a range of significant free energies that complements the experimental data. Similar protocols can be applied to larger peptides with complex conformational landscapes and would greatly benefit from the next generation of accurate force-fields.

Close range fault tolerant noncontacting position sensor

DOEpatents

Bingham, D.N.; Anderson, A.A.

1996-02-20

A method and system are disclosed for locating the three dimensional coordinates of a moving or stationary object in real time. The three dimensional coordinates of an object in half space or full space are determined based upon the time of arrival or phase of the wave front measured by a plurality of receiver elements and an established vector magnitudes proportional to the measured time of arrival or phase at each receiver element. The coordinates of the object are calculated by solving a matrix equation or a set of closed form algebraic equations. 3 figs.

Using the global positioning satellite system to determine attitude rates using doppler effects

NASA Technical Reports Server (NTRS)

Campbell, Charles E. (Inventor)

2003-01-01

In the absence of a gyroscope, the attitude and attitude rate of a receiver can be determined using signals received by antennae on the receiver. Based on the signals received by the antennae, the Doppler difference between the signals is calculated. The Doppler difference may then be used to determine the attitude rate. With signals received from two signal sources by three antennae pairs, the three-dimensional attitude rate is determined.

Holographic derivation of entanglement entropy from the anti-de Sitter space/conformal field theory correspondence.

PubMed

Ryu, Shinsei; Takayanagi, Tadashi

2006-05-12

A holographic derivation of the entanglement entropy in quantum (conformal) field theories is proposed from anti-de Sitter/conformal field theory (AdS/CFT) correspondence. We argue that the entanglement entropy in d + 1 dimensional conformal field theories can be obtained from the area of d dimensional minimal surfaces in AdS(d+2), analogous to the Bekenstein-Hawking formula for black hole entropy. We show that our proposal agrees perfectly with the entanglement entropy in 2D CFT when applied to AdS(3). We also compare the entropy computed in AdS(5)XS(5) with that of the free N=4 super Yang-Mills theory.

Conformal Yano-Killing Tensors for Space-times with Cosmological Constant

NASA Astrophysics Data System (ADS)

Czajka, P.; Jezierski, J.

We present a new method for constructing conformal Yano-Killing tensors in five-di\\-men\\-sio\\-nal Anti-de Sitter space-time. The found tensors are represented in two different coordinate systems. We also discuss, in terms of CYK tensors, global charges which are well defined for asymptotically (five-dimensional) Anti-de Sitter space-time. Additionally in Appendix we present our own derivation of conformal Killing one-forms in four-dimensional Anti-de Sitter space-time as an application of the Theorem presented in the paper.

Novel 16-channel receive coil array for accelerated upper airway MRI at 3 Tesla.

PubMed

Kim, Yoon-Chul; Hayes, Cecil E; Narayanan, Shrikanth S; Nayak, Krishna S

2011-06-01

Upper airway MRI can provide a noninvasive assessment of speech and swallowing disorders and sleep apnea. Recent work has demonstrated the value of high-resolution three-dimensional imaging and dynamic two-dimensional imaging and the importance of further improvements in spatio-temporal resolution. The purpose of the study was to describe a novel 16-channel 3 Tesla receive coil that is highly sensitive to the human upper airway and investigate the performance of accelerated upper airway MRI with the coil. In three-dimensional imaging of the upper airway during static posture, 6-fold acceleration is demonstrated using parallel imaging, potentially leading to capturing a whole three-dimensional vocal tract with 1.25 mm isotropic resolution within 9 sec of sustained sound production. Midsagittal spiral parallel imaging of vocal tract dynamics during natural speech production is demonstrated with 2 × 2 mm(2) in-plane spatial and 84 ms temporal resolution. Copyright © 2010 Wiley-Liss, Inc.

Large-D gravity and low-D strings.

PubMed

Emparan, Roberto; Grumiller, Daniel; Tanabe, Kentaro

2013-06-21

We show that in the limit of a large number of dimensions a wide class of nonextremal neutral black holes has a universal near-horizon limit. The limiting geometry is the two-dimensional black hole of string theory with a two-dimensional target space. Its conformal symmetry explains the properties of massless scalars found recently in the large-D limit. For black branes with string charges, the near-horizon geometry is that of the three-dimensional black strings of Horne and Horowitz. The analogies between the α' expansion in string theory and the large-D expansion in gravity suggest a possible effective string description of the large-D limit of black holes. We comment on applications to several subjects, in particular to the problem of critical collapse.

Toda theory from six dimensions

NASA Astrophysics Data System (ADS)

Córdova, Clay; Jafferis, Daniel L.

2017-12-01

We describe a compactification of the six-dimensional (2,0) theory on a foursphere which gives rise to a two-dimensional Toda theory at long distances. This construction realizes chiral Toda fields as edge modes trapped near the poles of the sphere. We relate our setup to compactifications of the (2,0) theory on the five and six-sphere. In this way, we explain a connection between half-BPS operators of the (2,0) theory and twodimensional W-algebras, and derive an equality between their conformal anomalies. As we explain, all such relationships between the six-dimensional (2,0) theory and Toda field theory can be interpreted as statements about the edge modes of complex Chern-Simons on various three-manifolds with boundary.

Synthesis of potent G-quadruplex binders of macrocyclic heptaoxazole and evaluation of their activities.

PubMed

Tera, Masayuki; Iida, Keisuke; Shin-ya, Kazuo; Nagasawa, Kazuo

2009-01-01

Guanine-rich DNA sequences form unique three-dimensional conformation known as G-quadruplexes (G-q). G-q structures have been found in telomere and in some oncogene promoter. Recently, it was suggested that G-q showed some biological activities including telomere shortening and transcriptional regulation. In this paper, we synthesized selective G-q binders and evaluated of their biological activities.

4-Benzyl-4-ethyl-morpholin-1-ium hexa-fluoro-phosphate.

PubMed

Yang, Fang; Zang, Hongjun; Cheng, Bowen; Xu, Xianlin; Ren, Yuanlin

2012-03-01

The asymmetric unit of the title compound, C(13)H(20)NO(+)·PF(6) (-), contains two cations, one complete anion and two half hexa-fluoro-phosphate anions having crystallographically imposed twofold rotation symmetry. In the cations, the morpholine rings are in a chair conformation. In the crystal, ions are linked by weak C-H⋯F hydrogen bonds into a three-dimensional network.

Predictors of Long-Term Toxicity Using Three-Dimensional Conformal External Beam Radiotherapy to Deliver Accelerated Partial Breast Irradiation

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

Shaitelman, Simona F.; Kim, Leonard H.; Grills, Inga S.

Purpose: We analyzed variables associated with long-term toxicity using three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation. Methods and Materials: One hundred patients treated with 3D-CRT accelerated partial breast irradiation were evaluated using Common Terminology Criteria for Adverse Events version 4.0 scale. Cosmesis was scored using Harvard criteria. Multiple dosimetric and volumetric parameters were analyzed for their association with worst and last (W/L) toxicity outcomes. Results: Sixty-two patients had a minimum of 36 months of toxicity follow-up (median follow-up, 4.8 years). The W/L incidence of poor-fair cosmesis, any telangiectasia, and grade {>=}2 induration, volume reduction,more » and pain were 16.4%/11.5%, 24.2%/14.5%, 16.1%/9.7%, 17.7%/12.9%, and 11.3%/3.2%, respectively. Only the incidence of any telangiectasia was found to be predicted by any dosimetric parameter, with the absolute breast volume receiving 5% to 50% of the prescription dose (192.5 cGy-1925 cGy) being significant. No associations with maximum dose, volumes of lumpectomy cavity, breast, modified planning target volume, and PTV, dose homogeneity index, number of fields, and photon energy used were identified with any of the aforementioned toxicities. Non-upper outer quadrant location was associated with grade {>=}2 volume reduction (p = 0.02 W/p = 0.04 L). A small cavity-to-skin distance was associated with a grade {>=}2 induration (p = 0.03 W/p = 0.01 L), a borderline significant association with grade {>=}2 volume reduction (p = 0.06 W/p = 0.06 L) and poor-fair cosmesis (p = 0.08 W/p = 0.09 L), with threshold distances ranging from 5 to 8 mm. Conclusions: No dose--volume relationships associated with long-term toxicity were identified in this large patient cohort with extended follow-up. Cosmetic results were good-to-excellent in 88% of patients at 5 years.« less

Radiation dose delivered to the proximal penis as a predictor of the risk of erectile dysfunction after three-dimensional conformal radiotherapy for localized prostate cancer

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

Wernicke, A. Gabriella; Valicenti, Richard; DiEva, Kelly

2004-12-01

Purpose/objective: In this study, we evaluated in a serial manner whether radiation dose to the bulb of the penis is predictive of erectile dysfunction, ejaculatory difficulty (EJ), and overall satisfaction with sex life (quality of life) by using serial validated self-administered questionnaires. Methods and materials: Twenty-nine potent men with AJCC Stage II prostate cancer treated with three-dimensional conformal radiation therapy alone to a median dose 72.0 Gy (range: 66.6-79.2 Gy) were evaluated by determining the doses received by the penile bulb. The penile bulb was delineated volumetrically, and the dose-volume histogram was obtained on each patient. Results: The median follow-upmore » time was 35 months (range, 16-43 months). We found that for D{sub 30}, D{sub 45}, D{sub 60}, and D{sub 75} (doses to a percent volume of PB: 30%, 45%, 60%, and 75%), higher than the corresponding median dose (defined as high-dose group) correlated with an increased risk of impotence (erectile dysfunction firmness score = 0) (odds ratio [OR] = 7.5, p = 0.02; OR = 7.5, p = 0.02; OR = 8.6, p = 0.008; and OR = 6.9, p = 0.015, respectively). Similarly, for EJD D{sub 30}, D{sub 45}, D{sub 60}, and D{sub 75}, doses higher than the corresponding median ones correlated with worsening ejaculatory function score (EJ = 0 or 1) (OR = 8, p = 0.013; OR = 8, p 0.013; OR = 9.2, p = 0.015; and OR = 8, p = 0.026, respectively). For quality of life, low ({<=}median dose) dose groups of patients improve over time, whereas high-dose groups of patients worsen. Conclusions: This study supports the existence of a penile bulb dose-volume relationship underlying the development of radiation-induced erectile dysfunction. Our data may guide the use of inverse treatment planning to maximize the probability of maintaining sexual potency after radiation therapy.« less

Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost–IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate

PubMed Central

Bansal, A.; Kapoor, R.; Singh, S. K.; Kumar, N.; Oinam, A. S.; Sharma, S. C.

2012-01-01

Aims: Dosimeteric and radiobiological comparison of two radiation schedules in localized carcinoma prostate: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT). Material and Methods: Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose–volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared. Results: The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively. Conclusions: For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT. PMID:23204659

Adsorption of poly(ethylene succinate) chain onto graphene nanosheets: A molecular simulation.

PubMed

Kelich, Payam; Asadinezhad, Ahmad

2016-09-01

Understanding the interaction between single polymer chain and graphene nanosheets at local and global length scales is essential for it underlies the mesoscopic properties of polymer nanocomposites. A computational attempt was then performed using atomistic molecular dynamics simulation to gain physical insights into behavior of a model aliphatic polyester, poly(ethylene succinate), single chain near graphene nanosheets, where the effects of the polymer chain length, graphene functionalization, and temperature on conformational properties of the polymer were studied comparatively. Graphene functionalization was carried out through extending the parameters set of an all-atom force field. The results showed a significant conformational transition of the polymer chain from three-dimensional statistical coil, in initial state, to two-dimensional fold, in final state, during adsorption on graphene. The conformational order, overall shape, end-to-end separation statistics, and mobility of the polymer chain were found to be influenced by the graphene functionalization, temperature, and polymer chain length. Furthermore, the polymer chain dynamics mode during adsorption on graphene was observed to transit from normal diffusive to slow subdiffusive mode. The findings from this computational study could shed light on the physics of the early stages of aliphatic polyester chain organization induced by graphene. Copyright © 2016 Elsevier Inc. All rights reserved.

Supergravitational conformal Galileons

NASA Astrophysics Data System (ADS)

Deen, Rehan; Ovrut, Burt

2017-08-01

The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and "bouncing" cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory, but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios

Practical Methods for Including Torsional Anharmonicity in Thermochemical Calculations on Complex Molecules: The Internal-Coordinate Multi-Structural Approximation

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

Zheng, J.; Yu, T.; Papajak, E.

2011-01-01

Many methods for correcting harmonic partition functions for the presence of torsional motions employ some form of one-dimensional torsional treatment to replace the harmonic contribution of a specific normal mode. However, torsions are often strongly coupled to other degrees of freedom, especially other torsions and low-frequency bending motions, and this coupling can make assigning torsions to specific normal modes problematic. Here, we present a new class of methods, called multi-structural (MS) methods, that circumvents the need for such assignments by instead adjusting the harmonic results by torsional correction factors that are determined using internal coordinates. We present three versions ofmore » the MS method: (i) MS-AS based on including all structures (AS), i.e., all conformers generated by internal rotations; (ii) MS-ASCB based on all structures augmented with explicit conformational barrier (CB) information, i.e., including explicit calculations of all barrier heights for internal-rotation barriers between the conformers; and (iii) MS-RS based on including all conformers generated from a reference structure (RS) by independent torsions. In the MS-AS scheme, one has two options for obtaining the local periodicity parameters, one based on consideration of the nearly separable limit and one based on strongly coupled torsions. The latter involves assigning the local periodicities on the basis of Voronoi volumes. The methods are illustrated with calculations for ethanol, 1-butanol, and 1-pentyl radical as well as two one-dimensional torsional potentials. The MS-AS method is particularly interesting because it does not require any information about conformational barriers or about the paths that connect the various structures.« less

Practical methods for including torsional anharmonicity in thermochemical calculations on complex molecules: the internal-coordinate multi-structural approximation.

PubMed

Zheng, Jingjing; Yu, Tao; Papajak, Ewa; Alecu, I M; Mielke, Steven L; Truhlar, Donald G

2011-06-21

Many methods for correcting harmonic partition functions for the presence of torsional motions employ some form of one-dimensional torsional treatment to replace the harmonic contribution of a specific normal mode. However, torsions are often strongly coupled to other degrees of freedom, especially other torsions and low-frequency bending motions, and this coupling can make assigning torsions to specific normal modes problematic. Here, we present a new class of methods, called multi-structural (MS) methods, that circumvents the need for such assignments by instead adjusting the harmonic results by torsional correction factors that are determined using internal coordinates. We present three versions of the MS method: (i) MS-AS based on including all structures (AS), i.e., all conformers generated by internal rotations; (ii) MS-ASCB based on all structures augmented with explicit conformational barrier (CB) information, i.e., including explicit calculations of all barrier heights for internal-rotation barriers between the conformers; and (iii) MS-RS based on including all conformers generated from a reference structure (RS) by independent torsions. In the MS-AS scheme, one has two options for obtaining the local periodicity parameters, one based on consideration of the nearly separable limit and one based on strongly coupled torsions. The latter involves assigning the local periodicities on the basis of Voronoi volumes. The methods are illustrated with calculations for ethanol, 1-butanol, and 1-pentyl radical as well as two one-dimensional torsional potentials. The MS-AS method is particularly interesting because it does not require any information about conformational barriers or about the paths that connect the various structures.

Heat Shock Protein Genes Undergo Dynamic Alteration in Their Three-Dimensional Structure and Genome Organization in Response to Thermal Stress

PubMed Central

Chowdhary, Surabhi; Kainth, Amoldeep S.

2017-01-01

ABSTRACT Three-dimensional (3D) chromatin organization is important for proper gene regulation, yet how the genome is remodeled in response to stress is largely unknown. Here, we use a highly sensitive version of chromosome conformation capture in combination with fluorescence microscopy to investigate Heat Shock Protein (HSP) gene conformation and 3D nuclear organization in budding yeast. In response to acute thermal stress, HSP genes undergo intense intragenic folding interactions that go well beyond 5′-3′ gene looping previously described for RNA polymerase II genes. These interactions include looping between upstream activation sequence (UAS) and promoter elements, promoter and terminator regions, and regulatory and coding regions (gene “crumpling”). They are also dynamic, being prominent within 60 s, peaking within 2.5 min, and attenuating within 30 min, and correlate with HSP gene transcriptional activity. With similarly striking kinetics, activated HSP genes, both chromosomally linked and unlinked, coalesce into discrete intranuclear foci. Constitutively transcribed genes also loop and crumple yet fail to coalesce. Notably, a missense mutation in transcription factor TFIIB suppresses gene looping, yet neither crumpling nor HSP gene coalescence is affected. An inactivating promoter mutation, in contrast, obviates all three. Our results provide evidence for widespread, transcription-associated gene crumpling and demonstrate the de novo assembly and disassembly of HSP gene foci. PMID:28970326

Heat Shock Protein Genes Undergo Dynamic Alteration in Their Three-Dimensional Structure and Genome Organization in Response to Thermal Stress.

PubMed

Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2017-12-15

Three-dimensional (3D) chromatin organization is important for proper gene regulation, yet how the genome is remodeled in response to stress is largely unknown. Here, we use a highly sensitive version of chromosome conformation capture in combination with fluorescence microscopy to investigate Heat Shock Protein ( HSP ) gene conformation and 3D nuclear organization in budding yeast. In response to acute thermal stress, HSP genes undergo intense intragenic folding interactions that go well beyond 5'-3' gene looping previously described for RNA polymerase II genes. These interactions include looping between upstream activation sequence (UAS) and promoter elements, promoter and terminator regions, and regulatory and coding regions (gene "crumpling"). They are also dynamic, being prominent within 60 s, peaking within 2.5 min, and attenuating within 30 min, and correlate with HSP gene transcriptional activity. With similarly striking kinetics, activated HSP genes, both chromosomally linked and unlinked, coalesce into discrete intranuclear foci. Constitutively transcribed genes also loop and crumple yet fail to coalesce. Notably, a missense mutation in transcription factor TFIIB suppresses gene looping, yet neither crumpling nor HSP gene coalescence is affected. An inactivating promoter mutation, in contrast, obviates all three. Our results provide evidence for widespread, transcription-associated gene crumpling and demonstrate the de novo assembly and disassembly of HSP gene foci. Copyright © 2017 American Society for Microbiology.

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

NASA Astrophysics Data System (ADS)

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.

Crystal structure of 1,2,3,4-di-O-methyl­ene-α-d-galacto­pyran­ose

PubMed Central

Tiritiris, Ioannis; Tussetschläger, Stefan; Kantlehner, Willi

2015-01-01

The title compound, C8H12O6, was synthesized by de­acetyl­ation of 6-acetyl-1,2,3,4-di-O-methyl­ene-α-d-galactose with sodium methoxide. The central part of the mol­ecule consists of a six-membered C5O pyran­ose ring with a twist-boat conformation. Both fused dioxolane rings adopt an envelope conformation with C and O atoms as the flap. In the crystal, O—H⋯O and C—H⋯O hydrogen bonds are present between adjacent mol­ecules, generating a three-dimensional network. PMID:26870551

High dose bystander effects in spatially fractionated radiation therapy

PubMed Central

Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

2014-01-01

Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

Rapid Optimal SPH Particle Distributions in Spherical Geometries For Creating Astrophysical Initial Conditions

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

Raskin, Cody; Owen, J. Michael

Creating spherical initial conditions in smoothed particle hydrodynamics simulations that are spherically conformal is a difficult task. Here in this paper, we describe two algorithmic methods for evenly distributing points on surfaces that when paired can be used to build three-dimensional spherical objects with optimal equipartition of volume between particles, commensurate with an arbitrary radial density function. We demonstrate the efficacy of our method against stretched lattice arrangements on the metrics of hydrodynamic stability, spherical conformity, and the harmonic power distribution of gravitational settling oscillations. We further demonstrate how our method is highly optimized for simulating multi-material spheres, such asmore » planets with core–mantle boundaries.« less

Rapid Optimal SPH Particle Distributions in Spherical Geometries For Creating Astrophysical Initial Conditions

DOE PAGES

Raskin, Cody; Owen, J. Michael

2016-03-24

Creating spherical initial conditions in smoothed particle hydrodynamics simulations that are spherically conformal is a difficult task. Here in this paper, we describe two algorithmic methods for evenly distributing points on surfaces that when paired can be used to build three-dimensional spherical objects with optimal equipartition of volume between particles, commensurate with an arbitrary radial density function. We demonstrate the efficacy of our method against stretched lattice arrangements on the metrics of hydrodynamic stability, spherical conformity, and the harmonic power distribution of gravitational settling oscillations. We further demonstrate how our method is highly optimized for simulating multi-material spheres, such asmore » planets with core–mantle boundaries.« less

RAPID OPTIMAL SPH PARTICLE DISTRIBUTIONS IN SPHERICAL GEOMETRIES FOR CREATING ASTROPHYSICAL INITIAL CONDITIONS

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

Raskin, Cody; Owen, J. Michael

2016-04-01

Creating spherical initial conditions in smoothed particle hydrodynamics simulations that are spherically conformal is a difficult task. Here, we describe two algorithmic methods for evenly distributing points on surfaces that when paired can be used to build three-dimensional spherical objects with optimal equipartition of volume between particles, commensurate with an arbitrary radial density function. We demonstrate the efficacy of our method against stretched lattice arrangements on the metrics of hydrodynamic stability, spherical conformity, and the harmonic power distribution of gravitational settling oscillations. We further demonstrate how our method is highly optimized for simulating multi-material spheres, such as planets with core–mantlemore » boundaries.« less

New Insights into the Folding of a β-Sheet Miniprotein in a Reduced Space of Collective Hydrogen Bond Variables: Application to a Hydrodynamic Analysis of the Folding Flow

PubMed Central

Kalgin, Igor V.; Caflisch, Amedeo; Chekmarev, Sergei F.; Karplus, Martin

2013-01-01

A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted Principal Component Analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed and it is complemented by a hydrodynamic analysis. The latter, making use of “passive tracers” in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface, but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance in the hydrogen bond subspace. Comparison with the many published studies shows good agreement with the present analysis for the parts that can be compared, supporting the robust character of our understanding of this “hydrogen atom” of protein folding. PMID:23621790

X-ray diffraction studies of enkephalins. Crystal structure of [(4'-bromo) Phe4,Leu5]enkephalin.

PubMed Central

Ishida, T; Kenmotsu, M; Mino, Y; Inoue, M; Fujiwara, T; Tomita, K; Kimura, T; Sakakibara, S

1984-01-01

In order to investigate the structure-activity relationship of [Leu5]- and [Met5]enkephalins, [(4'-bromo)Phe4, Leu5]-, [(4'-bromo)Phe4, Met5]- and [Met5] enkephalins were synthesized and crystallized. The crystal structure of [(4'-bromo) Phe4, Leu5]- enkephalin was determined by X-ray diffraction method using the heavy atom method and refined to R = 0.092 by the least-squares method. The molecule in this crystal took essentially the same type I' beta-turn conformation found in [Leu5]enkephalin [Smith & Griffin (1978) Science 199, 1214-1216). On the other hand, the preliminary three-dimensional Patterson analyses showed that the most probable conformations of [(4'-bromo)Phe4,Met5]- and [Met5]enkephalins are both the dimeric extended forms. Based on these insights, the biologically active conformation of enkephalin was discussed in relation to the mu- and delta-receptors. PMID:6721829

Engineering the entropy-driven free-energy landscape of a dynamic nanoporous protein assembly.

PubMed

Alberstein, Robert; Suzuki, Yuta; Paesani, Francesco; Tezcan, F Akif

2018-04-30

De novo design and construction of stimuli-responsive protein assemblies that predictably switch between discrete conformational states remains an essential but highly challenging goal in biomolecular design. We previously reported synthetic, two-dimensional protein lattices self-assembled via disulfide bonding interactions, which endows them with a unique capacity to undergo coherent conformational changes without losing crystalline order. Here, we carried out all-atom molecular dynamics simulations to map the free-energy landscape of these lattices, validated this landscape through extensive structural characterization by electron microscopy and established that it is predominantly governed by solvent reorganization entropy. Subsequent redesign of the protein surface with conditionally repulsive electrostatic interactions enabled us to predictably perturb the free-energy landscape and obtain a new protein lattice whose conformational dynamics can be chemically and mechanically toggled between three different states with varying porosities and molecular densities.

High resolution approach to the native state ensemble kinetics and thermodynamics.

