642 research outputs found

    Monte Carlo Procedure for Protein Design

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    A new method for sequence optimization in protein models is presented. The approach, which has inherited its basic philosophy from recent work by Deutsch and Kurosky [Phys. Rev. Lett. 76