PubMed

Wu, Sangwook; Zhuravlev, Pavel I; Papoian, Garegin A

2008-12-15

Many biologically interesting functions such as allosteric switching or protein-ligand binding are determined by the kinetics and mechanisms of transitions between various conformational substates of the native basin of globular proteins. To advance our understanding of these processes, we constructed a two-dimensional free energy surface (FES) of the native basin of a small globular protein, Trp-cage. The corresponding order parameters were defined using two native substructures of Trp-cage. These calculations were based on extensive explicit water all-atom molecular dynamics simulations. Using the obtained two-dimensional FES, we studied the transition kinetics between two Trp-cage conformations, finding that switching process shows a borderline behavior between diffusive and weakly-activated dynamics. The transition is well-characterized kinetically as a biexponential process. We also introduced a new one-dimensional reaction coordinate for the conformational transition, finding reasonable qualitative agreement with the two-dimensional kinetics results. We investigated the distribution of all the 38 native nuclear magnetic resonance structures on the obtained FES, analyzing interactions that stabilize specific low-energy conformations. Finally, we constructed a FES for the same system but with simple dielectric model of water instead of explicit water, finding that the results were surprisingly similar in a small region centered on the native conformations. The dissimilarities between the explicit and implicit model on the larger-scale point to the important role of water in mediating interactions between amino acid residues.

Euclidean sections of protein conformation space and their implications in dimensionality reduction

PubMed Central

Duan, Mojie; Li, Minghai; Han, Li; Huo, Shuanghong

2014-01-01

Dimensionality reduction is widely used in searching for the intrinsic reaction coordinates for protein conformational changes. We find the dimensionality–reduction methods using the pairwise root–mean–square deviation as the local distance metric face a challenge. We use Isomap as an example to illustrate the problem. We believe that there is an implied assumption for the dimensionality–reduction approaches that aim to preserve the geometric relations between the objects: both the original space and the reduced space have the same kind of geometry, such as Euclidean geometry vs. Euclidean geometry or spherical geometry vs. spherical geometry. When the protein free energy landscape is mapped onto a 2D plane or 3D space, the reduced space is Euclidean, thus the original space should also be Euclidean. For a protein with N atoms, its conformation space is a subset of the 3N-dimensional Euclidean space R3N. We formally define the protein conformation space as the quotient space of R3N by the equivalence relation of rigid motions. Whether the quotient space is Euclidean or not depends on how it is parameterized. When the pairwise root–mean–square deviation is employed as the local distance metric, implicit representations are used for the protein conformation space, leading to no direct correspondence to a Euclidean set. We have demonstrated that an explicit Euclidean-based representation of protein conformation space and the local distance metric associated to it improve the quality of dimensionality reduction in the tetra-peptide and β–hairpin systems. PMID:24913095

Conformal field theory out of equilibrium: a review

NASA Astrophysics Data System (ADS)

Bernard, Denis; Doyon, Benjamin

2016-06-01

We provide a pedagogical review of the main ideas and results in non-equilibrium conformal field theory and connected subjects. These concern the understanding of quantum transport and its statistics at and near critical points. Starting with phenomenological considerations, we explain the general framework, illustrated by the example of the Heisenberg quantum chain. We then introduce the main concepts underlying conformal field theory (CFT), the emergence of critical ballistic transport, and the CFT scattering construction of non-equilibrium steady states. Using this we review the theory for energy transport in homogeneous one-dimensional critical systems, including the complete description of its large deviations and the resulting (extended) fluctuation relations. We generalize some of these ideas to one-dimensional critical charge transport and to the presence of defects, as well as beyond one-dimensional criticality. We describe non-equilibrium transport in free-particle models, where connections are made with generalized Gibbs ensembles, and in higher-dimensional and non-integrable quantum field theories, where the use of the powerful hydrodynamic ideas for non-equilibrium steady states is explained. We finish with a list of open questions. The review does not assume any advanced prior knowledge of conformal field theory, large-deviation theory or hydrodynamics.

Study on the interaction between cinnamic acid and lysozyme

NASA Astrophysics Data System (ADS)

Zhang, Hong-Mei; Chen, Jian; Zhou, Qiu-Hua; Shi, Yue-Qin; Wang, Yan-Qing

2011-02-01

The interaction between lysozyme and cinnamic acid was investigated systematically by ultraviolet-vis absorbance, circular dichroism, fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques at pH 7.40. The binding constants, quenching mechanism, and the number of binding sites were determined by the quenching of lysozyme fluorescence in presence of cinnamic acid. The results showed that the fluorescence quenching of lysozyme by cinnamic acid was a result of the formation of cinnamic acid-lysozyme complex. The hydrophobic and electrostatic interactions played major roles in stabilizing the complex; the distance r between donor and acceptor was obtained to be 2.07 nm according to Förster's theory; the effect of cinnamic acid on the conformation of lysozyme was analyzed using synchronous fluorescence, circular dichroism and three-dimensional fluorescence spectra.

3DSDSCAR--a three dimensional structural database for sialic acid-containing carbohydrates through molecular dynamics simulation.

PubMed

Veluraja, Kasinadar; Selvin, Jeyasigamani F A; Venkateshwari, Selvakumar; Priyadarzini, Thanu R K

2010-09-23

The inherent flexibility and lack of strong intramolecular interactions of oligosaccharides demand the use of theoretical methods for their structural elucidation. In spite of the developments of theoretical methods, not much research on glycoinformatics is done so far when compared to bioinformatics research on proteins and nucleic acids. We have developed three dimensional structural database for a sialic acid-containing carbohydrates (3DSDSCAR). This is an open-access database that provides 3D structural models of a given sialic acid-containing carbohydrate. At present, 3DSDSCAR contains 60 conformational models, belonging to 14 different sialic acid-containing carbohydrates, deduced through 10 ns molecular dynamics (MD) simulations. The database is available at the URL: http://www.3dsdscar.org. Copyright 2010 Elsevier Ltd. All rights reserved.

Three-dimensional aromatic networks.

PubMed

Toyota, Shinji; Iwanaga, Tetsuo

2014-01-01

Three-dimensional (3D) networks consisting of aromatic units and linkers are reviewed from various aspects. To understand principles for the construction of such compounds, we generalize the roles of building units, the synthetic approaches, and the classification of networks. As fundamental compounds, cyclophanes with large aromatic units and aromatic macrocycles with linear acetylene linkers are highlighted in terms of transannular interactions between aromatic units, conformational preference, and resolution of chiral derivatives. Polycyclic cage compounds are constructed from building units by linkages via covalent bonds, metal-coordination bonds, or hydrogen bonds. Large cage networks often include a wide range of guest species in their cavity to afford novel inclusion compounds. Topological isomers consisting of two or more macrocycles are formed by cyclization of preorganized species. Some complicated topological networks are constructed by self-assembly of simple building units.

Large Bone Vertical Augmentation Using a Three-Dimensional Printed TCP/HA Bone Graft: A Pilot Study in Dog Mandible.

PubMed

Carrel, Jean-Pierre; Wiskott, Anselm; Scherrer, Susanne; Durual, Stéphane

2016-12-01

Osteoflux is a three-dimensional printed calcium phosphate porous structure for oral bone augmentation. It is a mechanically stable scaffold with a well-defined interconnectivity and can be readily shaped to conform to the bone bed's morphology. An animal experiment is reported whose aim was to assess the performance and safety of the scaffold in promoting vertical growth of cortical bone in the mandible. Four three-dimensional blocks (10 mm length, 5 mm width, 5 mm height) were affixed to edentulous segments of the dog's mandible and covered by a collagen membrane. During bone bed preparation, particular attention was paid not to create defects 0.5 mm or more so that the real potential of the three-dimensional block in driving vertical bone growth can be assessed. Histomorphometric analyses were performed after 8 weeks. At 8 weeks, the three-dimensional blocks led to substantial vertical bone growth up to 4.5 mm from the bone bed. Between 0 and 1 mm in height, 44% of the surface was filled with new bone, at 1 to 3 mm it was 20% to 35%, 18% at 3 to 4, and ca. 6% beyond 4 mm. New bone was evenly distributed along in mesio-distal direction and formed a new crest contour in harmony with the natural mandibular shape. After two months of healing, the three-dimensional printed blocks conducted new bone growth above its natural bed, up to 4.5 mm in a canine mandibular model. Furthermore, the new bone was evenly distributed in height and density along the block. These results are very promising and need to be further evaluated by a complete powerful study using the same model. © 2016 Wiley Periodicals, Inc.

From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction.

PubMed

Akhter, Nasrin; Shehu, Amarda

2018-01-19

Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

Dosimetric comparison between conventional and conformal radiotherapy for carcinoma cervix: Are we treating the right volumes?

PubMed Central

Goswami, Jyotirup; Patra, Niladri B.; Sarkar, Biplab; Basu, Ayan; Pal, Santanu

2013-01-01

Background and Purpose: Conventional portals, based on bony anatomy, for external beam radiotherapy for cervical cancer have been repeatedly demonstrated as inadequate. Conversely, with image-based conformal radiotherapy, better target coverage may be offset by the greater toxicities and poorer compliance associated with treating larger volumes. This study was meant to dosimetrically compare conformal and conventional radiotherapy. Materials and Methods: Five patients of carcinoma cervix underwent planning CT scan with IV contrast and targets, and organs at risk (OAR) were contoured. Two sets of plans-conventional and conformal were generated for each patient. Field sizes were recorded, and dose volume histograms of both sets of plans were generated and compared on the basis of target coverage and OAR sparing. Results: Target coverage was significantly improved with conformal plans though field sizes required were significantly larger. On the other hand, dose homogeneity was not significantly improved. Doses to the OARs (rectum, urinary bladder, and small bowel) were not significantly different across the 2 arms. Conclusion: Three-dimensional conformal radiotherapy gives significantly better target coverage, which may translate into better local control and survival. On the other hand, it also requires significantly larger field sizes though doses to the OARs are not significantly increased. PMID:24455584

Meta-analysis of incidence of early lung toxicity in 3-dimensional conformal irradiation of breast carcinomas

PubMed Central

2013-01-01

Background This meta-analysis aims to ascertain the significance of early lung toxicity with 3-Dimensional (3D) conformal irradiation for breast carcinomas and identify the sub-groups of patients with increased risk. Methods Electronic databases, reference sections of major oncological textbooks and identified studies were searched for synonyms of breast radiotherapy and radiation pneumonitis (RP). Major studies in thoracic irradiation were reviewed to identify factors frequently associated with RP. Meta-analysis for RP incidence estimation and odds ratio calculation were carried out. Results The overall incidence of Clinical and Radiological RP is 14% and 42% respectively. Ten studies were identified. Dose-volume Histogram (DVH) related dosimetric factors (Volume of lung receiving certain dose, Vdose and Mean lung Dose, MLD), supraclavicular fossa (SCF) irradiation and age are significantly associated with RP, but not sequential chemotherapy and concomitant use of Tamoxifen. A poorly powered study in IMN group contributed to the negative finding. Smoking has a trend towards protective effect against RP. Conclusion Use of other modalities may be considered when Ipsilateral lung V20Gy > 30% or MLD > 15 Gy. Extra caution is needed in SCF and IMN irradiation as they are likely to influence these dosimetric parameters. PMID:24229418

A VLSI implementation for synthetic aperture radar image processing

NASA Technical Reports Server (NTRS)

Premkumar, A.; Purviance, J.

1990-01-01

A simple physical model for the Synthetic Aperture Radar (SAR) is presented. This model explains the one dimensional and two dimensional nature of the received SAR signal in the range and azimuth directions. A time domain correlator, its algorithm, and features are explained. The correlator is ideally suited for VLSI implementation. A real time SAR architecture using these correlators is proposed. In the proposed architecture, the received SAR data is processed using one dimensional correlators for determining the range while two dimensional correlators are used to determine the azimuth of a target. The architecture uses only three different types of custom VLSI chips and a small amount of memory.

Protein Misfolding Diseases.

PubMed

Hartl, F Ulrich

2017-06-20

The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies. To prevent or regulate protein aggregation, all cells contain an extensive protein homeostasis (or proteostasis) network comprising molecular chaperones and other factors. These defense systems tend to decline during aging, facilitating the manifestation of aggregate deposition diseases. This volume of the Annual Review of Biochemistry contains a set of three articles addressing our current understanding of the structures of pathological protein aggregates and their associated disease mechanisms. These articles also discuss recent insights into the strategies cells have evolved to neutralize toxic aggregates by sequestering them in specific cellular locations.

High-resolution three-dimensional imaging radar

NASA Technical Reports Server (NTRS)

Cooper, Ken B. (Inventor); Chattopadhyay, Goutam (Inventor); Siegel, Peter H. (Inventor); Dengler, Robert J. (Inventor); Schlecht, Erich T. (Inventor); Mehdi, Imran (Inventor); Skalare, Anders J. (Inventor)

2010-01-01

A three-dimensional imaging radar operating at high frequency e.g., 670 GHz, is disclosed. The active target illumination inherent in radar solves the problem of low signal power and narrow-band detection by using submillimeter heterodyne mixer receivers. A submillimeter imaging radar may use low phase-noise synthesizers and a fast chirper to generate a frequency-modulated continuous-wave (FMCW) waveform. Three-dimensional images are generated through range information derived for each pixel scanned over a target. A peak finding algorithm may be used in processing for each pixel to differentiate material layers of the target. Improved focusing is achieved through a compensation signal sampled from a point source calibration target and applied to received signals from active targets prior to FFT-based range compression to extract and display high-resolution target images. Such an imaging radar has particular application in detecting concealed weapons or contraband.

Implementation of three dimensional conformal radiation therapy: prospects, opportunities, and challenges.

PubMed

Vijayakumar, S; Chen, G T

1995-12-01

To briefly review scientific rationale of 3D conformal radiation therapy (3DCRT) and discuss the prospects, opportunities, and challenges in the implementation of 3DCRT. Some of these ideas were discussed during a workshop on "Implementation of Three-Dimensional Conformal Radiation Therapy" in April 1994 at Bethesda, MD, and others have been discussed elsewhere in the literature. Local-regional control of cancer is an important component in the overall treatment strategy in any patient with cancer. It has been shown that failure to achieve local-regional control can lead to (a) an increase in chances of distant metastases, and (b) a decrease in the survival. In many disease sites, the doses delivered currently are inadequate to achieve satisfactory local tumor control rates; this is because in many sites, only limited doses of radiotherapy can be delivered due to the proximity of cancer to radiosensitive normal tissues. By conforming the radiotherapy beams to the tumor, doses to the tumors can be enhanced and doses to the normal tissues can be reduced. With the advances in 3DCRT, such conformation is possible now and is the rationale for using 3DCRT. However, a number of questions do remain that are not limited to the following: (a) What are the implications in terms of target volume definitions when implementing 3DCRT? (b) Are there some sites where research efforts can be focused to document the efficacy and cost effectiveness of 3DCRT? (c) How do we implement day-to-day 3DCRT treatment efficiently? (d) How do we transfer the technology from the university centers to the community without compromising quality? (e) What are all the quality assurance/quality improvement questions that need to be addressed and how do we ascertain quality assurance of 3DCRT? (f) Have we looked at cost-benefit ratios and quality of life (QOL) issues closely? There is a need for defining multiple target volumes: gross tumor volume, clinical target volume(s), and planning target volume(s). Such definitions should make implementation of 3DCRT more complex, yet will make high-dose delivery a possibility. There are many sites in which single and multiinstitutional studies are ongoing that include prostate, lung, head and neck, and brain. In other areas, cooperative group trials are required because of the inability of single institutions to accrue enough patients to answer clinically relevant questions with statistical validity. Although implementation of 3DCRT will require multiple steps, these multiple steps can be brought into clinical practice gradually and one does not have to wait until all steps required for implementation of 3DCRT are available. In this respect, "3DCRT" should be used in a very broad sense, from beam's eye view blocking, use of multibeam dose distribution, use of dose-volume histograms in choosing alternative plans, noncoplanar beam arrangements, intensity modulation, inverse planning, to totally automated implementation of 3DCRT. To transfer the 3DCRT capabilities to the community from the University Centers, there is a necessity to develop quality assurance programs. RTOG and the Three-Dimensional Oncology Group are spearheading these efforts. Three-dimensional conformal radiation therapy has potential not only to improve local control and decrease toxicity, but also to improve the cost benefit ratio in the use of radiotherapy as well as in improving quality of life in patients with cancer. Achieving many potential benefits of 3DCRT (improvement in local control, decreasing toxicity, organs-function preservation, improvement in cost effectiveness) will require further physics-related and clinical research in carefully conceived and successfully completed future clinical trials.

Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor.

PubMed

Ingram, M; Techy, G B; Saroufeem, R; Yazan, O; Narayan, K S; Goodwin, T J; Spaulding, G F

1997-06-01

Growth patterns of a number of human tumor cell lines that from three-dimensional structures of various architectures when cultured without carrier beads in a NASA rotary cell culture system are described and illustrated. The culture system, which was designed to mimic microgravity, maintained cells in suspension under very low-shear stress throughout culture. Spheroid (particulate) production occurred within a few hours after culture was started, and spheroids increased in size by cell division and fusion of small spheroids, usually stabilizing at a spheroid diameter of about 0.5 mm. Architecture of spheroids varied with cell type. Cellular interactions that occurred in spheroids resulted in conformation and shape changes of cells, and some cell lines produced complex, epithelial-like architectures. Expression of the cell adhesion molecules, CD44 and E cadherin, was upregulated in the three-dimensional constructs. Coculture of fibroblast spheroids with PC3 prostate cancer cells induced tenascin expression by the fibroblasts underlying the adherent prostate epithelial cells. Invasion of the fibroblast spheroids by the malignant epithelium was also demonstrated.

Potential advantage of studying the lymphatic drainage by sentinel node technique and SPECT-CT image fusion for pelvic irradiation of prostate cancer

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

Krengli, Marco; Ballare, Andrea; Cannillo, Barbara

2006-11-15

Purpose: This study aims to investigate the in vivo drainage of lymphatic spread by using the sentinel node (SN) technique and single-photon emission computed tomography (SPECT)-computed tomography (CT) image fusion, and to analyze the impact of such information on conformal pelvic irradiation. Methods and Materials: Twenty-three prostate cancer patients, candidates for radical prostatectomy already included in a trial studying the SN technique, were enrolled. CT and SPECT images were obtained after intraprostate injection of 115 MBq of {sup 99m}Tc-nanocolloid, allowing identification of SN and other pelvic lymph nodes. Target and nontarget structures, including lymph nodes identified by SPECT, were drawnmore » on SPECT-CT fusion images. A three-dimensional conformal treatment plan was performed for each patient. Results: Single-photon emission computed tomography lymph nodal uptake was detected in 20 of 23 cases (87%). The SN was inside the pelvic clinical target volume (CTV{sub 2}) in 16 of 20 cases (80%) and received no less than the prescribed dose in 17 of 20 cases (85%). The most frequent locations of SN outside the CTV{sub 2} were the common iliac and presacral lymph nodes. Sixteen of the 32 other lymph nodes (50%) identified by SPECT were found outside the CTV{sub 2}. Overall, the SN and other intrapelvic lymph nodes identified by SPECT were not included in the CTV{sub 2} in 5 of 20 (25%) patients. Conclusions: The study of lymphatic drainage can contribute to a better knowledge of the in vivo potential pattern of lymph node metastasis in prostate cancer and can lead to a modification of treatment volume with consequent optimization of pelvic irradiation.« less

Homologous ligands accommodated by discrete conformations of a buried cavity

PubMed Central

Merski, Matthew; Fischer, Marcus; Balius, Trent E.; Eidam, Oliv; Shoichet, Brian K.

2015-01-01

Conformational change in protein–ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design. PMID:25847998

Homologous ligands accommodated by discrete conformations of a buried cavity.

PubMed

Merski, Matthew; Fischer, Marcus; Balius, Trent E; Eidam, Oliv; Shoichet, Brian K

2015-04-21

Conformational change in protein-ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design.

D-type conformal matter and SU/USp quivers

NASA Astrophysics Data System (ADS)

Kim, Hee-Cheol; Razamat, Shlomo S.; Vafa, Cumrun; Zafrir, Gabi

2018-06-01

We discuss the four dimensional models obtained by compactifying a single M5 brane probing D N singularity (minimal D-type (1 , 0) conformal matter in six dimensions) on a torus with flux for abelian subgroups of the SO(4 N) flavor symmetry. We derive the resulting quiver field theories in four dimensions by first compactifying on a circle and relating the flux to duality domain walls in five dimensions. This leads to novel N=1 dualities in 4 dimensions which arise from distinct five dimensional realizations of the circle compactifications of the D-type conformal matter.

Hidden conformal symmetry of rotating black holes in minimal five-dimensional gauged supergravity

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

Setare, M. R.; Kamali, V.

2010-10-15

In the present paper we show that for a low frequency limit the wave equation of a massless scalar field in the background of nonextremal charged rotating black holes in five-dimensional minimal gauged and ungauged supergravity can be written as the Casimir of an SL(2,R) symmetry. Our result shows that the entropy of the black hole is reproduced by the Cardy formula. Also the absorption cross section is consistent with the finite temperature absorption cross section for a two-dimensional conformal field theory.

Modelling of Time-Variant Flows Using Vortex Dynamics.

DTIC Science & Technology

1987-02-01

eopennage.... ) avec nappes enroul~es et d~ chir ~cs. REFERENCES Ji .T. BEALE, A. MAJDA "Nigh order accurate vortex methods with explicit velocity kernel...discrete vortices. Two papers, Longuet- Higgins (37) and Smith and Stansby (38) deal with the problem. In (37) conformal transformation is used for the...Longuet- Higgins (37). Most experiments on separated flows undoubtedly contain three-dimensional effects and again vortex decay is occasionally put into the

The three-dimensional structure of TrmB, a transcriptional regulator of dual function in the hyperthermophilic archaeon Pyrococcus furiosus in complex with sucrose

PubMed Central

Krug, Michael; Lee, Sung-Jae; Boos, Winfried; Diederichs, Kay; Welte, Wolfram

2013-01-01

TrmB is a repressor that binds maltose, maltotriose, and sucrose, as well as other α-glucosides. It recognizes two different operator sequences controlling the TM (Trehalose/Maltose) and the MD (Maltodextrin) operon encoding the respective ABC transporters and sugar-degrading enzymes. Binding of maltose to TrmB abrogates repression of the TM operon but maintains the repression of the MD operon. On the other hand, binding of sucrose abrogates repression of the MD operon but maintains repression of the TM operon. The three-dimensional structure of TrmB in complex with sucrose was solved and refined to a resolution of 3.0 Å. The structure shows the N-terminal DNA binding domain containing a winged-helix-turn-helix (wHTH) domain followed by an amphipathic helix with a coiled-coil motif. The latter promotes dimerization and places the symmetry mates of the putative recognition helix in the wHTH motif about 30 Å apart suggesting a canonical binding to two successive major grooves of duplex palindromic DNA. This suggests that the structure resembles the conformation of TrmB recognizing the pseudopalindromic TM promoter but not the conformation recognizing the nonpalindromic MD promoter. PMID:23576322

Chapter 5. Hidden Symmetry and Exact Solutions in Einstein Gravity

NASA Astrophysics Data System (ADS)

Yasui, Y.; Houri, T.

Conformal Killing-Yano tensors are introduced as ageneralization of Killing vectors. They describe symmetries of higher-dimensional rotating black holes. In particular, a rank-2 closed conformal Killing-Yano tensor generates the tower of both hidden symmetries and isometries. We review a classification of higher-dimensional spacetimes admitting such a tensor, and present exact solutions to the Einstein equations for these spacetimes.

Proper Conformal Killing Vectors in Kantowski-Sachs Metric

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Farhan, Muhammad

2018-04-01

This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.

Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments.

PubMed

Poltev, V; Anisimov, V M; Dominguez, V; Gonzalez, E; Deriabina, A; Garcia, D; Rivas, F; Polteva, N A

2018-02-01

Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.

Coarse-grained simulations of protein-protein association: an energy landscape perspective.

PubMed

Ravikumar, Krishnakumar M; Huang, Wei; Yang, Sichun

2012-08-22

Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

2D hybrid analysis: Approach for building three-dimensional atomic model by electron microscopy image matching.

PubMed

Matsumoto, Atsushi; Miyazaki, Naoyuki; Takagi, Junichi; Iwasaki, Kenji

2017-03-23

In this study, we develop an approach termed "2D hybrid analysis" for building atomic models by image matching from electron microscopy (EM) images of biological molecules. The key advantage is that it is applicable to flexible molecules, which are difficult to analyze by 3DEM approach. In the proposed approach, first, a lot of atomic models with different conformations are built by computer simulation. Then, simulated EM images are built from each atomic model. Finally, they are compared with the experimental EM image. Two kinds of models are used as simulated EM images: the negative stain model and the simple projection model. Although the former is more realistic, the latter is adopted to perform faster computations. The use of the negative stain model enables decomposition of the averaged EM images into multiple projection images, each of which originated from a different conformation or orientation. We apply this approach to the EM images of integrin to obtain the distribution of the conformations, from which the pathway of the conformational change of the protein is deduced.

Direct Growth of Graphene Films on 3D Grating Structural Quartz Substrates for High-Performance Pressure-Sensitive Sensors.

PubMed

Song, Xuefen; Sun, Tai; Yang, Jun; Yu, Leyong; Wei, Dacheng; Fang, Liang; Lu, Bin; Du, Chunlei; Wei, Dapeng

2016-07-06

Conformal graphene films have directly been synthesized on the surface of grating microstructured quartz substrates by a simple chemical vapor deposition process. The wonderful conformality and relatively high quality of the as-prepared graphene on the three-dimensional substrate have been verified by scanning electron microscopy and Raman spectra. This conformal graphene film possesses excellent electrical and optical properties with a sheet resistance of <2000 Ω·sq(-1) and a transmittance of >80% (at 550 nm), which can be attached with a flat graphene film on a poly(dimethylsiloxane) substrate, and then could work as a pressure-sensitive sensor. This device possesses a high-pressure sensitivity of -6.524 kPa(-1) in a low-pressure range of 0-200 Pa. Meanwhile, this pressure-sensitive sensor exhibits super-reliability (≥5000 cycles) and an ultrafast response time (≤4 ms). Owing to these features, this pressure-sensitive sensor based on 3D conformal graphene is adequately introduced to test wind pressure, expressing higher accuracy and a lower background noise level than a market anemometer.

Coarse-Grained Simulations of Protein-Protein Association: An Energy Landscape Perspective

PubMed Central

Ravikumar, Krishnakumar M.; Huang, Wei; Yang, Sichun

2012-01-01

Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes. PMID:22947945

Modeling Conformal Growth in Photonic Crystals and Comparing to Experiment

NASA Astrophysics Data System (ADS)

Brzezinski, Andrew; Chen, Ying-Chieh; Wiltzius, Pierre; Braun, Paul

2008-03-01

Conformal growth, e.g. atomic layer deposition (ALD), of materials such as silicon and TiO2 on three dimensional (3D) templates is important for making photonic crystals. However, reliable calculations of optical properties as a function of the conformal growth, such as the optical band structure, are hampered by difficultly in accurately assessing a deposited material's spatial distribution. A widely used approximation ignores ``pinch off'' of precursor gas and assumes complete template infilling. Another approximation results in non-uniform growth velocity by employing iso-intensity surfaces of the 3D interference pattern used to create the template. We have developed an accurate model of conformal growth in arbitrary 3D periodic structures, allowing for arbitrary surface orientation. Results are compared with the above approximations and with experimentally fabricated photonic crystals. We use an SU8 polymer template created by 4-beam interference lithography, onto which various amounts of TiO2 are grown by ALD. Characterization is performed by analysis of cross-sectional scanning electron micrographs and by solid angle resolved optical spectroscopy.

Computational carbohydrate chemistry: what theoretical methods can tell us

PubMed Central

Woods, Robert J.

2014-01-01

Computational methods have had a long history of application to carbohydrate systems and their development in this regard is discussed. The conformational analysis of carbohydrates differs in several ways from that of other biomolecules. Many glycans appear to exhibit numerous conformations coexisting in solution at room temperature and a conformational analysis of a carbohydrate must address both spatial and temporal properties. When solution nuclear magnetic resonance data are used for comparison, the simulation must give rise to ensemble-averaged properties. In contrast, when comparing to experimental data obtained from crystal structures a simulation of a crystal lattice, rather than of an isolated molecule, is appropriate. Molecular dynamics simulations are well suited for such condensed phase modeling. Interactions between carbohydrates and other biological macromolecules are also amenable to computational approaches. Having obtained a three-dimensional structure of the receptor protein, it is possible to model with accuracy the conformation of the carbohydrate in the complex. An example of the application of free energy perturbation simulations to the prediction of carbohydrate-protein binding energies is presented. PMID:9579797

Three-Dimensional Direct Numerical Simulation of Methane-Air Turbulent Premixed Flames with Reduced Kinetic Mechanism

NASA Astrophysics Data System (ADS)

Tanahashi, Mamoru; Kikuta, Satoshi; Miyauchi, Toshio

2004-11-01

Three-dimensional DNS of methane-air turbulent premixed flames have been conducted to investigate local extinction mechanism of turbulent premixed flames. A reduced kinetic mechanism (MeCH-19), which is created from GRI-Mech. 2.11 and includes 23 reactive species and 19 step reactions, are used to simulate CH_4-O_2-N2 reaction in turbulence. The effectiveness of this reduced kinetic mechanism has been conformed by preliminary two-dimensional DNS with the reduced kinetic mechanism and two detailed kinetic mechanisms; GRI-Mech. 2.11 and Miller & Bowman. Flame structures of methane-air turbulent premixed flames are compared with those of hydrogen-air turbulent premixed flames which have been obtained by 3D-DNS with a detailed kinetic mechanism in our previous study. Local extinctions occur in methane-air turbulent premixed flames, whereas no extinction is observed for hydrogen-air flames in nearly same turbulence condition. The local extinction mechanism is discussed based on eddy/flame interaction in small scales.

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography

DOE PAGES

Lei, Dongsheng; Marras, Alexander E.; Liu, Jianfang; ...

2018-02-09

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. In this paper, we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~6-14 nm resolution. The statisticalmore » analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.« less

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography

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

Lei, Dongsheng; Marras, Alexander E.; Liu, Jianfang

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. In this paper, we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~6-14 nm resolution. The statisticalmore » analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.« less

External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

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

Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receivingmore » AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.« less

Late Toxicity and Patient Self-Assessment of Breast Appearance/Satisfaction on RTOG 0319: A Phase 2 Trial of 3-Dimensional Conformal Radiation Therapy-Accelerated Partial Breast Irradiation Following Lumpectomy for Stages I and II Breast Cancer

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

Chafe, Susan, E-mail: susan.chafe@albertahealthservices.ca; Moughan, Jennifer; McCormick, Beryl

2013-08-01

Purpose: Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials: Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adversemore » Events, version 3.0, was used to grade toxicity. Results: Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Conclusions: Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again.« less

Late toxicity and patient self-assessment of breast appearance/satisfaction on RTOG 0319: a phase 2 trial of 3-dimensional conformal radiation therapy-accelerated partial breast irradiation following lumpectomy for stages I and II breast cancer.

PubMed

Chafe, Susan; Moughan, Jennifer; McCormick, Beryl; Wong, John; Pass, Helen; Rabinovitch, Rachel; Arthur, Douglas W; Petersen, Ivy; White, Julia; Vicini, Frank A

2013-08-01

Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again. Copyright © 2013. Published by Elsevier Inc.

Inflation in Flatland

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

Hinterbichler, Kurt; Joyce, Austin; Khoury, Justin, E-mail: kurt.hinterbichler@case.edu, E-mail: austin.joyce@columbia.edu, E-mail: jkhoury@sas.upenn.edu

We investigate the symmetry structure of inflation in 2+1 dimensions. In particular, we show that the asymptotic symmetries of three-dimensional de Sitter space are in one-to-one correspondence with cosmological adiabatic modes for the curvature perturbation. In 2+1 dimensions, the asymptotic symmetry algebra is infinite-dimensional, given by two copies of the Virasoro algebra, and can be traced to the conformal symmetries of the two-dimensional spatial slices of de Sitter. We study the consequences of this infinite-dimensional symmetry for inflationary correlation functions, finding new soft theorems that hold only in 2+1 dimensions. Expanding the correlation functions as a power series in themore » soft momentum q , these relations constrain the traceless part of the tensorial coefficient at each order in q in terms of a lower-point function. As a check, we verify that the O( q {sup 2}) identity is satisfied by inflationary correlation functions in the limit of small sound speed.« less

z -Weyl gravity in higher dimensions

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

Moon, Taeyoon; Oh, Phillial, E-mail: dpproject@skku.edu, E-mail: ploh@skku.edu

We consider higher dimensional gravity in which the four dimensional spacetime and extra dimensions are not treated on an equal footing. The anisotropy is implemented in the ADM decomposition of higher dimensional metric by requiring the foliation preserving diffeomorphism invariance adapted to the extra dimensions, thus keeping the general covariance only for the four dimensional spacetime. The conformally invariant gravity can be constructed with an extra (Weyl) scalar field and a real parameter z which describes the degree of anisotropy of conformal transformation between the spacetime and extra dimensional metrics. In the zero mode effective 4D action, it reduces tomore » four-dimensional scalar-tensor theory coupled with nonlinear sigma model described by extra dimensional metrics. There are no restrictions on the value of z at the classical level and possible applications to the cosmological constant problem with a specific choice of z are discussed.« less

Treatment-Related Morbidity in Prostate Cancer: A Comparison of 3-Dimensional Conformal Radiation Therapy With and Without Image Guidance Using Implanted Fiducial Markers

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

Singh, Jasmeet, E-mail: drsingh.j@gmail.com; Greer, Peter B.; White, Martin A.

Purpose: To estimate the prevalence of rectal and urinary dysfunctional symptoms using image guided radiation therapy (IGRT) with fiducials and magnetic resonance planning for prostate cancer. Methods and Materials: During the implementation stages of IGRT between September 2008 and March 2010, 367 consecutive patients were treated with prostatic irradiation using 3-dimensional conformal radiation therapy with and without IGRT (non-IGRT). In November 2010, these men were asked to report their bowel and bladder symptoms using a postal questionnaire. The proportions of patients with moderate to severe symptoms in these groups were compared using logistic regression models adjusted for tumor and treatmentmore » characteristic variables. Results: Of the 282 respondents, the 154 selected for IGRT had higher stage tumors, received higher prescribed doses, and had larger volumes of rectum receiving high dosage than did the 128 selected for non-IGRT. The follow-up duration was 8 to 26 months. Compared with the non-IGRT group, improvement was noted in all dysfunctional rectal symptoms using IGRT. In multivariable analyses, IGRT improved rectal pain (odds ratio [OR] 0.07 [0.009-0.7], P=.02), urgency (OR 0.27 [0.11-0.63], P=<.01), diarrhea (OR 0.009 [0.02-0.35], P<.01), and change in bowel habits (OR 0.18 [0.06-0.52], P<.010). No correlation was observed between rectal symptom levels and dose-volume histogram data. Urinary dysfunctional symptoms were similar in both treatment groups. Conclusions: In comparison with men selected for non-IGRT, a significant reduction of bowel dysfunctional symptoms was confirmed in men selected for IGRT, even though they had larger volumes of rectum treated to higher doses.« less

A new Gamma Knife registered radiosurgery paradigm: Tomosurgery

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

Hu, X.; Maciunas, R. J.; Dean, D.

This study proposes and simulates an inverse treatment planning and a continuous dose delivery approach for the Leksell Gamma Knife registered (LGK, Elekta, Stockholm, Sweden) which we refer to as 'Tomosurgery'. Tomosurgery uses an isocenter that moves within the irradiation field to continuously deliver the prescribed radiation dose in a raster-scanning format, slice by slice, within an intracranial lesion. Our Tomosurgery automated (inverse) treatment planning algorithm utilizes a two-stage optimization strategy. The first stage reduces the current three-dimensional (3D) treatment planning problem to a series of more easily solved 2D treatment planning subproblems. In the second stage, those 2D treatmentmore » plans are assembled to obtain a final 3D treatment plan for the entire lesion. We created Tomosurgery treatment plans for 11 patients who had already received manually-generated LGK treatment plans to treat brain tumors. For the seven cases without critical structures (CS), the Tomosurgery treatment plans showed borderline to significant improvement in within-tumor dose standard deviation (STD) (p<0.058, or p<0.011 excluding case 2) and conformality (p<0.042), respectively. In three of the four cases that presented CS, the Tomosurgery treatment plans showed no statistically significant improvements in dose conformality (p<0.184), and borderline significance in improving within-tumor dose homogeneity (p<0.054); CS damage measured by V{sub 20} or V{sub 30} (i.e., irradiated CS volume that receives {>=}20% or {>=}30% of the maximum dose) showed no significant improvement in the Tomosurgery treatment plans (p<0.345 and p<0.423, respectively). However, the overall CS dose volume histograms were improved in the Tomosurgery treatment plans. In addition, the LGK Tomosurgery inverse treatment planning required less time than standard of care, forward (manual) LGK treatment planning (i.e., 5-35 min vs 1-3 h) for all 11 cases. We expect that LGK Tomosurgery will speed treatment planning and improve treatment quality, especially for large and/or geometrically complex lesions. However, using only 4 mm collimators could greatly increase treatment plan delivery time for a large brain lesion. This issue is subject to further investigation.« less

Radiation-induced Liver Injury after 3D-conformal Radiotherapy for Hepatocellular Carcinoma: Quantitative Assessment Using Gd-EOB-DTPA-enhanced MRI.

PubMed

Fukugawa, Yoshiyuki; Namimoto, Tomohiro; Toya, Ryo; Saito, Tetsuo; Yuki, Hideaki; Matsuyama, Tomohiko; Ikeda, Osamu; Yamashita, Yasuyuki; Oya, Natsuo

2017-02-01

Focal liver reaction (FLR) appears in the hepatobiliary-phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) following radiotherapy (RT). We investigated the threshold dose (TD) for FLR development in 13 patients with hepatocellular carcinoma (HCC) who underwent three-dimensional conformal radiotherapy (3D-CRT) with 45 Gy in 15 fractions. FLR volumes (FLRVs) were calculated based on planning CT images by referring to fused hepatobiliary- phase images. We also calculated the TD and the irradiated volumes (IVs) of the liver parenchyma at a given dose of every 5 Gy (IVdose) based on a dose-volume histogram (DVH). The median TD was 35.2 Gy. The median IV20, IV25, IV30, IV35, IV40, and IV45 values were 371.1, 274.8, 233.4, 188.6, 145.8, and 31.0 ml, respectively. The median FLRV was 144.9 ml. There was a significant difference between the FLRV and IV20, IV25, and IV45 (p<0.05), but no significant differences between the FLRV and IV30, IV35, or IV40. These results suggest that the threshold dose of the FLR is approx. 35 Gy in HCC patients who undergo 3D-CRT in 15 fractions. The percentage of the whole liver volume receiving a dose of more than 30-40 Gy (V30-40) is a potential candidate optimal DVH parameter for this fractionation schedule.

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

NASA Astrophysics Data System (ADS)

Shute, Richard E.; Jackson, David E.; Bycroft, Barrie W.

1989-06-01

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic β-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3 R-compounds possess notable Gram-positive antibacterial activity and potent β-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain β-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3 R, and 3 S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3 R and the 3 S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3 R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, `bioactive' conformer for the classical β-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 α-carboxylate functionality is presented.

On the Kerr-AdS/CFT correspondence

NASA Astrophysics Data System (ADS)

Amado, Julián Barragán; da Cunha, Bruno Carneiro; Pallante, Elisabetta

2017-08-01

We review the relation between four-dimensional global conformal blocks and field propagation in AdS5. Following the standard argument that marginal perturbations should backreact in the geometry, we turn to the study of scalar fields in the generic Kerr-AdS5 geometry. On one hand, the result for scattering coefficients can be obtained exactly using the isomonodromy technique, giving exact expressions in terms of c = 1 chiral conformal blocks. On the other hand, one can use the analogy between the scalar field equations to the Level 2 null field Ward identity in two dimensional Liouville field theory to write approximate expressions for the same coefficients in terms of semi-classical chiral Liouville conformal blocks. Surprisingly, the conformal block thus constructed has a well-behaved interpretation in terms of Liouville vertex operators.

Crystal structure of ethyl (E)-2-cyano-3-(thio-phen-2-yl)acrylate: two conformers forming a discrete disorder.

PubMed

Castro Agudelo, Brian; Cárdenas, Juan C; Macías, Mario A; Ochoa-Puentes, Cristian; Sierra, Cesar A

2017-09-01

In the title compound, C 10 H 9 NO 2 S, all the non-H atoms, except for the ethyl fragment, lie nearly in the same plane. Despite the mol-ecular planarity, the ethyl fragment presents more than one conformation, giving rise to a discrete disorder, which was modelled with two different crystallographic sites for the eth-oxy O and eth-oxy α-C atoms, with occupancy values of 0.5. In the crystal, the three-dimensional array is mainly directed by C-H⋯(O,N) inter-actions, giving rise to inversion dimers with R 2 2 (10) and R 2 2 (14) motifs and infinite chains running along the [100] direction.

Dimensional oscillation. A fast variation of energy embedding gives good results with the AMBER potential energy function.

PubMed

Snow, M E; Crippen, G M

1991-08-01

The structure of the AMBER potential energy surface of the cyclic tetrapeptide cyclotetrasarcosyl is analyzed as a function of the dimensionality of coordinate space. It is found that the number of local energy minima decreases as the dimensionality of the space increases until some limit at which point equipotential subspaces appear. The applicability of energy embedding methods to finding global energy minima in this type of energy-conformation space is explored. Dimensional oscillation, a computationally fast variant of energy embedding is introduced and found to sample conformation space widely and to do a good job of finding global and near-global energy minima.

Dosimetric planning study for the prevention of anal complications after post-operative whole pelvic radiotherapy in cervical cancer patients with hemorrhoids

PubMed Central

Baek, J G; Kim, E C; Kim, S K

2015-01-01

Objective: Radiation-induced anal toxicity can be induced by low radiation doses in patients with haemorrhoids. The object of this study was to determine the dosimetric benefits of different whole pelvic radiotherapy (WPRT) techniques in terms of dose delivered to the anal canal in post-operative patients with cervical cancer. Methods: The planning CT images of 10 patients with cervical cancer undergoing postoperative radiotherapy were used for comparison of three different plans. All patients had been treated using the conventional box technique WPRT (CV-WPRT), and we tried low-margin-modified WPRT (LM-WPRT), three-dimensional conformal techniques WPRT (CF-WPRT) and intensity-modulated WPRT (IM-WPRT) planning for dosimetric comparison of the anal canal, retrospectively. Results: Mean anal canal doses of the IM-WPRT were significantly lower (p < 0.05) than those of CV-WPRT, LM-WPRT and CF-WPRT, and V10, V20, V30 and V40 to the anal canal were also significantly lower for IM-WPRT (p < 0.05). The proportion of planning target volumes (PTVs) that received ≥98% of the prescribed dose for all plans was >99%, and the proportion that received ≥108% of the prescribed dose for IM-WPRT was <2%. Volumes of bladders and rectums that received ≥30 or ≥40 Gy were significantly lower for IM-WPRT than for three of the four-field WPRT plans (p = 0.000). Conclusion: IM-WPRT can significantly reduce radiation dose delivered to the anal canal and does not compromise PTV coverage. In patients with haemorrhoids, IM-WPRT may be of value for the prevention of anal complications. Advances in knowledge: Although tolerance of the anal canal tends to be ignored in patients undergoing post-operative WPRT, patients with haemorrhoids may suffer complications at low radiation doses. The present study shows IM-WPRT can be meaningful in these patients. PMID:26395671

Dosimetric planning study for the prevention of anal complications after post-operative whole pelvic radiotherapy in cervical cancer patients with hemorrhoids.

PubMed

Baek, J G; Kim, E C; Kim, S K; Jang, H

2015-01-01

Radiation-induced anal toxicity can be induced by low radiation doses in patients with haemorrhoids. The object of this study was to determine the dosimetric benefits of different whole pelvic radiotherapy (WPRT) techniques in terms of dose delivered to the anal canal in post-operative patients with cervical cancer. The planning CT images of 10 patients with cervical cancer undergoing postoperative radiotherapy were used for comparison of three different plans. All patients had been treated using the conventional box technique WPRT (CV-WPRT), and we tried low-margin-modified WPRT (LM-WPRT), three-dimensional conformal techniques WPRT (CF-WPRT) and intensity-modulated WPRT (IM-WPRT) planning for dosimetric comparison of the anal canal, retrospectively. Mean anal canal doses of the IM-WPRT were significantly lower (p < 0.05) than those of CV-WPRT, LM-WPRT and CF-WPRT, and V10, V20, V30 and V40 to the anal canal were also significantly lower for IM-WPRT (p < 0.05). The proportion of planning target volumes (PTVs) that received ≥98% of the prescribed dose for all plans was >99%, and the proportion that received ≥108% of the prescribed dose for IM-WPRT was <2%. Volumes of bladders and rectums that received ≥30 or ≥40 Gy were significantly lower for IM-WPRT than for three of the four-field WPRT plans (p = 0.000). IM-WPRT can significantly reduce radiation dose delivered to the anal canal and does not compromise PTV coverage. In patients with haemorrhoids, IM-WPRT may be of value for the prevention of anal complications. Although tolerance of the anal canal tends to be ignored in patients undergoing post-operative WPRT, patients with haemorrhoids may suffer complications at low radiation doses. The present study shows IM-WPRT can be meaningful in these patients.

Performance evaluation of a conformal thermal monitoring sheet (TMS) sensor array for measurement of surface temperature distributions during superficial hyperthermia treatments

PubMed Central

Arunachalam, K.; Maccarini, P.; Juang, T.; Gaeta, C.; Stauffer, P. R.

2009-01-01

Purpose This paper presents a novel conformal thermal monitoring sheet sensor array with differential thermal sensitivity for measuring temperature distributions over large surface areas. Performance of the sensor array is evaluated in terms of thermal accuracy, mechanical stability and conformity to contoured surfaces, probe self heating under irradiation from microwave and ultrasound hyperthermia sources, and electromagnetic field perturbation. Materials and Methods A prototype TMS with 4×4 array of fiberoptic sensors embedded between two flexible and thermally conducting polyimide films was developed as an alternative to the standard 1-2 mm diameter plastic catheter based probes used in clinical hyperthermia. Computed tomography images and bending tests were performed to evaluate the conformability and mechanical stability respectively. Irradiation and thermal barrier tests were conducted and thermal response of the prototype was compared with round cross-sectional clinical probes. Results Bending and conformity tests demonstrated higher flexibility, dimensional stability and close conformity to human torso. Minimal perturbation of microwave fields and low probe self heating was observed when irradiated with 915MHz microwave and 3.4MHz ultrasound sources. The transient and steady state thermal responses of the TMS array were superior compared to the clinical probes. Conclusions A conformal TMS sensor array with improved thermal sensitivity and dimensional stability was investigated for real-time skin temperature monitoring. This fixed-geometry, body-conforming array of thermal sensors allows fast and accurate characterization of two-dimensional temperature distributions over large surface areas. The prototype TMS demonstrates significant advantages over clinical probes for characterizing skin temperature distributions during hyperthermia treatments of superficial tissue disease. PMID:18465416

Four-dimensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal esophageal cancer.

PubMed

Zhang, Xiaodong; Zhao, Kuai-le; Guerrero, Thomas M; McGuire, Sean E; Yaremko, Brian; Komaki, Ritsuko; Cox, James D; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D; Mohan, Radhe; Liao, Zhongxing

2008-09-01

To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.

Application of Optimization Techniques to Design of Unconventional Rocket Nozzle Configurations

NASA Technical Reports Server (NTRS)

Follett, W.; Ketchum, A.; Darian, A.; Hsu, Y.

1996-01-01

Several current rocket engine concepts such as the bell-annular tri-propellant engine, and the linear aerospike being proposed for the X-33 require unconventional three dimensional rocket nozzles which must conform to rectangular or sector shaped envelopes to meet integration constraints. These types of nozzles exist outside the current experience database, therefore, the application of efficient design methods for these propulsion concepts is critical to the success of launch vehicle programs. The objective of this work is to optimize several different nozzle configurations, including two- and three-dimensional geometries. Methodology includes coupling computational fluid dynamic (CFD) analysis to genetic algorithms and Taguchi methods as well as implementation of a streamline tracing technique. Results of applications are shown for several geometeries including: three dimensional thruster nozzles with round or super elliptic throats and rectangualar exits, two- and three-dimensional thrusters installed within a bell nozzle, and three dimensional thrusters with round throats and sector shaped exits. Due to the novel designs considered for this study, there is little experience which can be used to guide the effort and limit the design space. With a nearly infinite parameter space to explore, simple parametric design studies cannot possibly search the entire design space within the time frame required to impact the design cycle. For this reason, robust and efficient optimization methods are required to explore and exploit the design space to achieve high performance engine designs. Five case studies which examine the application of various techniques in the engineering environment are presented in this paper.

The three-dimensional genome organization of Drosophila melanogaster through data integration.

PubMed

Li, Qingjiao; Tjong, Harianto; Li, Xiao; Gong, Ke; Zhou, Xianghong Jasmine; Chiolo, Irene; Alber, Frank

2017-07-31

Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome's organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

Dedicated Stereophotogrammetric X-Ray System For Craniofacial Research And Treatment Planning

NASA Astrophysics Data System (ADS)

Baumrind, Sheldon; Moffitt, Francis; Curry, Sean; Isaacson, Robert J.

1983-07-01

We have constructed and brought into use what we believe to be the first dedicated coplanar craniofacial stereometric x-ray system for clinical use. Paired Machlett Dynamax 50/58 x-ray tubes with 0.3 mm focal spots are employed. Displacement between emitters is 16 inches. The focus film distance for both emitters is 66.5 inches. The mid-sagittal plane to focus distance is 60 inches. One film of each stereo pair conforms with the standards of the Second Roentgenocephalometric Workshop and can be used to make all standard two-dimensional orthodontic and cephalometric measurements. When supplemented by data from the conjugate film, a three-dimensional coordinate map can be generated as a machine operation. Specialized complementary software has been developed to increase the reliability of landmark location both in two and in three dimensions.

Characterizing the Interaction between tartrazine and two serum albumins by a hybrid spectroscopic approach.

PubMed

Pan, Xingren; Qin, Pengfei; Liu, Rutao; Wang, Jing

2011-06-22

Tartrazine is an artificial azo dye commonly used in food products. The present study evaluated the interaction of tartrazine with two serum albumins (SAs), human serum albumin (HSA) and bovine serum albumin (BSA), under physiological conditions by means of fluorescence, three-dimensional fluorescence, UV-vis absorption, and circular dichroism (CD) techniques. The fluorescence data showed that tartrazine could bind to the two SAs to form a complex. The binding process was a spontaneous molecular interaction procedure, in which van der Waals and hydrogen bond interactions played a major role. Additionally, as shown by the UV-vis absorption, three-dimensional fluorescence, and CD results, tartrazine could lead to conformational and some microenvironmental changes of both SAs, which may affect the physiological functions of SAs. The work provides important insight into the mechanism of toxicity of tartrazine in vivo.

Experimental and calculated characteristics of three wings of NACA 64-210 and 65-210 airfoil sections with and without 2 degree washout

NASA Technical Reports Server (NTRS)

Sivells, James C

1947-01-01

Report presents the results of an investigation conducted to determine some of the effects of airfoil section and washout on the experimental and calculated characteristics of 10-percent-thick wings. Three wings of aspect ratio 9 and ratio of root chord to tip chord 2.5 were tested. One wing had NACA 64-210 sections and 2 degree washout, the second had NACA 65-210 sections and 2 degree washout, and the third had NACA 65-210 sections and 0 degree washout. It was found that the experimental characteristics of the wings could be satisfactorily predicted from calculations based upon two-dimensional data when the airfoil contours of the wings conformed to the true airfoil sections with the same high degree of accuracy as the two-dimensional models.

Numerical method for predicting flow characteristics and performance of nonaxisymmetric nozzles. Part 2: Applications

NASA Technical Reports Server (NTRS)

Thomas, P. D.

1980-01-01

A computer implemented numerical method for predicting the flow in and about an isolated three dimensional jet exhaust nozzle is summarized. The approach is based on an implicit numerical method to solve the unsteady Navier-Stokes equations in a boundary conforming curvilinear coordinate system. Recent improvements to the original numerical algorithm are summarized. Equations are given for evaluating nozzle thrust and discharge coefficient in terms of computed flowfield data. The final formulation of models that are used to simulate flow turbulence effect is presented. Results are presented from numerical experiments to explore the effect of various quantities on the rate of convergence to steady state and on the final flowfield solution. Detailed flowfield predictions for several two and three dimensional nozzle configurations are presented and compared with wind tunnel experimental data.

Diagnosing Chaos Using Four-Point Functions in Two-Dimensional Conformal Field Theory.

PubMed

Roberts, Daniel A; Stanford, Douglas

2015-09-25

We study chaotic dynamics in two-dimensional conformal field theory through out-of-time-order thermal correlators of the form ⟨W(t)VW(t)V⟩. We reproduce holographic calculations similar to those of Shenker and Stanford, by studying the large c Virasoro identity conformal block. The contribution of this block to the above correlation function begins to decrease exponentially after a delay of ~t_{*}-(β/2π)logβ^{2}E_{w}E_{v}, where t_{*} is the fast scrambling time (β/2π)logc and E_{w},E_{v} are the energy scales of the W,V operators.

GPU surface extraction using the closest point embedding

NASA Astrophysics Data System (ADS)

Kim, Mark; Hansen, Charles

2015-01-01

Isosurface extraction is a fundamental technique used for both surface reconstruction and mesh generation. One method to extract well-formed isosurfaces is a particle system; unfortunately, particle systems can be slow. In this paper, we introduce an enhanced parallel particle system that uses the closest point embedding as the surface representation to speedup the particle system for isosurface extraction. The closest point embedding is used in the Closest Point Method (CPM), a technique that uses a standard three dimensional numerical PDE solver on two dimensional embedded surfaces. To fully take advantage of the closest point embedding, it is coupled with a Barnes-Hut tree code on the GPU. This new technique produces well-formed, conformal unstructured triangular and tetrahedral meshes from labeled multi-material volume datasets. Further, this new parallel implementation of the particle system is faster than any known methods for conformal multi-material mesh extraction. The resulting speed-ups gained in this implementation can reduce the time from labeled data to mesh from hours to minutes and benefits users, such as bioengineers, who employ triangular and tetrahedral meshes

GCD TechPort Data Sheets Thermal Protection System Materials (TPSM) Project

NASA Technical Reports Server (NTRS)

Chinnapongse, Ronald L.

2014-01-01

The Thermal Protection System Materials (TPSM) Project consists of three distinct project elements: the 3-Dimensional Multifunctional Ablative Thermal Protection System (3D MAT) project element; the Conformal Ablative Thermal Protection System (CA-TPS) project element; and the Heatshield for Extreme Entry Environment Technology (HEEET) project element. 3D MAT seeks to design, develop and deliver a game changing material solution based on 3-dimensional weaving and resin infusion approach for manufacturing a material that can function as a robust structure as well as a thermal protection system. CA-TPS seeks to develop and deliver a conformal ablative material designed to be efficient and capable of withstanding peak heat flux up to 500 W/ sq cm, peak pressure up to 0.4 atm, and shear up to 500 Pa. HEEET is developing a new ablative TPS that takes advantage of state-of-the-art 3D weaving technologies and traditional manufacturing processes to infuse woven preforms with a resin, machine them to shape, and assemble them as a tiled solution on the entry vehicle substructure or heatshield.

NMR structure and conformational dynamics of AtPDFL2.1, a defensin-like peptide from Arabidopsis thaliana.

PubMed

Omidvar, Reza; Xia, Youlin; Porcelli, Fernando; Bohlmann, Holger; Veglia, Gianluigi

2016-12-01

Plant defensins constitute the innate immune response against pathogens such as fungi and bacteria. Typical plant defensins are small, basic peptides that possess a characteristic three-dimensional fold stabilized by three or four disulfide bridges. In addition to known defensin genes, the Arabidopsis genome comprises >300 defensin-like genes coding for small cysteine-rich peptides. One of such genes encodes for AtPDFL2.1, a putative antifungal peptide of 55 amino acids, with six cysteine residues in its primary sequence. To understand the functional role of AtPDFL2.1, we carried out antifungal activity assays and determined its high-resolution three-dimensional structure using multidimensional solution NMR spectroscopy. We found that AtPDFL2.1 displays a strong inhibitory effect against Fusarium graminearum (IC 50 ≈4μM). This peptide folds in the canonical cysteine-stabilized αβ (CSαβ) motif, consisting of one α-helix and one triple-stranded antiparallel β-sheet stabilized by three disulfide bridges and a hydrophobic cluster of residues within its core where the α-helix packs tightly against the β-sheets. Nuclear spin relaxation measurements show that the structure of AtPDFL2.1 is essentially rigid, with the L3 loop located between β-strands 2 and 3 being more flexible and displaying conformational exchange. Interestingly, the dynamic features of loop L3 are conserved among defensins and are probably correlated to the antifungal and receptor binding activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Supergravitational conformal Galileons

DOE PAGES

Deen, Rehan; Ovrut, Burt

2017-08-04

The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and “bouncing” cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory,more » but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios« less

Supergravitational conformal Galileons

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

Deen, Rehan; Ovrut, Burt

The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and “bouncing” cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory,more » but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios« less

Analysis of Transient Electromagnetic Scattering from Three Dimensional Cavities

DTIC Science & Technology

2014-01-01

New York, 2002. [24] J. Jin and J. L. Volakis, A hybrid finite element method for scattering and radiation by micro strip patch antennas and arrays...applications such as the design of cavity-backed conformal antennas and the deliberate control in the form of enhancement or reduction of radar cross...electromagnetic scattering analysis, IEEE Trans. Antennas Propagat., 50 (2002), pp. 1192–1202. [22] J. Jin, Electromagnetic scattering from large, deep, and

The concept and evolution of involved site radiation therapy for lymphoma.

PubMed

Specht, Lena; Yahalom, Joachim

2015-10-01

We describe the development of radiation therapy for lymphoma from extended field radiotherapy of the past to modern conformal treatment with involved site radiation therapy based on advanced imaging, three-dimensional treatment planning and advanced treatment delivery techniques. Today, radiation therapy is part of the multimodality treatment of lymphoma, and the irradiated tissue volume is much smaller than before, leading to highly significant reductions in the risks of long-term complications.

4-Benzyl-4-ethyl­morpholin-1-ium hexa­fluoro­phosphate

PubMed Central

Yang, Fang; Zang, Hongjun; Cheng, Bowen; Xu, Xianlin; Ren, Yuanlin

2012-01-01

The asymmetric unit of the title compound, C13H20NO+·PF6 −, contains two cations, one complete anion and two half hexa­fluoro­phosphate anions having crystallographically imposed twofold rotation symmetry. In the cations, the morpholine rings are in a chair conformation. In the crystal, ions are linked by weak C—H⋯F hydrogen bonds into a three-dimensional network. PMID:22412701

Impact of computed tomography and {sup 18}F-deoxyglucose coincidence detection emission tomography image fusion for optimization of conformal radiotherapy in non-small-cell lung cancer

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

Deniaud-Alexandre, Elisabeth; Touboul, Emmanuel; Lerouge, Delphine

2005-12-01

Purpose: To report a retrospective study concerning the impact of fused {sup 18}F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and CT images on three-dimensional conformal radiotherapy planning for patients with non-small-cell lung cancer. Methods and Materials: A total of 101 patients consecutively treated for Stage I-III non-small-cell lung cancer were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images, and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define themore » target volume. Results: {sup 18}F-fluoro-deoxy-D-glucose-PET identified previously undetected distant metastatic disease in 8 patients, making them ineligible for curative conformal radiotherapy (1 patient presented with some positive uptake corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because the fused PET-CT images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT-PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was {>=}25% in 7 patients because CT-PET image fusion reduced the pulmonary GTV in 6 patients (3 patients with atelectasis) and the mediastinal nodal GTV in 1 patient. The GTV increase was {>=}25% in 14 patients owing to an increase in the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Of 81 patients receiving a total dose of {>=}60 Gy at the International Commission on Radiation Units and Measurements point, after CT-PET image fusion, the percentage of total lung volume receiving >20 Gy increased in 15 cases and decreased in 22. The percentage of total heart volume receiving >36 Gy increased in 8 patients and decreased in 14. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. Multivariate analysis showed that tumor with atelectasis was the single independent factor that resulted in a significant effect on the modification of the size of the GTV by FDG-PET: tumor with atelectasis (with vs. without atelectasis, p = 0.0001). Conclusion: The results of our study have confirmed that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of non-small-cell lung cancer. However, FDG images using dedicated PET scanners and respiration-gated acquisition protocols could improve the PET-CT image coregistration. Furthermore, the impact on treatment outcome remains to be demonstrated.« less

Compactification on phase space

NASA Astrophysics Data System (ADS)

Lovelady, Benjamin; Wheeler, James

2016-03-01

A major challenge for string theory is to understand the dimensional reduction required for comparison with the standard model. We propose reducing the dimension of the compactification by interpreting some of the extra dimensions as the energy-momentum portion of a phase-space. Such models naturally arise as generalized quotients of the conformal group called biconformal spaces. By combining the standard Kaluza-Klein approach with such a conformal gauge theory, we may start from the conformal group of an n-dimensional Euclidean space to form a 2n-dimensional quotient manifold with symplectic structure. A pair of involutions leads naturally to two n-dimensional Lorentzian manifolds. For n = 5, this leaves only two extra dimensions, with a countable family of possible compactifications and an SO(5) Yang-Mills field on the fibers. Starting with n=6 leads to 4-dimensional compactification of the phase space. In the latter case, if the two dimensions each from spacetime and momentum space are compactified onto spheres, then there is an SU(2)xSU(2) (left-right symmetric electroweak) field between phase and configuration space and an SO(6) field on the fibers. Such a theory, with minor additional symmetry breaking, could contain all parts of the standard model.

Two-dimensional vibrational spectroscopy of the amide I band of crystalline acetanilide: Fermi resonance, conformational substates, or vibrational self-trapping?

NASA Astrophysics Data System (ADS)

Edler, J.; Hamm, P.

2003-08-01

Two-dimensional infrared (2D-IR) spectroscopy is applied to investigate acetanilide, a molecular crystal consisting of quasi-one-dimensional hydrogen bonded peptide units. The amide-I band exhibits a double peak structure, which has been attributed to different mechanisms including vibrational self-trapping, a Fermi resonance, or the existence of two conformational substates. The 2D-IR spectrum of crystalline acetanilide is compared with that of two different molecular systems: (i) benzoylchloride, which exhibits a strong symmetric Fermi resonance and (ii) N-methylacetamide dissolved in methanol which occurs in two spectroscopically distinguishable conformations. Both 2D-IR spectra differ significantly from that of crystalline acetanilide, proving that these two alternative mechanisms cannot account for the anomalous spectroscopy of crystalline acetanilide. On the other hand, vibrational self-trapping of the amide-I band can naturally explain the 2D-IR response.

Measurement of radiation dose with BeO dosimeters using optically stimulated luminescence technique in radiotherapy applications.

PubMed

Şahin, Serdar; Güneş Tanır, A; Meriç, Niyazi; Aydınkarahaliloğlu, Ercan

2015-09-01

The radiation dose delivered to the target by using different radiotherapy applications has been measured with the help of beryllium oxide (BeO) dosimeters to be placed inside the rando phantom. Three-Dimensional Conformal Radiotherapy (3DCRT), Intensity-Modulated Radiotherapy (IMRT) and Intensity-Modulated Arc Therapy (IMAT) have been used as radiotherapy application. Individual treatment plans have been made for the three radiotherapy applications of rando phantom. The section 4 on the phantom was selected as target and 200 cGy doses were delivered. After the dosimeters placed on section 4 (target) and the sections 2 and 6 (non-target) were irradiated, the result was read through the OSL technique on the Risø TL/OSL system. This procedure was repeated three times for each radiotherapy application. The doses delivered to the target and the non-target sections as a result of the 3DCRT, IMRT and IMAT plans were analyzed. The doses received by the target were measured as 204.71 cGy, 204.76 cGy and 205.65 cGy, respectively. The dose values obtained from treatment planning system (TPS) were compared to the dose values obtained using the OSL technique. It has been concluded that, the radiation dose can be measured with the OSL technique by using BeO dosimeters in medical practices. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling

NASA Astrophysics Data System (ADS)

Laimou, Despina; Lazoura, Eliada; Troganis, Anastassios N.; Matsoukas, Minos-Timotheos; Deraos, Spyros N.; Katsara, Maria; Matsoukas, John; Apostolopoulos, Vasso; Tselios, Theodore V.

2011-11-01

Τwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP1-11) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP1-11[4A]) or a tyrosine residue (Ac-MBP1-11[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-Au was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln3 residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-Au complex, has a different orientation in the mutated analogues especially in the Ac-MBP1-11[4A] peptide. In particular the side chain of Gln3 is not solvent exposed as for the native Ac-MBP1-11 and it is not available for interaction with the TCR.

The conformal characters

NASA Astrophysics Data System (ADS)

Bourget, Antoine; Troost, Jan

2018-04-01

We revisit the study of the multiplets of the conformal algebra in any dimension. The theory of highest weight representations is reviewed in the context of the Bernstein-Gelfand-Gelfand category of modules. The Kazhdan-Lusztig polynomials code the relation between the Verma modules and the irreducible modules in the category and are the key to the characters of the conformal multiplets (whether finite dimensional, infinite dimensional, unitary or non-unitary). We discuss the representation theory and review in full generality which representations are unitarizable. The mathematical theory that allows for both the general treatment of characters and the full analysis of unitarity is made accessible. A good understanding of the mathematics of conformal multiplets renders the treatment of all highest weight representations in any dimension uniform, and provides an overarching comprehension of case-by-case results. Unitary highest weight representations and their characters are classified and computed in terms of data associated to cosets of the Weyl group of the conformal algebra. An executive summary is provided, as well as look-up tables up to and including rank four.

Prediction of vortex shedding from circular and noncircular bodies in subsonic flow

NASA Technical Reports Server (NTRS)

Mendenhall, Michael R.; Lesieutre, Daniel J.

1987-01-01

An engineering prediction method and associated computer code VTXCLD are presented which predict nose vortex shedding from circular and noncircular bodies in subsonic flow at angles of attack and roll. The axisymmetric body is represented by point sources and doublets, and noncircular cross sections are transformed to a circle by either analytical or numerical conformal transformations. The leeward vortices are modeled by discrete vortices in crossflow planes along the body; thus, the three-dimensional steady flow problem is reduced to a two-dimensional, unsteady, separated flow problem for solution. Comparison of measured and predicted surface pressure distributions, flowfield surveys, and aerodynamic characteristics are presented for bodies with circular and noncircular cross sectional shapes.

Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers

PubMed Central

Bhide, S A; Newbold, K L; Harrington, K J; Nutting, C M

2012-01-01

Radiotherapy and surgery are the principal curative modalities in treatment of head and neck cancer. Conventional two-dimensional and three-dimensional conformal radiotherapy result in significant side effects and altered quality of life. Intensity-modulated radiotherapy (IMRT) can spare the normal tissues, while delivering a curative dose to the tumour-bearing tissues. This article reviews the current role of IMRT in head and neck cancer from the point of view of normal tissue sparing, and also reviews the current published literature by individual head and neck cancer subsites. In addition, we briefly discuss the role of image guidance in head and neck IMRT, and future directions in this area. PMID:22556403

Modeling and docking antibody structures with Rosetta

PubMed Central

Weitzner, Brian D.; Jeliazkov, Jeliazko R.; Lyskov, Sergey; Marze, Nicholas; Kuroda, Daisuke; Frick, Rahel; Adolf-Bryfogle, Jared; Biswas, Naireeta; Dunbrack, Roland L.; Gray, Jeffrey J.

2017-01-01

We describe Rosetta-based computational protocols for predicting the three-dimensional structure of an antibody from sequence (RosettaAntibody) and then docking the antibody to protein antigens (SnugDock). Antibody modeling leverages canonical loop conformations to graft large segments from experimentally-determined structures as well as (1) energetic calculations to minimize loops, (2) docking methodology to refine the VL–VH relative orientation, and (3) de novo prediction of the elusive complementarity determining region (CDR) H3 loop. To alleviate model uncertainty, antibody–antigen docking resamples CDR loop conformations and can use multiple models to represent an ensemble of conformations for the antibody, the antigen or both. These protocols can be run fully-automated via the ROSIE web server (http://rosie.rosettacommons.org/) or manually on a computer with user control of individual steps. For best results, the protocol requires roughly 1,000 CPU-hours for antibody modeling and 250 CPU-hours for antibody–antigen docking. Tasks can be completed in under a day by using public supercomputers. PMID:28125104

Modeling of Oligosaccharides within Glycoproteins from Free-Energy Landscapes

PubMed Central

2017-01-01

In spite of the abundance of glycoproteins in biological processes, relatively little three-dimensional structural data is available for glycan structures. Here, we study the structure and flexibility of the vast majority of mammalian oligosaccharides appearing in N- and O-glycosylated proteins using a bottom up approach. We report the conformational free-energy landscapes of all relevant glycosidic linkages as obtained from local elevation simulations and subsequent umbrella sampling. To the best of our knowledge, this represents the first complete conformational library for the construction of N- and O-glycan structures. Next, we systematically study the effect of neighboring residues, by extensively simulating all relevant trisaccharides and one tetrasaccharide. This allows for an unprecedented comparison of disaccharide linkages in large oligosaccharides. With a small number of exceptions, the conformational preferences in the larger structures are very similar as in the disaccharides. This, finally, allows us to suggest several efficient approaches to construct complete N- and O-glycans on glycoproteins, as exemplified on two relevant examples. PMID:28816453

Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy.

PubMed

Fischer, Niels; Konevega, Andrey L; Wintermeyer, Wolfgang; Rodnina, Marina V; Stark, Holger

2010-07-15

The translocation step of protein synthesis entails large-scale rearrangements of the ribosome-transfer RNA (tRNA) complex. Here we have followed tRNA movement through the ribosome during translocation by time-resolved single-particle electron cryomicroscopy (cryo-EM). Unbiased computational sorting of cryo-EM images yielded 50 distinct three-dimensional reconstructions, showing the tRNAs in classical, hybrid and various novel intermediate states that provide trajectories and kinetic information about tRNA movement through the ribosome. The structures indicate how tRNA movement is coupled with global and local conformational changes of the ribosome, in particular of the head and body of the small ribosomal subunit, and show that dynamic interactions between tRNAs and ribosomal residues confine the path of the tRNAs through the ribosome. The temperature dependence of ribosome dynamics reveals a surprisingly flat energy landscape of conformational variations at physiological temperature. The ribosome functions as a Brownian machine that couples spontaneous conformational changes driven by thermal energy to directed movement.

2010 Award for Outstanding Doctoral Thesis Research in Biological Physics Talk: How the Genome Folds

NASA Astrophysics Data System (ADS)

Lieberman-Aiden, Erez

2011-03-01

I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

On low-energy effective action in three-dimensional = 2 and = 4 supersymmetric electrodynamics

NASA Astrophysics Data System (ADS)

Buchbinder, I. L.; Merzlikin, B. S.; Samsonov, I. B.

2013-11-01

We discuss general structure of low-energy effective actions in = 2 and = 4 three-dimensional supersymmetric electrodynamics (SQED) in gauge superfield sector. There are specific terms in the effective action having no four-dimensional analogs. Some of these terms are responsible for the moduli space metric in the Coulomb branch of the theory. We find two-loop quantum corrections to the moduli space metric in the = 2 SQED and show that in the = 4 SQED the moduli space does not receive two-loop quantum corrections.

Reproducibility of patient positioning for fractionated extracranial stereotactic radiotherapy using a double-vacuum technique.

PubMed

Nevinny-Stickel, Meinhard; Sweeney, Reinhart A; Bale, Reto J; Posch, Andrea; Auberger, Thomas; Lukas, Peter

2004-02-01

Precise reproducible patient positioning is a prerequisite for conformal fractionated radiotherapy. A fixation system based on double-vacuum technology is presented which can be used for conventional as well as hypofractionated stereotactic extracranial radiotherapy. To form the actual vacuum mattress, the patient is pressed into the mattress with a vacuum foil which can also be used for daily repositioning and fixation. A stereotactic frame can be positioned over the region of interest on an indexed base plate. Repositioning accuracy was determined by comparing daily, pretreatment, orthogonal portal images to the respective digitally reconstructed radiographs (DRRs) in ten patients with abdominal and pelvic lesions receiving extracranial fractionated (stereotactic) radiotherapy. The three-dimensional (3-D) vectors and 95% confidence intervals (CI) were calculated from the respective deviations in the three axes. Time required for initial mold production and daily repositioning was also determined. The mean 3-D repositioning error (187 fractions) was 2.5 +/- 1.1 mm. The largest single deviation (10 mm) was observed in a patient treated in prone position. Mold production took an average of 15 min (10-30 min). Repositioning times are not necessarily longer than using no positioning aid at all. The presented fixation system allows reliable, flexible and efficient patient positioning for extracranial stereotactic radiotherapy.

Multiple-step relayed correlation spectroscopy: sequential resonance assignments in oligosaccharides.

PubMed Central

Homans, S W; Dwek, R A; Fernandes, D L; Rademacher, T W

1984-01-01

A general property of the high-resolution proton NMR spectra of oligosaccharides is the appearance of low-field well-resolved resonances corresponding to the anomeric (H1) and H2 protons. The remaining skeletal protons resonate in the region 3-4 ppm, giving rise to an envelope of poorly resolved resonances. Assignments can be made from the H1 and H2 protons to their J-coupled neighbors (H2 and H3) within this main envelope by using 1H-1H correlated spectroscopy. However, the tight coupling (J congruent to delta) between further protons results in poor spectral dispersion with consequent assignment ambiguities. We describe here three-step two-dimensional relayed correlation spectroscopy and show how it can be used to correlate the resolved anomeric (H1) and H2 protons with remote (H4, H5) protons directly through a linear network of couplings using sequential magnetization transfer around the oligosaccharide rings. Resonance assignments are then obtained by inspection of cross-peaks that appear in well-resolved regions of the two-dimensional spectrum. This offers a general solution to the assignment problem in oligosaccharides and, importantly, these assignments will subsequently allow for the three-dimensional solution conformation to be determined by using one-dimensional and two-dimensional nuclear Overhauser experiments. PMID:6593701

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

PubMed Central

Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R.

2015-01-01

Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called “repeat-swap modeling” to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also occurs via an elevator-like mechanism. PMID:26388773

Scaling relations for a functionally two-dimensional plant: Chamaesyce setiloba (Euphorbiaceae).

PubMed

Koontz, Terri L; Petroff, Alexander; West, Geoffrey B; Brown, James H

2009-05-01

Many characteristics of plants and animals scale with body size as described by allometric equations of the form Y = βM(α), where Y is an attribute of the organism, β is a coefficient that varies with attribute, M is a measure of organism size, and α is another constant, the scaling exponent. In current models, the frequently observed quarter-power scaling exponents are hypothesized to be due to fractal-like structures. However, not all plants or animals conform to the assumptions of these models. Therefore, they might be expected to have different scaling relations. We studied one such plant, Chamaesyce setiloba, a prostrate annual herb that grows to functionally fill a two-dimensional space. Number of leaves scaled slightly less than isometrically with total aboveground plant mass (α ≈ 0.9) and substantially less than isometrically with dry total stem mass (α = 0.82), showing reduced allocation to leaf as opposed to stem tissue with increasing plant size. Additionally, scalings of the lengths and radii of parent and daughter branches differed from those predicted for three-dimensional trees and shrubs. Unlike plants with typical three-dimensional architectures, C. setiloba has distinctive scaling relations associated with its particular prostrate herbaceous growth form.

An algebraic homotopy method for generating quasi-three-dimensional grids for high-speed configurations

NASA Technical Reports Server (NTRS)

Moitra, Anutosh

1989-01-01

A fast and versatile procedure for algebraically generating boundary conforming computational grids for use with finite-volume Euler flow solvers is presented. A semi-analytic homotopic procedure is used to generate the grids. Grids generated in two-dimensional planes are stacked to produce quasi-three-dimensional grid systems. The body surface and outer boundary are described in terms of surface parameters. An interpolation scheme is used to blend between the body surface and the outer boundary in order to determine the field points. The method, albeit developed for analytically generated body geometries is equally applicable to other classes of geometries. The method can be used for both internal and external flow configurations, the only constraint being that the body geometries be specified in two-dimensional cross-sections stationed along the longitudinal axis of the configuration. Techniques for controlling various grid parameters, e.g., clustering and orthogonality are described. Techniques for treating problems arising in algebraic grid generation for geometries with sharp corners are addressed. A set of representative grid systems generated by this method is included. Results of flow computations using these grids are presented for validation of the effectiveness of the method.

Comparative outcomes for three-dimensional conformal versus intensity-modulated radiation therapy for esophageal cancer.

PubMed

Freilich, J; Hoffe, S E; Almhanna, K; Dinwoodie, W; Yue, B; Fulp, W; Meredith, K L; Shridhar, R

2015-01-01

Emerging data suggests a benefit for using intensity modulated radiation therapy (IMRT) for the management of esophageal cancer. We retrospectively reviewed patients treated at our institution who received definitive or preoperative chemoradiation with either IMRT or 3D conformal radiation therapy (3DCRT) between October 2000 and January 2012. Kaplan Meier analysis and the Cox proportional hazard model were used to evaluate survival outcomes. We evaluated a total of 232 patients (138 IMRT, 94 3DCRT) who received a median dose of 50.4 Gy (range, 44-64.8) to gross disease. Median follow up for all patients, IMRT patients alone, and 3DCRT patients alone was 18.5 (range, 2.5-124.2), 16.5 (range, 3-59), and 25.9 months (range, 2.5-124.2), respectively. We observed no significant difference based on radiation technique (3DCRT vs. IMRT) with respect to median overall survival (OS) (median 29 vs. 32 months; P = 0.74) or median relapse free survival (median 20 vs. 25 months; P = 0.66). On multivariable analysis (MVA), surgical resection resulted in improved OS (HR 0.444; P < 0.0001). Superior OS was also associated on MVA with stage I/II disease (HR 0.523; P = 0.010) and tumor length ≤5 cm (HR 0.567; P = 0.006). IMRT was also associated on univariate analysis with a significant decrease in acute weight loss (mean 6% + 4.3% vs 9% + 7.4%, P = 0.012) and on MVA with a decrease in objective grade ≥3 toxicity, defined as any hospitalization, feeding tube, or >20% weight loss (OR 0.51; P = 0.050). Our data suggest that while IMRT-based chemoradiation for esophageal cancer does not impact survival there was significantly less toxicity. In the IMRT group there was significant decrease in weight loss and grade ≥3 toxicity compared to 3DCRT. © 2014 International Society for Diseases of the Esophagus.

The effect on esophagus after different radiotherapy techniques for early stage Hodgkin's lymphoma.

PubMed

Jørgensen, Anni Y S; Maraldo, Maja V; Brodin, Nils Patrik; Aznar, Marianne C; Vogelius, Ivan R; Rosenschöld, Per Munck Af; Petersen, Peter M; Specht, Lena

2013-10-01

The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments. We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections. Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001). The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future.

Tris[(6S)-6-hy-droxy-4-epi-shikimic acid] monohydrate: an enanti-omerically pure hy-droxy-lated shikimic acid derived from methyl shikimate.

PubMed

Griesbeck, Axel G; Miara, Claus; Neudörfl, Jörg-M

2012-11-01

The title compound, 3C(7)H(10)O(6)·H(2)O, is the enanti-omerically pure product of a multi-step synthesis from the enanti-omerically pure natural shikimic acid. The asymmetric unit contains three mol-ecules of the acid and one mol-ecule of water. The cyclo-hexene rings of the acids have half-chair conformations. The carboxyl-ate, the four hydroxide groups and the additional water mol-ecule form a complex three-dimensional hydrogen-bonding network.

Intensity-modulated radiation therapy: a review with a physics perspective.

PubMed

Cho, Byungchul

2018-03-01

Intensity-modulated radiation therapy (IMRT) has been considered the most successful development in radiation oncology since the introduction of computed tomography into treatment planning that enabled three-dimensional conformal radiotherapy in 1980s. More than three decades have passed since the concept of inverse planning was first introduced in 1982, and IMRT has become the most important and common modality in radiation therapy. This review will present developments in inverse IMRT treatment planning and IMRT delivery using multileaf collimators, along with the associated key concepts. Other relevant issues and future perspectives are also presented.

Comparison of 3DCRT,VMAT and IMRT techniques in metastatic vertebra radiotherapy: A phantom Study

NASA Astrophysics Data System (ADS)

Gedik, Sonay; Tunc, Sema; Kahraman, Arda; Kahraman Cetintas, Sibel; Kurt, Meral

2017-09-01

Vertebra metastases can be seen during the prognosis of cancer patients. Treatment ways of the metastasis are radiotherapy, chemotherapy and surgery. Three-dimensional conformal therapy (3D-CRT) is widely used in the treatment of vertebra metastases. Also, Intensity Modulated Radiotherapy (IMRT) and Volumetric Arc Therapy (VMAT) are used too. The aim of this study is to examine the advantages and disadvantages of the different radiotherapy techniques. In the aspect of this goal, it is studied with a randophantom in Uludag University Medicine Faculty, Radiation Oncology Department. By using a computerized tomography image of the phantom, one 3DCRT plan, two VMAT and three IMRT plans for servical vertebra and three different 3DCRT plans, two VMAT and two IMRT plans for lomber vertebra are calculated. To calculate 3DCRT plans, CMS XiO Treatment System is used and to calculate VMAT and IMRT plans Monaco Treatment Planning System is used in the department. The study concludes with the dosimetric comparison of the treatment plans in the spect of critical organ doses, homogeneity and conformity index. As a result of this study, all critical organ doses are suitable for QUANTEC Dose Limit Report and critical organ doses depend on the techniques which used in radiotherapy. According to homogeneity and conformity indices, VMAT and IMRT plans are better than one in 3DCRT plans in servical and lomber vertebra radiotherapy plans.

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

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

Nichols, Elizabeth, E-mail: Enichols1@umm.edu; Kesmodel, Susan B.; Bellavance, Emily

Purpose: To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy. Patients and Methods: This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (<3 cm), N0 tumors. Patients received 38.5 Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed >21 days after radiation therapy. Adjuvant therapy was given as per standard of care. Results: Twenty-seven patients completed treatment. With a median follow-up of 3.6 years (range, 0.5-5 years), there have been no local or regional failures.more » A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment. Conclusions: Preoperative 3-dimensional conformal radiation therapy−APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.« less

A new three-dimensional conformal radiotherapy (3DCRT) technique for large breast and/or high body mass index patients: evaluation of a novel fields assessment aimed to reduce extra-target-tissue irradiation.

PubMed

Gerardina, Stimato; Edy, Ippolito; Sonia, Silipigni; Cristina, Di Venanzio; Carla Germana, Rinaldi; Diego, Gaudino; Michele, Fiore; Lucio, Trodella; Maria, D'Angelillo Rolando; Sara, Ramella

2016-09-01

To develop an alternative three-dimensional treatment plan with standardized fields class solution for whole-breast radiotherapy in patients with large/pendulous breast and/or high body mass index (BMI). Two treatment plans [tangential fields and standardized five-fields technique (S5F)] for a total dose of 50 Gy/25 fractions were generated for patients with large breasts [planning target volume (PTV) >1000 cm(3) and/or BMI >25 kg m(-2)], supine positioned. S5F plans consist of two wedged tangential beams, anteroposterior: 20° for the right breast and 340° for the left breast, and posteroanterior: 181° for the right breast and 179° for the left breast. A field in field in medial-lateral beam and additional fields were added to reduce hot spot areas and extra-target-tissue irradiation and to improve dose distribution. The percentage of PTV receiving 95% of the prescribed dose (PTV V95%), percentage of PTV receiving 105% of the prescribed dose (PTV V105%), maximal dose to PTV (PTV Dmax), homogeneity index (HI) and conformity index were recorded. V10%, V20%, V105% and V107% of a "proper" normal tissue structure (body-PTV healthy tissue) were recorded. Statistical analyses were performed using SYSTAT v.12.0 (SPSS, Chicago, IL). In 38 patients included, S5F improved HI (8.4 vs 10.1; p ≤ 0.001) and significantly reduced PTV Dmax and PTV V105%. The extra-target-tissue irradiation was significantly reduced using S5F for V105% (cm(3)) and V107% (cm(3)) with a very high difference in tissue irradiation (46.6 vs 3.0 cm(3), p ≤ 0.001 for V105% and 12.2 vs 0.0 cm(3), p ≤ 0.001 for V107% for tangential field and S5F plans, respectively). Only a slight increase in low-dose extra-target-tissue irradiation (V10%) was observed (2.2719 vs 1.8261 cm(3), p = 0.002). The S5F technique in patients with large breast or high BMI increases HI and decreases hot spots in extra-target-tissues and can therefore be easily implemented in breast cancer radiotherapy. The treatment planning strategy proposed in this study has several advantages: (a) it is extremely reliable as the standard supine positioning is used; (b) the standardized class solution allows for widespread use; (c) time and cost of treatment are not increased; and (d) it can be used for both large breasted and obese patients not compliant to different treatment positioning.

Conformal mapping and bound states in bent waveguides

NASA Astrophysics Data System (ADS)

Sadurní, E.; Schleich, W. P.

2010-12-01

Is it possible to trap a quantum particle in an open geometry? In this work we deal with the boundary value problem of the stationary Schroedinger (or Helmholtz) equation within a waveguide with straight segments and a rectangular bending. The problem can be reduced to a one-dimensional matrix Schroedinger equation using two descriptions: oblique modes and conformal coordinates. We use a corner-corrected WKB formalism to find the energies of the one-dimensional problem. It is shown that the presence of bound states is an effect due to the boundary alone, with no classical counterpart for this geometry. The conformal description proves to be simpler, as the coupling of transversal modes is not essential in this case.

Classification of Kantowski-Sachs metric via conformal Ricci collineations

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Khan, Fawad; Bokhari, Ashfaque H.; Akhtar, Sumaira Saleem

In this paper, we present a classification of the Kantowski-Sachs spacetime metric according to its conformal Ricci collineations (CRCs). Solving the CRC equations, it is shown that the Kantowski-Sachs metric admits 15-dimensional Lie algebra of CRCs when its Ricci tensor is non-degenerate and an infinite dimensional group of CRCs when the Ricci tensor is degenerate. Some examples of Kantowski-Sachs metric admitting nontrivial CRCs are presented and their physical interpretation is provided.

Velocity distributions on two-dimensional wing-duct inlets by conformal mapping

NASA Technical Reports Server (NTRS)

Perl, W; Moses, H E

1948-01-01

The conformal-mapping method of the Cartesian mapping function is applied to the determination of the velocity distribution on arbitrary two-dimensional duct-inlet shapes such as are used in wing installations. An idealized form of the actual wing-duct inlet is analyzed. The effects of leading edge stagger, inlet-velocity ratio, and section lift coefficients on the velocity distribution are included in the analysis. Numerical examples are given and, in part, compared with experimental data.

A Three-Dimensional Model of the Yeast Genome

NASA Astrophysics Data System (ADS)

Noble, William; Duan, Zhi-Jun; Andronescu, Mirela; Schutz, Kevin; McIlwain, Sean; Kim, Yoo Jung; Lee, Choli; Shendure, Jay; Fields, Stanley; Blau, C. Anthony

Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or factories for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.

Structure and Uncoating of Immature Adenovirus

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

Perez-Berna, A.J.; Mangel, W.; Marabini, R.

2009-09-18

Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particlesmore » as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.« less

Sexual Function After Three-Dimensional Conformal Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

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

Wielen, Gerard J. van der; Putten, Wim van; Incrocci, Luca

Purpose: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF. Methods and Materials: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF. Results: At baseline 28% of patients had erectile dysfunction (ED). After 1 year, 27% of the pretreatment potent patients had developed ED. After 2 years this percentage had increased to 36%.more » After 3 years it almost stabilized at 38%. Satisfaction with sexual life was significantly correlated with ED. After 2 years one third of the pre-treatment potent patients still had considerable to very much sexual desire and found sex (very) important. No significant differences were found between the two dose-arms. Potency aids were used on a regular base by 14% of the patients. Conclusion: By taking adjuvant hormonal therapy (HT), HT during follow-up and potency aids into account, we found a lower percentage of ED after 3D-CRT than reported in previous prospective studies. A large group of patients still had sexual desire, considered sex important and 14% used potency aids after 3D-CRT.« less

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

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations inmore » 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.« less

Single photon imaging and timing array sensor apparatus and method

DOEpatents

Smith, R. Clayton

2003-06-24

An apparatus and method are disclosed for generating a three-dimension image of an object or target. The apparatus is comprised of a photon source for emitting a photon at a target. The emitted photons are received by a photon receiver for receiving the photon when reflected from the target. The photon receiver determines a reflection time of the photon and further determines an arrival position of the photon on the photon receiver. An analyzer is communicatively coupled to the photon receiver, wherein the analyzer generates a three-dimensional image of the object based upon the reflection time and the arrival position.

Correlation Functions in Two-Dimensional Critical Systems with Conformal Symmetry

NASA Astrophysics Data System (ADS)

Flores, Steven Miguel

This thesis presents a study of certain conformal field theory (CFT) correlation functions that describe physical observables in conform ally invariant two-dimensional critical systems. These are typically continuum limits of critical lattice models in a domain within the complex plane and with a boundary. Certain clusters, called boundary clusters, anchor to the boundary of the domain, and many of their features are governed by a conformally invariant probability measure. For example, percolaion is an example of a critical lattice model, and when it is confined to a domain with a boundary, connected clusters of activated bonds that touch that boundary are the boundary clusters. This thesis is concerned with how the boundary clusters interact with each other according to that measure. One question that it considers are "how likely are these clusters to repel each other or to connect with one another in a certain topological configuration?" Chapter one non-rigorously derives an already well-known elliptic system of differential equations closely tied to this matter by using standard techniques of CFT, chapters two and three rigorously infer certain properties concerning the solution space of this system, and chapter four uses some of those results to predict an answer to this question. This thesis also considers local variations of this question such as "what regions of the domain do the perimeters of the boundary clusters explore," and "how often will several boundary clusters connect at just a single, specified point in the domain?" Chapter five predicts precise answers to these questions. All of these answers are quantitative predictions that we verify via high-precision computer simulation. Chapters four and five also present these simulation results. Further material that supplements chapter one is included in two appendices.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy.

PubMed

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-11-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929-1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

PubMed Central

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-01-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929–1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy. PMID:22915782

gWEGA: GPU-accelerated WEGA for molecular superposition and shape comparison.

PubMed

Yan, Xin; Li, Jiabo; Gu, Qiong; Xu, Jun

2014-06-05

Virtual screening of a large chemical library for drug lead identification requires searching/superimposing a large number of three-dimensional (3D) chemical structures. This article reports a graphic processing unit (GPU)-accelerated weighted Gaussian algorithm (gWEGA) that expedites shape or shape-feature similarity score-based virtual screening. With 86 GPU nodes (each node has one GPU card), gWEGA can screen 110 million conformations derived from an entire ZINC drug-like database with diverse antidiabetic agents as query structures within 2 s (i.e., screening more than 55 million conformations per second). The rapid screening speed was accomplished through the massive parallelization on multiple GPU nodes and rapid prescreening of 3D structures (based on their shape descriptors and pharmacophore feature compositions). Copyright © 2014 Wiley Periodicals, Inc.

Methods and devices for fabricating three-dimensional nanoscale structures

DOEpatents

Rogers, John A.; Jeon, Seokwoo; Park, Jangung

2010-04-27

The present invention provides methods and devices for fabricating 3D structures and patterns of 3D structures on substrate surfaces, including symmetrical and asymmetrical patterns of 3D structures. Methods of the present invention provide a means of fabricating 3D structures having accurately selected physical dimensions, including lateral and vertical dimensions ranging from 10s of nanometers to 1000s of nanometers. In one aspect, methods are provided using a mask element comprising a conformable, elastomeric phase mask capable of establishing conformal contact with a radiation sensitive material undergoing photoprocessing. In another aspect, the temporal and/or spatial coherence of electromagnetic radiation using for photoprocessing is selected to fabricate complex structures having nanoscale features that do not extend entirely through the thickness of the structure fabricated.

9-(3,4-Dimeth-oxy-phen-yl)-3,3,6,6-tetra-methyl-4,5,6,9-tetra-hydro-3H-xanthene-1,8(2H,7H)-dione.

PubMed

Mehdi, Sayed Hasan; Sulaiman, Othman; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-07-01

The asymmetric unit of the title xanthene compound, C(25)H(30)O(5), contains two mol-ecules in which the pyran ring and the dimeth-oxy-phenyl ring are nearly perpendicular to one another [dihedral angles = 86.81 (8) and 84.45 (9)°]. One of the meth-oxy groups in one mol-ecule is twisted away from the phenyl ring [C-O-C-C torsion angle = -103.40 (16)°]. The pyran ring adopts a boat conformation whereas the two fused cyclo-hexane rings adopt envelope conformations in both mol-ecules. In the crystal, mol-ecules are linked into a three-dimensional network by C-H⋯O hydrogen bonds.

Conformation-dependent recognition of a protein by T-lymphocytes: apomyoglobin-specific T-cell clone recognizes conformational changes between apomyoglobin and myoglobin

NASA Technical Reports Server (NTRS)

Cohly, H. H.; Morrison, D. R.; Atassi, M. Z.

1988-01-01

A T-cell clone specific to apomyoglobin was generated. It was prepared from a T-cell culture obtained by in vitro driving of lymph node cells with apomyoglobin from SJL mice that have been primed in vivo with apomyoglobin. In proliferative assays, the T-cell clone responded to apomyoglobin but did not recognize native myoglobin or any of the synthetic peptides corresponding to the six T sites of myoglobin. The demonstration that a T-cell clone can be isolated, whose specificity is directed entirely to apomyoglobin and not to its counterpart myoglobin, with an identical amino acid composition, indicates the importance of the three-dimensional structure in the presentation of the protein to T cells.

NIAS-Server: Neighbors Influence of Amino acids and Secondary Structures in Proteins.

PubMed

Borguesan, Bruno; Inostroza-Ponta, Mario; Dorn, Márcio

2017-03-01

The exponential growth in the number of experimentally determined three-dimensional protein structures provide a new and relevant knowledge about the conformation of amino acids in proteins. Only a few of probability densities of amino acids are publicly available for use in structure validation and prediction methods. NIAS (Neighbors Influence of Amino acids and Secondary structures) is a web-based tool used to extract information about conformational preferences of amino acid residues and secondary structures in experimental-determined protein templates. This information is useful, for example, to characterize folds and local motifs in proteins, molecular folding, and can help the solution of complex problems such as protein structure prediction, protein design, among others. The NIAS-Server and supplementary data are available at http://sbcb.inf.ufrgs.br/nias .

Analysis of Cytochrome P450 CYP119 Ligand-dependent Conformational Dynamics by Two-dimensional NMR and X-ray Crystallography*

PubMed Central

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

2015-01-01

Defining the conformational states of cytochrome P450 active sites is critical for the design of agents that minimize drug-drug interactions, the development of isoform-specific P450 inhibitors, and the engineering of novel oxidative catalysts. We used two-dimensional 1H,15N HSQC chemical shift perturbation mapping of 15N-labeled Phe residues and x-ray crystallography to examine the ligand-dependent conformational dynamics of CYP119. Active site Phe residues were most affected by the binding of azole inhibitors and fatty acid substrates, in agreement with active site localization of the conformational changes. This was supported by crystallography, which revealed movement of the F-G loop with various azoles. Nevertheless, the NMR chemical shift perturbations caused by azoles and substrates were distinguishable. The absence of significant chemical shift perturbations with several azoles revealed binding of ligands to an open conformation similar to that of the ligand-free state. In contrast, 4-phenylimidazole caused pronounced NMR changes involving Phe-87, Phe-144, and Phe-153 that support the closed conformation found in the crystal structure. The same closed conformation is observed by NMR and crystallography with a para-fluoro substituent on the 4-phenylimidazole, but a para-chloro or bromo substituent engendered a second closed conformation. An open conformation is thus favored in solution with many azole ligands, but para-substituted phenylimidazoles give rise to two closed conformations that depend on the size of the para-substituent. The results suggest that ligands selectively stabilize discrete cytochrome P450 conformational states. PMID:25670859

Critical solutions of topologically gauged = 8 CFTs in three dimensions

NASA Astrophysics Data System (ADS)

Nilsson, Bengt E. W.

2014-04-01

In this paper we discuss some special (critical) background solutions that arise in topological gauged = 8 three-dimensional CFTs with SO(N) gauge group. Depending on how many scalar fields are given a VEV the theory has background solutions for certain values of μl, where μ and l are parameters in the TMG Lagrangian. Apart from Minkowski, chiral round AdS 3 and null-warped AdS 3 (or Schrödinger( z = 2)) we identify also a more exotic solution recently found in TMG by Ertl, Grumiller and Johansson. We also discuss the spectrum, symmetry breaking pattern and the supermultiplet structure in the various backgrounds and argue that some properties are due to their common origin in a conformal phase. Some of the scalar fields, including all higgsed ones, turn out to satisfy three-dimensional field equations similar to those of the singleton. Finally, we note that topologically gauged = 6 ABJ(M) theories have a similar, but more restricted, set of background solutions.

Initial Results from the Royal College of Radiologists' UK National Audit of Anal Cancer Radiotherapy 2015.

PubMed

Muirhead, R; Drinkwater, K; O'Cathail, S M; Adams, R; Glynne-Jones, R; Harrison, M; Hawkins, M A; Sebag-Montefiore, D; Gilbert, D C

2017-03-01

UK guidance was recently developed for the treatment of anal cancer using intensity-modulated radiotherapy (IMRT). We audited the current use of radiotherapy in UK cancer centres for the treatment of anal cancer against such guidance. We describe the acute toxicity of IMRT in comparison with patient population in the audit treated with two-phase conformal radiotherapy and the previous published data from two-phase conformal radiotherapy, in the UK ACT2 trial. A Royal College of Radiologists' prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 6 month period between February and July 2015. Two hundred and forty-two cases were received from 40/56 cancer centres (71%). In total, 231 (95%) underwent full dose radiotherapy with prophylactic nodal irradiation. Of these, 180 (78%) received IMRT or equivalent, 52 (22%) two-phase conformal (ACT2) technique. The number of interruptions in radiotherapy treatment in the ACT2 trial was 15%. Interruptions were noted in 7% (95% confidence interval 0-14%) of courses receiving two-phase conformal and 4% (95% confidence interval 1-7%) of those receiving IMRT. The percentage of patients completing the planned radiotherapy dose, irrelevant of gaps, was 90% (95% confidence interval 82-98%) and 96% (95% confidence interval 93-99%), in two-phase conformal and IMRT respectively. The toxicity reported in the ACT2 trial, in patients receiving two-phase conformal in the audit and in patients receiving IMRT in the audit was: any toxic effect 71%, 54%, 48%, non-haematological 62%, 49%, 40% and haematological 26%, 13%, 18%, respectively. IMRT implementation for anal cancer is well underway in the UK with most patients receiving IMRT delivery, although its usage is not yet universal. This audit confirms that IMRT results in reduced acute toxicity and minimised treatment interruptions in comparison with previous two-phase conformal techniques. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer.

PubMed

McDermott, Ronan L; Armstrong, John G; Thirion, Pierre; Dunne, Mary; Finn, Marie; Small, Cormac; Byrne, Mary; O'Shea, Carmel; O'Sullivan, Lydia; Shannon, Aoife; Kelly, Emma; Hacking, Dayle J

2018-05-01

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis. Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatment plans sought to minimise oesophageal dose. Oesophagitis was recorded during treatment, at two weeks, one month and three months following radiation therapy and 3-6 monthly thereafter. Mean dose to the irradiated oesophagus was calculated for all treatment plans. Five patients (14%) had experienced grade 2 oesophagitis or dysphagia or both during treatment and 2 other patients had these side effects at the 2-week follow-up. At follow-up of one month after therapy, there was no grade two or higher oesophagitis or dysphagia reported. 22 patients were eligible for assessment of late toxicity. Five of these patients reported oesophagitis or dysphagia (one had grade 3 dysphagia, two had grade 2 oesophagitis, one of whom also had grade 2 dysphagia). Quality of Life (QoL) data at baseline and at 1-month follow up were available for 20 patients. At 1-month post radiation therapy, these patients had slightly less trouble taking a short walk, less shortness of breath, did not feel as weak, had better appetite and generally had a better overall quality of life than they did at baseline. They did report being slightly more tired. This trial is the first of its kind showing that 3-DCRT provides patients with lower rates of oesophageal toxicity whilst yielding acceptable rates of symptom control. (Sponsored by Cancer Trials Ireland (ICORG) Study number 06-34, the Friends of St. Luke's and the St. Luke's Institute of Cancer Research.). Copyright © 2018 Elsevier B.V. All rights reserved.

Modeling and analysis of visual digital impact model for a Chinese human thorax.

PubMed

Zhu, Jin; Wang, Kai-Ming; Li, Shu; Liu, Hai-Yan; Jing, Xiao; Li, Xiao-Fang; Liu, Yi-He

2017-01-01

To establish a three-dimensional finite element model of the human chest for engineering research on individual protection. Computed tomography (CT) scanning data were used for three-dimensional reconstruction with the medical image reconstruction software Mimics. The finite element method (FEM) preprocessing software ANSYS ICEM CFD was used for cell mesh generation, and the relevant material behavior parameters of all of the model's parts were specified. The finite element model was constructed with the FEM software, and the model availability was verified based on previous cadaver experimental data. A finite element model approximating the anatomical structure of the human chest was established, and the model's simulation results conformed to the results of the cadaver experiment overall. Segment data of the human body and specialized software can be utilized for FEM model reconstruction to satisfy the need for numerical analysis of shocks to the human chest in engineering research on body mechanics.

Multiscale modeling of three-dimensional genome

NASA Astrophysics Data System (ADS)

Zhang, Bin; Wolynes, Peter

The genome, the blueprint of life, contains nearly all the information needed to build and maintain an entire organism. A comprehensive understanding of the genome is of paramount interest to human health and will advance progress in many areas, including life sciences, medicine, and biotechnology. The overarching goal of my research is to understand the structure-dynamics-function relationships of the human genome. In this talk, I will be presenting our efforts in moving towards that goal, with a particular emphasis on studying the three-dimensional organization, the structure of the genome with multi-scale approaches. Specifically, I will discuss the reconstruction of genome structures at both interphase and metaphase by making use of data from chromosome conformation capture experiments. Computationally modeling of chromatin fiber at atomistic level from first principles will also be presented as our effort for studying the genome structure from bottom up.

Insights into the selective binding and toxic mechanism of microcystin to catalase

NASA Astrophysics Data System (ADS)

Hu, Yuandong; Da, Liangjun

2014-03-01

Microcystin is a sort of cyclic nonribosomal peptides produced by cyanobacteria. It is cyanotoxin, which can be very toxic for plants and animals including humans. The present study evaluated the interaction of microcystin and catalase, under physiological conditions by means of fluorescence, three-dimensional (3D) fluorescence, circular dichroism (CD), Fourier Transform infrared (FT-IR) spectroscopy, and enzymatic reactionkinetic techniques. The fluorescence data showed that microcystin could bind to catalase to form a complex. The binding process was a spontaneous molecular interaction procedure, in which electrostatic interactions played a major role. Energy transfer and fluorescence studies proved the existence of a static binding process. Additionally, as shown by the three-dimensional fluorescence, CD and FT-IR results, microcystin could lead to conformational and microenvironmental changes of the protein, which may affect the physiological functions of catalase. The work provides important insights into the toxicity mechanism of microcystin in vivo.

Stretchable ultrasonic transducer arrays for three-dimensional imaging on complex surfaces

PubMed Central

Zhu, Xuan; Li, Xiaoshi; Chen, Zeyu; Chen, Yimu; Lei, Yusheng; Li, Yang; Nomoto, Akihiro; Zhou, Qifa; di Scalea, Francesco Lanza

2018-01-01

Ultrasonic imaging has been implemented as a powerful tool for noninvasive subsurface inspections of both structural and biological media. Current ultrasound probes are rigid and bulky and cannot readily image through nonplanar three-dimensional (3D) surfaces. However, imaging through these complicated surfaces is vital because stress concentrations at geometrical discontinuities render these surfaces highly prone to defects. This study reports a stretchable ultrasound probe that can conform to and detect nonplanar complex surfaces. The probe consists of a 10 × 10 array of piezoelectric transducers that exploit an “island-bridge” layout with multilayer electrodes, encapsulated by thin and compliant silicone elastomers. The stretchable probe shows excellent electromechanical coupling, minimal cross-talk, and more than 50% stretchability. Its performance is demonstrated by reconstructing defects in 3D space with high spatial resolution through flat, concave, and convex surfaces. The results hold great implications for applications of ultrasound that require imaging through complex surfaces. PMID:29740603

Three-dimensional tertiary structure of yeast phenylalanine transfer RNA

NASA Technical Reports Server (NTRS)

Kim, S. H.; Sussman, J. L.; Suddath, F. L.; Quigley, G. J.; Mcpherson, A.; Wang, A. H. J.; Seeman, N. C.; Rich, A.

1974-01-01

Results of an analysis and interpretation of a 3-A electron density map of yeast phenylalanine transfer RNA. Some earlier detailed assignments of nucleotide residues to electron density peaks are found to be in error, even though the overall tracing of the backbone conformation of yeast phenylalanine transfer RNA was generally correct. A new, more comprehensive interpretation is made which makes it possible to define the tertiary interactions in the molecule. The new interpretation makes it possible to visualize a number of tertiary interactions which not only explain the structural role of most of the bases which are constant in transfer RNAs, but also makes it possible to understand in a direct and simple fashion the chemical modification data on transfer RNA. In addition, this pattern of tertiary interactions provides a basis for understanding the general three-dimensional folding of all transfer RNA molecules.

Three-dimensional structure and dynamics of wine tannin-saliva protein complexes. A multitechnique approach.

PubMed

Simon, Cécile; Barathieu, Karine; Laguerre, Michel; Schmitter, Jean-Marie; Fouquet, Eric; Pianet, Isabelle; Dufourc, Erick J

2003-09-09

The interactions between the B3 (catechin-4alpha,8-catechin) red wine tannin and the human salivary protein fragment IB7(14) (SPPGKPQGPPPQGG) were monitored by (1)H magic angle spinning NMR, circular dichroism, electrospray ionization mass spectrometry, and molecular modeling. It is found that the secondary structure of IB7(14) is made of a type II helix (collagen helix) and random coil. The central glycine 8 appears to act as a flexible rotula separating two helix II regions. Three tannin molecules tightly complex the peptide, without modifying its secondary structure, but seem to reduce its conformational dynamics. The binding dissociation constant is in the millimolar range. B3 tannins with a "tweezers" conformation bind to the hydrophilic side of the saliva peptide, suggesting that the principal driving forces toward association are governed by hydrogen bonding between the carbonyl functions of proline residues and both the phenol and catechol OH groups. These findings are further discussed in the frame of an astringency phenomenon.

Conformal Robotic Stereolithography

PubMed Central

Stevens, Adam G.; Oliver, C. Ryan; Kirchmeyer, Matthieu; Wu, Jieyuan; Chin, Lillian; Polsen, Erik S.; Archer, Chad; Boyle, Casey; Garber, Jenna

2016-01-01

Abstract Additive manufacturing by layerwise photopolymerization, commonly called stereolithography (SLA), is attractive due to its high resolution and diversity of materials chemistry. However, traditional SLA methods are restricted to planar substrates and planar layers that are perpendicular to a single-axis build direction. Here, we present a robotic system that is capable of maskless layerwise photopolymerization on curved surfaces, enabling production of large-area conformal patterns and the construction of conformal freeform objects. The system comprises an industrial six-axis robot and a custom-built maskless projector end effector. Use of the system involves creating a mesh representation of the freeform substrate, generation of a triangulated toolpath with curved layers that represents the target object to be printed, precision mounting of the substrate in the robot workspace, and robotic photopatterning of the target object by coordinated motion of the robot and substrate. We demonstrate printing of conformal photopatterns on spheres of various sizes, and construction of miniature three-dimensional objects on spheres without requiring support features. Improvement of the motion accuracy and development of freeform toolpaths would enable construction of polymer objects that surpass the size and support structure constraints imparted by traditional SLA systems. PMID:29577062

Avalanche for shape and feature-based virtual screening with 3D alignment

NASA Astrophysics Data System (ADS)

Diller, David J.; Connell, Nancy D.; Welsh, William J.

2015-11-01

This report introduces a new ligand-based virtual screening tool called Avalanche that incorporates both shape- and feature-based comparison with three-dimensional (3D) alignment between the query molecule and test compounds residing in a chemical database. Avalanche proceeds in two steps. The first step is an extremely rapid shape/feature based comparison which is used to narrow the focus from potentially millions or billions of candidate molecules and conformations to a more manageable number that are then passed to the second step. The second step is a detailed yet still rapid 3D alignment of the remaining candidate conformations to the query conformation. Using the 3D alignment, these remaining candidate conformations are scored, re-ranked and presented to the user as the top hits for further visualization and evaluation. To provide further insight into the method, the results from two prospective virtual screens are presented which show the ability of Avalanche to identify hits from chemical databases that would likely be missed by common substructure-based or fingerprint-based search methods. The Avalanche method is extended to enable patent landscaping, i.e., structural refinements to improve the patentability of hits for deployment in drug discovery campaigns.

Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function.

PubMed

Väre, Ville Y P; Eruysal, Emily R; Narendran, Amithi; Sarachan, Kathryn L; Agris, Paul F

2017-03-16

RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA's cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.

New potentials for conformal mechanics

NASA Astrophysics Data System (ADS)

Papadopoulos, G.

2013-04-01

We find under some mild assumptions that the most general potential of one-dimensional conformal systems with time-independent couplings is expressed as V = V0 + V1, where V0 is a homogeneous function with respect to a homothetic motion in configuration space and V1 is determined from an equation with source a homothetic potential. Such systems admit at most an SL(2,{R}) conformal symmetry which, depending on the couplings, is embedded in {Diff}({R}) in three different ways. In one case, SL(2,{R}) is also embedded in Diff(S1). Examples of such models include those with potential V = αx2 + βx-2 for arbitrary couplings α and β, the Calogero models with harmonic oscillator couplings and nonlinear models with suitable metrics and potentials. In addition, we give the conditions on the couplings for a class of gauge theories to admit a SL(2,{R}) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries that include the isometries of AdS2 × S3 and AdS2 × S3 × S3 which arise as backgrounds in AdS2/CFT1.

Renyi entropy for local quenches in 2D CFT from numerical conformal blocks

NASA Astrophysics Data System (ADS)

Kusuki, Yuya; Takayanagi, Tadashi

2018-01-01

We study the time evolution of Renyi entanglement entropy for locally excited states in two dimensional large central charge CFTs. It generically shows a logarithmical growth and we compute the coefficient of log t term. Our analysis covers the entire parameter regions with respect to the replica number n and the conformal dimension h O of the primary operator which creates the excitation. We numerically analyse relevant vacuum conformal blocks by using Zamolodchikov's recursion relation. We find that the behavior of the conformal blocks in two dimensional CFTs with a central charge c, drastically changes when the dimensions of external primary states reach the value c/32. In particular, when h O ≥ c/32 and n ≥ 2, we find a new universal formula Δ {S}_A^{(n)}˜eq nc/24(n-1) log t. Our numerical results also confirm existing analytical results using the HHLL approximation.

Reduced toxicity with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy compared with conventional two-dimensional radiotherapy for esophageal squamous cell carcinoma: a secondary analysis of data from four prospective clinical trials.

PubMed

Deng, J-Y; Wang, C; Shi, X-H; Jiang, G-L; Wang, Y; Liu, Y; Zhao, K-L

2016-11-01

We conducted a retrospective analysis to assess the toxicity and long-term survival of esophageal squamous cell carcinoma patients treated with three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2DRT). All data in the present study were based on four prospective clinical trials conducted at our institution from 1996 to 2004 and included 308 esophageal squamous cell carcinoma patients treated with 2DRT or 3DCRT/IMRT. Based on the inclusion and exclusion criteria, 254 patients were included in the analysis. Of these patients, 158 were treated with 2DRT, whereas 96 were treated with 3DCRT/IMRT. The rates of ≥Grade3 acute toxicity of the esophagus and lung were 11.5% versus 28.5% (P = 0.002) and 5.2% versus 10.8% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The incidences of ≥Grade 3 late toxicity of the esophagus and lungs were 3.1% versus 10.7% (P = 0.028) and 3.1% versus 5.7% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The 1-year, 3-year and 5-year estimated overall survival rates were 81%, 38% and 34% in the 3DCRT/IMRT group and 79%, 44% and 31% in the 2DRT group, respectively (P = 0.628). The 1-year, 3-year and 5-year local control rates were 88%, 71% and 66% in the 3DCRT/IMRT group and 84%, 66% and 60% in the 2DRT group, respectively (P = 0.412). Fewer incidences of acute and late toxicities were observed in esophageal squamous cell carcinoma patients treated with 3DCRT/IMRT compared with those treated with 2DRT. No significant survival benefit was observed with the use of 3DCRT/IMRT. © 2015 International Society for Diseases of the Esophagus.

Prostate Bed Motion During Intensity-Modulated Radiotherapy Treatment

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

Klayton, Tracy; Price, Robert; Buyyounouski, Mark K.

Purpose: Conformal radiation therapy in the postprostatectomy setting requires accurate setup and localization of the prostatic fossa. In this series, we report prostate bed localization and motion characteristics, using data collected from implanted radiofrequency transponders. Methods and Materials: The Calypso four-dimensional localization system uses three implanted radiofrequency transponders for daily target localization and real-time tracking throughout a course of radiation therapy. We reviewed the localization and tracking reports for 20 patients who received ultrasonography-guided placement of Calypso transponders within the prostate bed prior to a course of intensity-modulated radiation therapy at Fox Chase Cancer Center. Results: At localization, prostate bedmore » displacement relative to bony anatomy exceeded 5 mm in 9% of fractions in the anterior-posterior (A-P) direction and 21% of fractions in the superior-inferior (S-I) direction. The three-dimensional vector length from skin marks to Calypso alignment exceeded 1 cm in 24% of all 652 fractions with available setup data. During treatment, the target exceeded the 5-mm tracking limit for at least 30 sec in 11% of all fractions, generally in the A-P or S-I direction. In the A-P direction, target motion was twice as likely to move posteriorly, toward the rectum, than anteriorly. Fifteen percent of all treatments were interrupted for repositioning, and 70% of patients were repositioned at least once during their treatment course. Conclusion: Set-up errors and motion of the prostatic fossa during radiotherapy are nontrivial, leading to potential undertreatment of target and excess normal tissue toxicity if not taken into account during treatment planning. Localization and real-time tracking of the prostate bed via implanted Calypso transponders can be used to improve the accuracy of plan delivery.« less

Conformal flight path symbology for head-up displays: Defining the distribution of visual attention in three-dimensional space

NASA Astrophysics Data System (ADS)

Ververs, Patricia May

An extensive investigation of the format for head-up display (HUD) instrumentation was conducted in a two-part experiment. First, a pilot's information requirements for the tasks of approach, landing, and taxi were determined through a survey administered to professional commercial pilots via the world wide web. The results of the survey were applied in the development of two symbology sets, one set for flight navigation and the second for ground navigation. Second, twenty pilots from the University of Illinois at Urbana-Champaign were recruited to participate in a 3-day experiment. The study was designed to investigate the format for symbology on HUDs and the performance effects of using conformal and partially conformal symbology to support the pilots' tasks. In addition, two different methods were investigated for supporting the pilots' transition between the task of flying and the task of landing. A seamless transition used visual momentum techniques to smoothly guide the pilots' cognitive transition between the serial displays and the associated tasks. A seamed approach employed an abrupt change between the displays to alert the pilots of the task switch. The results indicate that incorporating a virtually conformal, tunnel-in-the-sky symbology into a complete HUD instrumentation set offers promising pilot performance effects. Pilots easily navigated the complex curved approaches with little to no deviation from the flight path (approximately 10 feet), while performing the secondary tasks of the scanning their instruments and the environment. The seamless transition between the flight and ground symbology offered the pilots a preview of the upcoming landing task, thereby preparing them for the task switch. On the ground, the perspective (scene-linked) symbology set supported landing and taxi navigation tasks with the equal efficiency to the plan view display but with much greater precision. Theories of allocation of attention were used to interpret the experimental findings. Attention was found to be more widely distributed in X-Y space when the pilots were flying with the conformal, tunnel-in-the-sky as compared to the partially conformal ILS (instrument landing system) symbology set. There was little evidence that the air-based navigation displays were supporting divided attention in three-dimensional space. The ground-based scene-linked (truly conformal) display indicated promising effects of dividing attention in depth without negative consequences to processing the near domain symbology. Event expectancy was found to modulate pilot performance in the detection of events both on the symbology and in the environment. The phenomenon known as cognitive tunneling is discussed as a possible cause of the inadequate response times in resolving the anomalous events.

Structural consequences of metallothionein dimerization: solution structure of the isolated Cd4-alpha-domain and comparison with the holoprotein dimer.

PubMed

Ejnik, John W; Muñoz, Amalia; DeRose, Eugene; Shaw, C Frank; Petering, David H

2003-07-22

The NMR determination of the structure of Cd(7)-metallothionein was done previously using a relatively large protein concentration that favors dimer formation. The reactivity of the protein is also affected under this condition. To examine the influence of protein concentration on metallothionein conformation, the isolated Cd(4)-alpha-domain was prepared from rabbit metallothionein-2 (MT 2), and its three-dimensional structure was determined by heteronuclear, (1)H-(111)Cd, and homonuclear, (1)H-(1)H NMR, correlation experiments. The three-dimensional structure was refined using distance and angle constraints derived from these two-dimensional NMR data sets and a distance geometry/simulated annealing protocol. The backbone superposition of the alpha-domain from rabbit holoprotein Cd(7)-MT 2 and the isolated rabbit Cd(4)-alpha was measured at a RMSD of 2.0 A. Nevertheless, the conformations of the two Cd-thiolate clusters were distinctly different at two of the cadmium centers. In addition, solvent access to the sulfhydryl ligands of the isolated Cd(4)-alpha cluster was 130% larger due to this small change in cluster geometry. To probe whether these differences were an artifact of the structure calculation, the Cd(4)-alpha-domain structure in rabbit Cd(7)-MT 2 was redetermined, using the previously defined set of NOEs and the present calculation protocol. All calculations employed the same ionic radius for Cd(2+) and same cadmium-thiolate bond distance. The newly calculated structure matched the original with an RMSD of 1.24 A. It is hypothesized that differences in the two alpha-domain structures result from a perturbation of the holoprotein structure because of head-to-tail dimerization under the conditions of the NMR experiments.

Coulomb branch operators and mirror symmetry in three dimensions

NASA Astrophysics Data System (ADS)

Dedushenko, Mykola; Fan, Yale; Pufu, Silviu S.; Yacoby, Ran

2018-04-01

We develop new techniques for computing exact correlation functions of a class of local operators, including certain monopole operators, in three-dimensional N=4 abelian gauge theories that have superconformal infrared limits. These operators are position-dependent linear combinations of Coulomb branch operators. They form a one-dimensional topological sector that encodes a deformation quantization of the Coulomb branch chiral ring, and their correlation functions completely fix the ( n ≤ 3)-point functions of all half-BPS Coulomb branch operators. Using these results, we provide new derivations of the conformal dimension of half-BPS monopole operators as well as new and detailed tests of mirror symmetry. Our main approach involves supersymmetric localization on a hemisphere HS 3 with half-BPS boundary conditions, where operator insertions within the hemisphere are represented by certain shift operators acting on the HS 3 wavefunction. By gluing a pair of such wavefunctions, we obtain correlators on S 3 with an arbitrary number of operator insertions. Finally, we show that our results can be recovered by dimensionally reducing the Schur index of 4D N=2 theories decorated by BPS 't Hooft-Wilson loops.

Approximating gecko setae via direct laser lithography

NASA Astrophysics Data System (ADS)

Tricinci, Omar; Eason, Eric V.; Filippeschi, Carlo; Mondini, Alessio; Mazzolai, Barbara; Pugno, Nicola M.; Cutkosky, Mark R.; Greco, Francesco; Mattoli, Virgilio

2018-07-01

The biomimetic replication of dry adhesion present in the gecko’s foot has attracted great interest in recent years. All the microfabrication techniques used so far were not able to faithfully reproduce the hierarchical and complex three-dimensional geometry of the gecko’s setae, with features at the micro- and nano-scale, thus reducing the effectiveness that such conformal morphology could provide. By means of direct laser lithography we fabricated artificial hairs that faithfully reproduce the natural model. This technique allows the fabrication of three-dimensional microstructures with outstanding results in terms of reproducibility and resolution at the micro- and nano-scale. It was possible to get very close to the morphology of the natural gecko setae, especially concerning the hierarchical shape. We designed several morphologies for the setae and studied the effects in terms of adhesion and friction performances compared to the natural counterpart, showing the interplay between morphology, dimensional scaling and materials. Direct laser lithography promises great applications in the biomimetics field, paving the way to the implementation of the concept of hierarchical bioinspired dry adhesives.

Multiple steady solutions in a driven cavity

NASA Astrophysics Data System (ADS)

Osman, Kahar; McHugh, John

2004-11-01

The symmetric driven cavity (Farias and McHugh, Phys. Fluids, 2002) in two and three dimensions is considered. Results are obtained via numerical computations of the Navier-Stokes equations, assuming constant density. The numerical algorithm is a splitting method, using finite differences. The forcing at the top is sinusoidal, and the forcing wavelength is allowed to vary in subsequent trials. The two dimensional results with 2, 4, and 6 oscillations in the forcing show a subcritical bifurcation to an asymmetric solution, with the Reynolds number as the important parameter. The symmetric solution is found to have vortex flow with streamlines that conform to the boundary shape. The asymmetric solution has vortex flow with streamlines that are approximately circular near the vortex center. Two dimensional results with 8 or more oscillations in the forcing show a supercritical bifurcation to an asymmetric solution. Three dimensional simulations show that the length ratios play a critical role, and the depth of the cavity must be large compared to the height in order to acheive the same subcritical bifurcation as with two dimensions.

Non-singular spacetimes with a negative cosmological constant: IV. Stationary black hole solutions with matter fields

NASA Astrophysics Data System (ADS)

Chruściel, Piotr T.; Delay, Erwann; Klinger, Paul

2018-02-01

We use an elliptic system of equations with complex coefficients for a set of complex-valued tensor fields as a tool to construct infinite-dimensional families of non-singular stationary black holes, real-valued Lorentzian solutions of the Einstein–Maxwell-dilaton-scalar fields-Yang–Mills–Higgs–Chern–Simons-f(R) equations with a negative cosmological constant. The families include an infinite-dimensional family of solutions with the usual AdS conformal structure at conformal infinity.

Structural determination of nanomolar quantities of neuroactive peptides by nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Matei, Elena

The specificity of the conotoxin is one of the attributes that make them a valuable diagnostic tool in the characterization of neuronal mechanisms, or therapeutic agents in medicine. It appears that Nature has provided us with a pharmaceutical tool in the form of Conus peptides. Further studies will only enhance our understanding, and use, of these molecules in medicine and science. The study of three-dimensional structure in relation to the function of cone snail peptides is an area of increasing interest. The venom of a single cone snail can contain as many as 300 different chemical components. Individual cone snail venom components, or conopeptides, can have powerful neurological effects. For many interesting species, not enough venom collected from the natural origin is available for experimental investigations. After a laborious separation procedure, only nanomole quantities of these native conopeptides are able to be obtained. Therefore, several experimental applications, such as NMR spectroscopy, are difficult to carry out using traditional methods. The research was focused on using nanoNMR spectroscopy as an alternative method to the conventional NMR spectroscopy method in order to analyze small quantities of novel peptides with unknown three-dimensional conformational arrangement. The experimental results obtained using the HR-MAS NMR technique, in addition to the use of a 3mm gHCN (with 1.7mm inserts) NMR probes, proved the capability of conformational analysis of different types of natural products at sample levels down to nanomole range. Understanding the interaction between agonist or antagonist ligands and their target receptors, at a molecular level, offer promise for the development of pharmacological therapeutics for the central nervous system. Conopeptides are of great interest as ligands in neuroscience and are valuable leads in drug design, based on their specificity and potency for therapeutically relevant receptors and ion channels. For instance, the compound called Prialt (formerly known as Ziconotide), a synthetic form of a cone snail-derived peptide, is the most powerful painkiller known and has already received the Food and Drug Administration (FDA) approval. The drug is part of a new class known as the N-type calcium channel blockers, which are responsible for transmitting pain signals. Several related cone snail drugs are currently in clinical trials and could eventually be used to treat different diseases such as Alzheimer's, epilepsy and Parkinson's.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

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

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Use of restrained molecular dynamics to predict the conformations of phosphorylated receiver domains in two-component signaling systems.

PubMed

Foster, Clay A; West, Ann H

2017-01-01

Two-component signaling (TCS) is the primary means by which bacteria, as well as certain plants and fungi, respond to external stimuli. Signal transduction involves stimulus-dependent autophosphorylation of a sensor histidine kinase and phosphoryl transfer to the receiver domain of a downstream response regulator. Phosphorylation acts as an allosteric switch, inducing structural and functional changes in the pathway's components. Due to their transient nature, phosphorylated receiver domains are challenging to characterize structurally. In this work, we provide a methodology for simulating receiver domain phosphorylation to predict conformations that are nearly identical to experimental structures. Using restrained molecular dynamics, phosphorylated conformations of receiver domains can be reliably sampled on nanosecond timescales. These simulations also provide data on conformational dynamics that can be used to identify regions of functional significance related to phosphorylation. We first validated this approach on several well-characterized receiver domains and then used it to compare the upstream and downstream components of the fungal Sln1 phosphorelay. Our results demonstrate that this technique provides structural insight, obtained in the absence of crystallographic or NMR information, regarding phosphorylation-induced conformational changes in receiver domains that regulate the output of their associated signaling pathway. To our knowledge, this is the first time such a protocol has been described that can be broadly applied to TCS proteins for predictive purposes. Proteins 2016; 85:155-176. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

System and method to create three-dimensional images of non-linear acoustic properties in a region remote from a borehole

DOEpatents

Vu, Cung; Nihei, Kurt T.; Schmitt, Denis P.; Skelt, Christopher; Johnson, Paul A.; Guyer, Robert; TenCate, James A.; Le Bas, Pierre-Yves

2013-01-01

In some aspects of the disclosure, a method for creating three-dimensional images of non-linear properties and the compressional to shear velocity ratio in a region remote from a borehole using a conveyed logging tool is disclosed. In some aspects, the method includes arranging a first source in the borehole and generating a steered beam of elastic energy at a first frequency; arranging a second source in the borehole and generating a steerable beam of elastic energy at a second frequency, such that the steerable beam at the first frequency and the steerable beam at the second frequency intercept at a location away from the borehole; receiving at the borehole by a sensor a third elastic wave, created by a three wave mixing process, with a frequency equal to a difference between the first and second frequencies and a direction of propagation towards the borehole; determining a location of a three wave mixing region based on the arrangement of the first and second sources and on properties of the third wave signal; and creating three-dimensional images of the non-linear properties using data recorded by repeating the generating, receiving and determining at a plurality of azimuths, inclinations and longitudinal locations within the borehole. The method is additionally used to generate three dimensional images of the ratio of compressional to shear acoustic velocity of the same volume surrounding the borehole.

Near-horizon conformal symmetry and black hole entropy.

PubMed

Carlip, S

2002-06-17

Near an event horizon, the action of general relativity acquires a new asymptotic conformal symmetry. For two-dimensional dilaton gravity, this symmetry results in a chiral Virasoro algebra, and Cardy's formula for the density of states reproduces the Bekenstein-Hawking entropy. This lends support to the notion that black hole entropy is controlled universally by conformal symmetry near the horizon.

Aspects of Higher Spin Symmetry and its Breaking

NASA Astrophysics Data System (ADS)

Zhiboedov, Alexander

This thesis explores different aspects of higher spin symmetry and its breaking in the context of Quantum Field Theory, AdS/CFT and String Theory. In chapter 2, we study the constraints imposed by the existence of a single higher spin conserved current on a three-dimensional conformal field theory (CFT). A single higher spin conserved current implies the existence of an infinite number of higher spin conserved currents. The correlation functions of the stress tensor and the conserved currents are then shown to be equal to those of a free field theory. Namely a theory of N free bosons or free fermions. This is an extension of the Coleman-Mandula theorem to CFT's, which do not have a conventional S-matrix. In chapter 3, we consider three-dimensional conformal field theories that have a higher spin symmetry that is slightly broken. The theories have a large N limit, in the sense that the operators separate into single-trace and multi-trace and obey the usual large N factorization properties. We assume that the only single trace operators are the higher spin currents plus an additional scalar. Using the slightly broken higher spin symmetry we constrain the three-point functions of the theories to leading order in N. We show that there are two families of solutions. One family can be realized as a theory of N fermions with an O( N) Chern-Simons gauge field, the other as a N bosons plus the Chern-Simons gauge field. In chapter 4, we consider several aspects of unitary higher-dimensional conformal field theories. We investigate the dimensions of spinning operators via the crossing equations in the light-cone limit. We find that, in a sense, CFTs become free at large spin and 1/s is a weak coupling parameter. The spectrum of CFTs enjoys additivity: if two twists tau 1, tau2 appear in the spectrum, there are operators whose twists are arbitrarily close to tau1 + tau2. We characterize how tau1 + tau2 is approached at large spin by solving the crossing equations analytically. Applications include the 3d Ising model, theories with a gravity dual, SCFTs, and patterns of higher spin symmetry breaking. In chapter 5, we consider higher derivative corrections to the graviton three-point coupling within a weakly coupled theory of gravity. We devise a thought experiment involving a high energy scattering process which leads to causality violation if the graviton three-point vertex contains the additional structures. This violation cannot be fixed by adding conventional particles with spins J ≤ 2. But, it can be fixed by adding an infinite tower of extra massive particles with higher spins, J > 2. In AdS theories this implies a constraint on the conformal anomaly coefficients (a-c)/c lesssim 1/Delta gap2 in terms of Deltagap, the dimension of the lightest single particle operator with spin J > 2. For inflation, or de Sitter-like solutions, it indicates the existence of massive higher spin particles if the gravity wave non-gaussianity deviates significantly from the one computed in the Einstein theory.

An exact conformal symmetry Ansatz on Kaluza-Klein reduced TMG

NASA Astrophysics Data System (ADS)

Moutsopoulos, George; Ritter, Patricia

2011-11-01

Using a Kaluza-Klein dimensional reduction, and further imposing a conformal Killing symmetry on the reduced metric generated by the dilaton, we show an Ansatz that yields many of the known stationary axisymmetric solutions to TMG.

Critical excitation spectrum of a quantum chain with a local three-spin coupling.

PubMed

McCabe, John F; Wydro, Tomasz

2011-09-01

Using the phenomenological renormalization group (PRG), we evaluate the low-energy excitation spectrum along the critical line of a quantum spin chain having a local interaction between three Ising spins and longitudinal and transverse magnetic fields, i.e., a Turban model. The low-energy excitation spectrum found with the PRG agrees with the spectrum predicted for the (D(4),A(4)) conformal minimal model under a nontrivial correspondence between translations at the critical line and discrete lattice translations. Under this correspondence, the measurements confirm a prediction that the critical line of this quantum spin chain and the critical point of the two-dimensional three-state Potts model are in the same universality class.

A perspective on the primary and three-dimensional structures of carbohydrates.

PubMed

Widmalm, Göran

2013-08-30

Carbohydrates, in more biologically oriented areas referred to as glycans, constitute one of the four groups of biomolecules. The glycans, often present as glycoproteins or glycolipids, form highly complex structures. In mammals ten monosaccharides are utilized in building glycoconjugates in the form of oligo- (up to about a dozen monomers) and polysaccharides. Subsequent modifications and additions create a large number of different compounds. In bacteria, more than a hundred monosaccharides have been reported to be constituents of lipopolysaccharides, capsular polysaccharides, and exopolysaccharides. Thus, the number of polysaccharide structures possible to create is huge. NMR spectroscopy plays an essential part in elucidating the primary structure, that is, monosaccharide identity and ring size, anomeric configuration, linkage position, and sequence, of the sugar residues. The structural studies may also employ computational approaches for NMR chemical shift predictions (CASPER program). Once the components and sequence of sugar residues have been unraveled, the three-dimensional arrangement of the sugar residues relative to each other (conformation), their flexibility (transitions between and populations of conformational states), together with the dynamics (timescales) should be addressed. To shed light on these aspects we have utilized a combination of experimental liquid state NMR techniques together with molecular dynamics simulations. For the latter a molecular mechanics force field such as our CHARMM-based PARM22/SU01 has been used. The experimental NMR parameters acquired are typically (1)H,(1)H cross-relaxation rates (related to NOEs), (3)JCH and (3)JCCtrans-glycosidic coupling constants and (1)H,(13)C- and (1)H,(1)H-residual dipolar couplings. At a glycosidic linkage two torsion angles ϕ and ψ are defined and for 6-substituted residues also the ω torsion angle is required. Major conformers can be identified for which highly populated states are present. Thus, in many cases a well-defined albeit not rigid structure can be identified. However, on longer timescales, oligosaccharides must be considered as highly flexible molecules since also anti-conformations have been shown to exist with H-C-O-C torsion angles of ∼180°, compared to syn-conformations in which the protons at the carbon atoms forming the glycosidic linkage are in close proximity. The accessible conformational space governs possible interactions with proteins and both minor changes and significant alterations occur for the oligosaccharides in these interaction processes. Transferred NOE NMR experiments give information on the conformation of the glycan ligand when bound to the proteins whereas saturation transfer difference NMR experiments report on the carbohydrate part in contact with the protein. It is anticipated that the subtle differences in conformational preferences for glycan structures facilitate a means to regulate biochemical processes in different environments. Further developments in the analysis of glycan structure and in particular its role in interactions with other molecules, will lead to clarifications of the importance of structure in biochemical regulation processes essential to health and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Online service for monitoring the ionosphere based on data from the global navigation satellite system

NASA Astrophysics Data System (ADS)

Aleshin, I. M.; Alpatov, V. V.; Vasil'ev, A. E.; Burguchev, S. S.; Kholodkov, K. I.; Budnikov, P. A.; Molodtsov, D. A.; Koryagin, V. N.; Perederin, F. V.

2014-07-01

A service is described that makes possible the effective construction of a three-dimensional ionospheric model based on the data of ground receivers of signals from global navigation satellite positioning systems (GNSS). The obtained image has a high resolution, mainly because data from the IPG GNSS network of the Federal Service for Hydrometeorology and Environmental Monitoring (Rosgidromet) are used. A specially developed format and its implementation in the form of SQL structures are used to collect, transmit, and store data. The method of high-altitude radio tomography is used to construct the three-dimensional model. The operation of all system components (from registration point organization to the procedure for constructing the electron density three-dimensional distribution and publication of the total electron content map on the Internet) has been described in detail. The three-dimensional image of the ionosphere, obtained automatically, is compared with the ionosonde measurements, calculated using the two-dimensional low-altitude tomography method and averaged by the ionospheric model.

Conformational Flexibility and Subunit Arrangement of the Modular Yeast Spt-Ada-Gcn5 Acetyltransferase Complex*

PubMed Central

Setiaputra, Dheva; Ross, James D.; Lu, Shan; Cheng, Derrick T.; Dong, Meng-Qiu; Yip, Calvin K.

2015-01-01

The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex is a highly conserved, 19-subunit histone acetyltransferase complex that activates transcription through acetylation and deubiquitination of nucleosomal histones in Saccharomyces cerevisiae. Because SAGA has been shown to display conformational variability, we applied gradient fixation to stabilize purified SAGA and systematically analyzed this flexibility using single-particle EM. Our two- and three-dimensional studies show that SAGA adopts three major conformations, and mutations of specific subunits affect the distribution among these. We also located the four functional modules of SAGA using electron microscopy-based labeling and transcriptional activator binding analyses and show that the acetyltransferase module is localized in the most mobile region of the complex. We further comprehensively mapped the subunit interconnectivity of SAGA using cross-linking mass spectrometry, revealing that the Spt and Taf subunits form the structural core of the complex. These results provide the necessary restraints for us to generate a model of the spatial arrangement of all SAGA subunits. According to this model, the chromatin-binding domains of SAGA are all clustered in one face of the complex that is highly flexible. Our results relate information of overall SAGA structure with detailed subunit level interactions, improving our understanding of its architecture and flexibility. PMID:25713136

Management of three-dimensional intrafraction motion through real-time DMLC tracking.

PubMed

Sawant, Amit; Venkat, Raghu; Srivastava, Vikram; Carlson, David; Povzner, Sergey; Cattell, Herb; Keall, Paul

2008-05-01

Tumor tracking using a dynamic multileaf collimator (DMLC) represents a promising approach for intrafraction motion management in thoracic and abdominal cancer radiotherapy. In this work, we develop, empirically demonstrate, and characterize a novel 3D tracking algorithm for real-time, conformal, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based radiation delivery to targets moving in three dimensions. The algorithm obtains real-time information of target location from an independent position monitoring system and dynamically calculates MLC leaf positions to account for changes in target position. Initial studies were performed to evaluate the geometric accuracy of DMLC tracking of 3D target motion. In addition, dosimetric studies were performed on a clinical linac to evaluate the impact of real-time DMLC tracking for conformal, step-and-shoot (S-IMRT), dynamic (D-IMRT), and VMAT deliveries to a moving target. The efficiency of conformal and IMRT delivery in the presence of tracking was determined. Results show that submillimeter geometric accuracy in all three dimensions is achievable with DMLC tracking. Significant dosimetric improvements were observed in the presence of tracking for conformal and IMRT deliveries to moving targets. A gamma index evaluation with a 3%-3 mm criterion showed that deliveries without DMLC tracking exhibit between 1.7 (S-IMRT) and 4.8 (D-IMRT) times more dose points that fail the evaluation compared to corresponding deliveries with tracking. The efficiency of IMRT delivery, as measured in the lab, was observed to be significantly lower in case of tracking target motion perpendicular to MLC leaf travel compared to motion parallel to leaf travel. Nevertheless, these early results indicate that accurate, real-time DMLC tracking of 3D tumor motion is feasible and can potentially result in significant geometric and dosimetric advantages leading to more effective management of intrafraction motion.

Structure of the extracellular domain of matrix protein 2 of influenza A virus in complex with a protective monoclonal antibody.

PubMed

Cho, Ki Joon; Schepens, Bert; Seok, Jong Hyeon; Kim, Sella; Roose, Kenny; Lee, Ji-Hye; Gallardo, Rodrigo; Van Hamme, Evelien; Schymkowitz, Joost; Rousseau, Frederic; Fiers, Walter; Saelens, Xavier; Kim, Kyung Hyun

2015-04-01

The extracellular domain of influenza A virus matrix protein 2 (M2e) is conserved and is being evaluated as a quasiuniversal influenza A vaccine candidate. We describe the crystal structure at 1.6 Å resolution of M2e in complex with the Fab fragment of an M2e-specific monoclonal antibody that protects against influenza A virus challenge. This antibody binds M2 expressed on the surfaces of cells infected with influenza A virus. Five out of six complementary determining regions interact with M2e, and three highly conserved M2e residues are critical for this interaction. In this complex, M2e adopts a compact U-shaped conformation stabilized in the center by the highly conserved tryptophan residue in M2e. This is the first description of the three-dimensional structure of M2e. M2e of influenza A is under investigation as a universal influenza A vaccine, but its three-dimensional structure is unknown. We describe the structure of M2e stabilized with an M2e-specific monoclonal antibody that recognizes natural M2. We found that the conserved tryptophan is positioned in the center of the U-shaped structure of M2e and stabilizes its conformation. The structure also explains why previously reported in vivo escape viruses, selected with a similar monoclonal antibody, carried proline residue substitutions at position 10 in M2. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach.

PubMed

Estrada, T; Zhang, B; Cicotti, P; Armen, R S; Taufer, M

2012-07-01

We present a scalable and accurate method for classifying protein-ligand binding geometries in molecular docking. Our method is a three-step process: the first step encodes the geometry of a three-dimensional (3D) ligand conformation into a single 3D point in the space; the second step builds an octree by assigning an octant identifier to every single point in the space under consideration; and the third step performs an octree-based clustering on the reduced conformation space and identifies the most dense octant. We adapt our method for MapReduce and implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in MapReduce allow screening of very large conformation spaces not approachable with traditional clustering methods. We analyze results for docking trials for 23 protein-ligand complexes for HIV protease, 21 protein-ligand complexes for Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze cross docking trials for 24 ligands, each docking into 24 protein conformations of the HIV protease, and receptor ensemble docking trials for 24 ligands, each docking in a pool of HIV protease receptors. Our method demonstrates significant improvement over energy-only scoring for the accurate identification of native ligand geometries in all these docking assessments. The advantages of our clustering approach make it attractive for complex applications in real-world drug design efforts. We demonstrate that our method is particularly useful for clustering docking results using a minimal ensemble of representative protein conformational states (receptor ensemble docking), which is now a common strategy to address protein flexibility in molecular docking. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

NASA Astrophysics Data System (ADS)

Qiao, Qin; Zhang, Hou-Dao; Huang, Xuhui

2016-04-01

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

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

Qiao, Qin, E-mail: qqiao@ust.hk; Zhang, Hou-Dao; Huang, Xuhui, E-mail: xuhuihuang@ust.hk

2016-04-21

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kineticsmore » are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.« less

A probabilistic and continuous model of protein conformational space for template-free modeling.

PubMed

Zhao, Feng; Peng, Jian; Debartolo, Joe; Freed, Karl F; Sosnick, Tobin R; Xu, Jinbo

2010-06-01

One of the major challenges with protein template-free modeling is an efficient sampling algorithm that can explore a huge conformation space quickly. The popular fragment assembly method constructs a conformation by stringing together short fragments extracted from the Protein Data Base (PDB). The discrete nature of this method may limit generated conformations to a subspace in which the native fold does not belong. Another worry is that a protein with really new fold may contain some fragments not in the PDB. This article presents a probabilistic model of protein conformational space to overcome the above two limitations. This probabilistic model employs directional statistics to model the distribution of backbone angles and 2(nd)-order Conditional Random Fields (CRFs) to describe sequence-angle relationship. Using this probabilistic model, we can sample protein conformations in a continuous space, as opposed to the widely used fragment assembly and lattice model methods that work in a discrete space. We show that when coupled with a simple energy function, this probabilistic method compares favorably with the fragment assembly method in the blind CASP8 evaluation, especially on alpha or small beta proteins. To our knowledge, this is the first probabilistic method that can search conformations in a continuous space and achieves favorable performance. Our method also generated three-dimensional (3D) models better than template-based methods for a couple of CASP8 hard targets. The method described in this article can also be applied to protein loop modeling, model refinement, and even RNA tertiary structure prediction.

RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures

PubMed Central

2010-01-01

Background Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB) in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization. Description RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics) is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA structures is provided. RNA FRABASE 2.0 is freely available at http://rnafrabase.cs.put.poznan.pl. Conclusions RNA FRABASE 2.0 provides a novel database and powerful search engine which is equipped with new data and functionalities that are unavailable elsewhere. Our intention is that this advanced version of the RNA FRABASE will be of interest to all researchers working in the RNA field. PMID:20459631

RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures.

PubMed

Popenda, Mariusz; Szachniuk, Marta; Blazewicz, Marek; Wasik, Szymon; Burke, Edmund K; Blazewicz, Jacek; Adamiak, Ryszard W

2010-05-06

Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB) in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization. RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics) is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA structures is provided. RNA FRABASE 2.0 is freely available at http://rnafrabase.cs.put.poznan.pl. RNA FRABASE 2.0 provides a novel database and powerful search engine which is equipped with new data and functionalities that are unavailable elsewhere. Our intention is that this advanced version of the RNA FRABASE will be of interest to all researchers working in the RNA field.

Real time three dimensional sensing system

DOEpatents

Gordon, S.J.

1996-12-31

The invention is a three dimensional sensing system which utilizes two flexibly located cameras for receiving and recording visual information with respect to a sensed object illuminated by a series of light planes. Each pixel of each image is converted to a digital word and the words are grouped into stripes, each stripe comprising contiguous pixels. One pixel of each stripe in one image is selected and an epi-polar line of that point is drawn in the other image. The three dimensional coordinate of each selected point is determined by determining the point on said epi-polar line which also lies on a stripe in the second image and which is closest to a known light plane. 7 figs.

Three-dimensional liquid flattened Luneburg lens with ultra-wide viewing angle and frequency band

NASA Astrophysics Data System (ADS)

Wu, Lingling; Tian, Xiaoyong; Yin, Ming; Li, Dichen; Tang, Yiping

2013-08-01

Traditional Luneburg lens is a dielectric spherical antenna. It can focus the incoming collimated electromagnetic waves on its spherical surface, which causes the incompatibility with the planar feeding and receiving devices. Furthermore, the difficulties in the fabrication process also limited its applications. In this paper, a three-dimensional flattened Luneburg lens with a field-of-view angle up to 180° has been realized based on a liquid medium approach and a 3D-printing process. The fabricated three-dimensional lens showed a broadband transmission characteristic from 12.4 GHz to 18 GHz. The performance of the proposed lens was demonstrated by simulation and experimental results.

Three-Dimensional Super-Resolution: Theory, Modeling, and Field Tests Results

NASA Technical Reports Server (NTRS)

Bulyshev, Alexander; Amzajerdian, Farzin; Roback, Vincent E.; Hines, Glenn; Pierrottet, Diego; Reisse, Robert

2014-01-01

Many flash lidar applications continue to demand higher three-dimensional image resolution beyond the current state-of-the-art technology of the detector arrays and their associated readout circuits. Even with the available number of focal plane pixels, the required number of photons for illuminating all the pixels may impose impractical requirements on the laser pulse energy or the receiver aperture size. Therefore, image resolution enhancement by means of a super-resolution algorithm in near real time presents a very attractive solution for a wide range of flash lidar applications. This paper describes a superresolution technique and illustrates its performance and merits for generating three-dimensional image frames at a video rate.

Design of three-dimensional nonimaging concentrators with inhomogeneous media

NASA Astrophysics Data System (ADS)

Minano, J. C.

1986-09-01

A three-dimensional nonimaging concentrator is an optical system that transforms a given four-parametric manifold of rays reaching a surface (entry aperture) into another four-parametric manifold of rays reaching the receiver. A procedure of design of such concentrators is developed. In general, the concentrators use mirrors and inhomogeneous media (i.e., gradient-index media). The concentrator has the maximum concentration allowed by the theorem of conservation of phase-space volume. This is the first known concentrator with such properties. The Welford-Winston edge-ray principle in three-dimensional geometry is proven under several assumptions. The linear compound parabolic concentrator is derived as a particular case of the procedure of design.

Real time three dimensional sensing system

DOEpatents

Gordon, Steven J.

1996-01-01

The invention is a three dimensional sensing system which utilizes two flexibly located cameras for receiving and recording visual information with respect to a sensed object illuminated by a series of light planes. Each pixel of each image is converted to a digital word and the words are grouped into stripes, each stripe comprising contiguous pixels. One pixel of each stripe in one image is selected and an epi-polar line of that point is drawn in the other image. The three dimensional coordinate of each selected point is determined by determining the point on said epi-polar line which also lies on a stripe in the second image and which is closest to a known light plane.

Loop models, modular invariance, and three-dimensional bosonization

NASA Astrophysics Data System (ADS)

Goldman, Hart; Fradkin, Eduardo

2018-05-01

We consider a family of quantum loop models in 2+1 spacetime dimensions with marginally long-ranged and statistical interactions mediated by a U (1 ) gauge field, both purely in 2+1 dimensions and on a surface in a (3+1)-dimensional bulk system. In the absence of fractional spin, these theories have been shown to be self-dual under particle-vortex duality and shifts of the statistical angle of the loops by 2 π , which form a subgroup of the modular group, PSL (2 ,Z ) . We show that careful consideration of fractional spin in these theories completely breaks their statistical periodicity and describe how this occurs, resolving a disagreement with the conformal field theories they appear to approach at criticality. We show explicitly that incorporation of fractional spin leads to loop model dualities which parallel the recent web of (2+1)-dimensional field theory dualities, providing a nontrivial check on its validity.

Studies of Single Biomolecules, DNA Conformational Dynamics, and Protein Binding

DTIC Science & Technology

2008-07-11

Nucleotide Base pairs Hydrogen bonds FIG. 1: Ladder structure of DNA showing the Watson - Crick bonding of the bases A, T, G, and C which are suspended by a...protected against unwanted action of chemicals and proteins. The three-dimensional structure of DNA is the famed Watson - Crick double-helix, the equilibrium...quantitative analysis [88]. [1] A. Kornberg and T. A. Baker, DNA Replication (W. H. Freeman, New York, 1992). [2] J. D. Watson and F. H. C. Crick

Protein conformational disorder and enzyme catalysis.

PubMed

Schulenburg, Cindy; Hilvert, Donald

2013-01-01

Though lacking a well-defined three-dimensional structure, intrinsically unstructured proteins are ubiquitous in nature. These molecules play crucial roles in many cellular processes, especially signaling and regulation. Surprisingly, even enzyme catalysis can tolerate substantial disorder. This observation contravenes conventional wisdom but is relevant to an understanding of how protein dynamics modulates enzyme function. This chapter reviews properties and characteristics of disordered proteins, emphasizing examples of enzymes that lack defined structures, and considers implications of structural disorder for catalytic efficiency and evolution.

The role of structural parameters in DNA cyclization

DOE PAGES

Alexandrov, Ludmil B.; Bishop, Alan R.; Rasmussen, Kim O.; ...

2016-02-04

The intrinsic bendability of DNA plays an important role with relevance for myriad of essential cellular mechanisms. The flexibility of a DNA fragment can be experimentally and computationally examined by its propensity for cyclization, quantified by the Jacobson-Stockmayer J factor. In this paper, we use a well-established coarse-grained three-dimensional model of DNA and seven distinct sets of experimentally and computationally derived conformational parameters of the double helix to evaluate the role of structural parameters in calculating DNA cyclization.

Time-Domain Computation Of Electromagnetic Fields In MMICs

NASA Technical Reports Server (NTRS)

Lansing, Faiza S.; Rascoe, Daniel L.

1995-01-01

Maxwell's equations solved on three-dimensional, conformed orthogonal grids by finite-difference techniques. Method of computing frequency-dependent electrical parameters of monolithic microwave integrated circuit (MMIC) involves time-domain computation of propagation of electromagnetic field in response to excitation by single pulse at input terminal, followed by computation of Fourier transforms to obtain frequency-domain response from time-domain response. Parameters computed include electric and magnetic fields, voltages, currents, impedances, scattering parameters, and effective dielectric constants. Powerful and efficient means for analyzing performance of even complicated MMIC.

Five-Year Outcomes, Cosmesis, and Toxicity With 3-Dimensional Conformal External Beam Radiation Therapy to Deliver Accelerated Partial Breast Irradiation

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

Rodríguez, Núria, E-mail: nrodriguez@parcdesalutmar.cat; Universidad Pompeu Fabra, Barcelona; Sanz, Xavier

2013-12-01

Purpose: To report the interim results from a study comparing the efficacy, toxicity, and cosmesis of breast-conserving treatment with accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy (3D-CRT). Methods and Materials: 102 patients with early-stage breast cancer who underwent breast-conserving surgery were randomized to receive either WBI (n=51) or APBI (n=51). In the WBI arm, 48 Gy was delivered to the whole breast in daily fractions of 2 Gy, with or without additional 10 Gy to the tumor bed. In the APBI arm, patients received 37.5 Gy in 3.75 Gy permore » fraction delivered twice daily. Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Skin elasticity was measured using a dedicated device (Multi-Skin-Test-Center MC-750-B2, CKelectronic-GmbH). Cosmetic results were assessed by the physician and the patients as good/excellent, regular, or poor. Results: The median follow-up time was 5 years. No local recurrences were observed. No significant differences in survival rates were found. APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI (P<.01). Late skin toxicity was no worse than grade 2 in either group, without significant differences between the 2 groups. In the ipsilateral breast, the areas that received the highest doses (ie, the boost or quadrant) showed the greatest loss of elasticity. WBI resulted in a greater loss of elasticity in the high-dose area compared with APBI (P<.05). Physician assessment showed that >75% of patients in the APBI arm had excellent or good cosmesis, and these outcomes appear to be stable over time. The percentage of patients with excellent/good cosmetic results was similar in both groups. Conclusions: APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI.« less

Quantum integrable systems from conformal blocks

NASA Astrophysics Data System (ADS)

Chen, Heng-Yu; Qualls, Joshua D.

2017-05-01

In this note, we extend the striking connections between quantum integrable systems and conformal blocks recently found in [M. Isachenkov and V. Schomerus, Phys. Rev. Lett. 117, 071602 (2016), 10.1103/PhysRevLett.117.071602] in several directions. First, we explicitly demonstrate that the action of the quartic conformal Casimir operator on general d-dimensional scalar conformal blocks can be expressed in terms of certain combinations of commuting integrals of motions of the two particle hyperbolic BC2 Calogero-Sutherland system. The permutation and reflection properties of the underlying Dunkl operators play crucial roles in establishing such a connection. Next, we show that the scalar superconformal blocks in superconformal field theories (SCFTs) with four and eight supercharges and suitable chirality constraints can also be identified with the eigenfunctions of the same Calogero-Sutherland system; this demonstrates the universality of such a connection. Finally, we observe that the so-called "seed" conformal blocks for constructing four point functions for operators with arbitrary space-time spins in four-dimensional CFTs can also be linearly expanded in terms of Calogero-Sutherland eigenfunctions.

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

PubMed

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

2015-04-17

Defining the conformational states of cytochrome P450 active sites is critical for the design of agents that minimize drug-drug interactions, the development of isoform-specific P450 inhibitors, and the engineering of novel oxidative catalysts. We used two-dimensional (1)H,(15)N HSQC chemical shift perturbation mapping of (15)N-labeled Phe residues and x-ray crystallography to examine the ligand-dependent conformational dynamics of CYP119. Active site Phe residues were most affected by the binding of azole inhibitors and fatty acid substrates, in agreement with active site localization of the conformational changes. This was supported by crystallography, which revealed movement of the F-G loop with various azoles. Nevertheless, the NMR chemical shift perturbations caused by azoles and substrates were distinguishable. The absence of significant chemical shift perturbations with several azoles revealed binding of ligands to an open conformation similar to that of the ligand-free state. In contrast, 4-phenylimidazole caused pronounced NMR changes involving Phe-87, Phe-144, and Phe-153 that support the closed conformation found in the crystal structure. The same closed conformation is observed by NMR and crystallography with a para-fluoro substituent on the 4-phenylimidazole, but a para-chloro or bromo substituent engendered a second closed conformation. An open conformation is thus favored in solution with many azole ligands, but para-substituted phenylimidazoles give rise to two closed conformations that depend on the size of the para-substituent. The results suggest that ligands selectively stabilize discrete cytochrome P450 conformational states. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Analysis of Cytochrome P450 CYP119 Ligand-dependent Conformational Dynamics by Two-dimensional NMR and X-ray Crystallography

DOE PAGES

Basudhar, Debashree; Madrona, Yarrow; Kandel, Sylvie; ...

2015-02-10

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

Analysis of Cytochrome P450 CYP119 Ligand-dependent Conformational Dynamics by Two-dimensional NMR and X-ray Crystallography

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

Basudhar, Debashree; Madrona, Yarrow; Kandel, Sylvie

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

Higher spin realization of the DS/CFT correspondence

NASA Astrophysics Data System (ADS)

Anninos, Dionysios; Hartman, Thomas; Strominger, Andrew

2017-01-01

We conjecture that Vasiliev’s theory of higher spin gravity in four-dimensional de Sitter space (dS4) is holographically dual to a three-dimensional conformal field theory (CFT3) living on the spacelike boundary of dS4 at future timelike infinity. The CFT3 is the Euclidean Sp(N) vector model with anticommuting scalars. The free CFT3 flows under a double-trace deformation to an interacting CFT3 in the IR. We argue that both CFTs are dual to Vasiliev dS4 gravity but with different future boundary conditions on the bulk scalar field. Our analysis rests heavily on analytic continuations of bulk and boundary correlators in the proposed duality relating the O(N) model with Vasiliev gravity in AdS4.

A comparison of design variables for control theory based airfoil optimization

NASA Technical Reports Server (NTRS)

Reuther, James; Jameson, Antony

1995-01-01

This paper describes the implementation of optimization techniques based on control theory for airfoil design. In our previous work in the area it was shown that control theory could be employed to devise effective optimization procedures for two-dimensional profiles by using either the potential flow or the Euler equations with either a conformal mapping or a general coordinate system. We have also explored three-dimensional extensions of these formulations recently. The goal of our present work is to demonstrate the versatility of the control theory approach by designing airfoils using both Hicks-Henne functions and B-spline control points as design variables. The research also demonstrates that the parameterization of the design space is an open question in aerodynamic design.

Prediction of subsonic vortex shedding from forebodies with chines

NASA Technical Reports Server (NTRS)

Mendenhall, Michael R.; Lesieutre, Daniel J.

1990-01-01

An engineering prediction method and associated computer code VTXCHN to predict nose vortex shedding from circular and noncircular forebodies with sharp chine edges in subsonic flow at angles of attack and roll are presented. Axisymmetric bodies are represented by point sources and doublets, and noncircular cross sections are transformed to a circle by either analytical or numerical conformal transformations. The lee side vortex wake is modeled by discrete vortices in crossflow planes along the body; thus the three-dimensional steady flow problem is reduced to a two-dimensional, unsteady, separated flow problem for solution. Comparison of measured and predicted surface pressure distributions, flow field surveys, and aerodynamic characteristics are presented for noncircular bodies alone and forebodies with sharp chines.

Three-Dimensional Steerable Magnetic Field (3DSMF)Sensor System for Classification of Buried Metal Targets

DTIC Science & Technology

2006-07-01

technical approach overview .............................................................................. 4 Figure 2 Magnetic field lines around a loop ...11 Figure 10 HMF (Bx) and loop (Bz) antenna comparison .............................................................. 12...Figure 26 Top view of one proposed receiver loop arrangement. ................................................ 25 Figure 27 Receiver response modeling

Three-Dimensional Steerable Magnetic Field (3DSMF) Sensor System for Classification of Buried Metal Targets

DTIC Science & Technology

2006-07-01

technical approach overview .............................................................................. 4 Figure 2 Magnetic field lines around a loop ...11 Figure 10 HMF (Bx) and loop (Bz) antenna comparison .............................................................. 12 Figure...26 Top view of one proposed receiver loop arrangement. ................................................ 25 Figure 27 Receiver response modeling

75 FR 21530 - Airworthiness Directives; Bombardier, Inc. Model DHC-8-200 and DHC-8-300 Series Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... fuel system test, it was found that all three flapper valves located in each collector tank did not conform to the design requirements, due to the fact that a valve spring was installed on the flapper hinge... ADs. We will post all comments we receive, without change, to http://www.regulations.gov , including...

Pt-Al2O3 dual layer atomic layer deposition coating in high aspect ratio nanopores.

PubMed

Pardon, Gaspard; Gatty, Hithesh K; Stemme, Göran; van der Wijngaart, Wouter; Roxhed, Niclas

2013-01-11

Functional nanoporous materials are promising for a number of applications ranging from selective biofiltration to fuel cell electrodes. This work reports the functionalization of nanoporous membranes using atomic layer deposition (ALD). ALD is used to conformally deposit platinum (Pt) and aluminum oxide (Al(2)O(3)) on Pt in nanopores to form a metal-insulator stack inside the nanopore. Deposition of these materials inside nanopores allows the addition of extra functionalities to nanoporous materials such as anodic aluminum oxide (AAO) membranes. Conformal deposition of Pt on such materials enables increased performances for electrochemical sensing applications or fuel cell electrodes. An additional conformal Al(2)O(3) layer on such a Pt film forms a metal-insulator-electrolyte system, enabling field effect control of the nanofluidic properties of the membrane. This opens novel possibilities in electrically controlled biofiltration. In this work, the deposition of these two materials on AAO membranes is investigated theoretically and experimentally. Successful process parameters are proposed for a reliable and cost-effective conformal deposition on high aspect ratio three-dimensional nanostructures. A device consisting of a silicon chip supporting an AAO membrane of 6 mm diameter and 1.3 μm thickness with 80 nm diameter pores is fabricated. The pore diameter is reduced to 40 nm by a conformal deposition of 11 nm Pt and 9 nm Al(2)O(3) using ALD.

Pt-Al2O3 dual layer atomic layer deposition coating in high aspect ratio nanopores

NASA Astrophysics Data System (ADS)

Pardon, Gaspard; Gatty, Hithesh K.; Stemme, Göran; van der Wijngaart, Wouter; Roxhed, Niclas

2013-01-01

Functional nanoporous materials are promising for a number of applications ranging from selective biofiltration to fuel cell electrodes. This work reports the functionalization of nanoporous membranes using atomic layer deposition (ALD). ALD is used to conformally deposit platinum (Pt) and aluminum oxide (Al2O3) on Pt in nanopores to form a metal-insulator stack inside the nanopore. Deposition of these materials inside nanopores allows the addition of extra functionalities to nanoporous materials such as anodic aluminum oxide (AAO) membranes. Conformal deposition of Pt on such materials enables increased performances for electrochemical sensing applications or fuel cell electrodes. An additional conformal Al2O3 layer on such a Pt film forms a metal-insulator-electrolyte system, enabling field effect control of the nanofluidic properties of the membrane. This opens novel possibilities in electrically controlled biofiltration. In this work, the deposition of these two materials on AAO membranes is investigated theoretically and experimentally. Successful process parameters are proposed for a reliable and cost-effective conformal deposition on high aspect ratio three-dimensional nanostructures. A device consisting of a silicon chip supporting an AAO membrane of 6 mm diameter and 1.3 μm thickness with 80 nm diameter pores is fabricated. The pore diameter is reduced to 40 nm by a conformal deposition of 11 nm Pt and 9 nm Al2O3 using ALD.

Sound Source Localization Using Non-Conformal Surface Sound Field Transformation Based on Spherical Harmonic Wave Decomposition

PubMed Central

Zhang, Lanyue; Ding, Dandan; Yang, Desen; Wang, Jia; Shi, Jie

2017-01-01

Spherical microphone arrays have been paid increasing attention for their ability to locate a sound source with arbitrary incident angle in three-dimensional space. Low-frequency sound sources are usually located by using spherical near-field acoustic holography. The reconstruction surface and holography surface are conformal surfaces in the conventional sound field transformation based on generalized Fourier transform. When the sound source is on the cylindrical surface, it is difficult to locate by using spherical surface conformal transform. The non-conformal sound field transformation by making a transfer matrix based on spherical harmonic wave decomposition is proposed in this paper, which can achieve the transformation of a spherical surface into a cylindrical surface by using spherical array data. The theoretical expressions of the proposed method are deduced, and the performance of the method is simulated. Moreover, the experiment of sound source localization by using a spherical array with randomly and uniformly distributed elements is carried out. Results show that the non-conformal surface sound field transformation from a spherical surface to a cylindrical surface is realized by using the proposed method. The localization deviation is around 0.01 m, and the resolution is around 0.3 m. The application of the spherical array is extended, and the localization ability of the spherical array is improved. PMID:28489065

Conformal and projective symmetries in Newtonian cosmology

NASA Astrophysics Data System (ADS)

Duval, C.; Gibbons, G. W.; Horváthy, P. A.

2017-02-01

Definitions of non-relativistic conformal transformations are considered both in the Newton-Cartan and in the Kaluza-Klein-type Eisenhart/Bargmann geometrical frameworks. The symmetry groups that come into play are exemplified by the cosmological, and also the Newton-Hooke solutions of Newton's gravitational field equations. It is shown, in particular, that the maximal symmetry group of the standard cosmological model is isomorphic to the 13-dimensional conformal-Newton-Cartan group whose conformal-Bargmann extension is explicitly worked out. Attention is drawn to the appearance of independent space and time dilations, in contrast with the Schrödinger group or the Conformal Galilei Algebra.

Observationally constrained modeling of sound in curved ocean internal waves: examination of deep ducting and surface ducting at short range.

PubMed

Duda, Timothy F; Lin, Ying-Tsong; Reeder, D Benjamin

2011-09-01

A study of 400 Hz sound focusing and ducting effects in a packet of curved nonlinear internal waves in shallow water is presented. Sound propagation roughly along the crests of the waves is simulated with a three-dimensional parabolic equation computational code, and the results are compared to measured propagation along fixed 3 and 6 km source/receiver paths. The measurements were made on the shelf of the South China Sea northeast of Tung-Sha Island. Construction of the time-varying three-dimensional sound-speed fields used in the modeling simulations was guided by environmental data collected concurrently with the acoustic data. Computed three-dimensional propagation results compare well with field observations. The simulations allow identification of time-dependent sound forward scattering and ducting processes within the curved internal gravity waves. Strong acoustic intensity enhancement was observed during passage of high-amplitude nonlinear waves over the source/receiver paths, and is replicated in the model. The waves were typical of the region (35 m vertical displacement). Two types of ducting are found in the model, which occur asynchronously. One type is three-dimensional modal trapping in deep ducts within the wave crests (shallow thermocline zones). The second type is surface ducting within the wave troughs (deep thermocline zones). © 2011 Acoustical Society of America

[A wireless power transmission system for capsule endoscope].

PubMed

Xin, Wenhui; Yan, Guozheng; Wang, Wenxing

2010-06-01

In order to deliver power to the capsule endoscope, whose position and orientation are always changing when traveling along the alimentary tract, a wireless power transmission system based on electromagnetic coupling was proposed. The system is composed of Helmholtz transmitting coil and three-dimensional receiving coil. Helmholtz coil outside the body generates a uniform magnetic field covering the whole alimentary tract; three-dimensional coil inside retrieves stable power regardless of its position and orientation. The transmitter and receiver were designed and implemented, and the experiments validated the feasibility of the system. The results show that at least 320 mW of usable power can be transmitted to capsule endoscope when its position and orientation are changing at random and the transmitting power is 25W.

Functional analysis of propeptide as an intramolecular chaperone for in vivo folding of subtilisin nattokinase.

PubMed

Jia, Yan; Liu, Hui; Bao, Wei; Weng, Meizhi; Chen, Wei; Cai, Yongjun; Zheng, Zhongliang; Zou, Guolin

2010-12-01

Here, we show that during in vivo folding of the precursor, the propeptide of subtilisin nattokinase functions as an intramolecular chaperone (IMC) that organises the in vivo folding of the subtilisin domain. Two residues belonging to β-strands formed by conserved regions of the IMC are crucial for the folding of the subtilisin domain through direct interactions. An identical protease can fold into different conformations in vivo due to the action of a mutated IMC, resulting in different kinetic parameters. Some interfacial changes involving conserved regions, even those induced by the subtilisin domain, blocked subtilisin folding and altered its conformation. Insight into the interaction between the subtilisin and IMC domains is provided by a three-dimensional structural model. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Tris[(6S)-6-hy­droxy-4-epi-shikimic acid] monohydrate: an enanti­omerically pure hy­droxy­lated shikimic acid derived from methyl shikimate

PubMed Central

Griesbeck, Axel G.; Miara, Claus; Neudörfl, Jörg-M.

2012-01-01

The title compound, 3C7H10O6·H2O, is the enanti­omerically pure product of a multi-step synthesis from the enanti­omerically pure natural shikimic acid. The asymmetric unit contains three mol­ecules of the acid and one mol­ecule of water. The cyclo­hexene rings of the acids have half-chair conformations. The carboxyl­ate, the four hydroxide groups and the additional water mol­ecule form a complex three-dimensional hydrogen-bonding network. PMID:23284468

Regulation of Response Regulator Autophosphorylation through Interdomain Contacts*♦

PubMed Central

Barbieri, Christopher M.; Mack, Timothy R.; Robinson, Victoria L.; Miller, Matthew T.; Stock, Ann M.

2010-01-01

DNA-binding response regulators (RRs) of the OmpR/PhoB subfamily alternate between inactive and active conformational states, with the latter having enhanced DNA-binding affinity. Phosphorylation of an aspartate residue in the receiver domain, usually via phosphotransfer from a cognate histidine kinase, stabilizes the active conformation. Many of the available structures of inactive OmpR/PhoB family proteins exhibit extensive interfaces between the N-terminal receiver and C-terminal DNA-binding domains. These interfaces invariably involve the α4-β5-α5 face of the receiver domain, the locus of the largest differences between inactive and active conformations and the surface that mediates dimerization of receiver domains in the active state. Structures of receiver domain dimers of DrrB, DrrD, and MtrA have been determined, and phosphorylation kinetics were analyzed. Analysis of phosphotransfer from small molecule phosphodonors has revealed large differences in autophosphorylation rates among OmpR/PhoB RRs. RRs with substantial domain interfaces exhibit slow rates of phosphorylation. Rates are greatly increased in isolated receiver domain constructs. Such differences are not observed between autophosphorylation rates of full-length and isolated receiver domains of a RR that lacks interdomain interfaces, and they are not observed in histidine kinase-mediated phosphotransfer. These findings suggest that domain interfaces restrict receiver domain conformational dynamics, stabilizing an inactive conformation that is catalytically incompetent for phosphotransfer from small molecule phosphodonors. Inhibition of phosphotransfer by domain interfaces provides an explanation for the observation that some RRs cannot be phosphorylated by small molecule phosphodonors in vitro and provides a potential mechanism for insulating some RRs from small molecule-mediated phosphorylation in vivo. PMID:20702407

Predicting pneumonitis risk: a dosimetric alternative to mean lung dose.

PubMed

Tucker, Susan L; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K; Liao, Zhongxing

2013-02-01

To determine whether the association between mean lung dose (MLD) and risk of severe (grade ≥3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. The incidence of grade ≥3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. When predicting risk of grade ≥3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ("a lot to a little") are worse than low doses to large volumes ("a little to a lot"). Copyright © 2013 Elsevier Inc. All rights reserved.

The Minkowski metric in non-inertial observer radar coordinates

NASA Astrophysics Data System (ADS)

Minguzzi, E.

2005-12-01

We give a closed expression for the Minkowski (1+1)-dimensional metric in the radar coordinates of an arbitrary non-inertial observer O in terms of O's proper acceleration. Knowledge of the metric allows the non-inertial observer to perform experiments in spacetime without making reference to inertial frames. To clarify the relation between inertial and non-inertial observers the coordinate transformation between radar and inertial coordinates also is given. We show that every conformally flat coordinate system can be regarded as the radar coordinate system of a suitable observer for a suitable parametrization of the observer worldline. Therefore, the coordinate transformation between arbitrarily moving observers is a conformal transformation and conformally invariant (1+1)-dimensional theories lead to the same physics for all observers, independently of their relative motion.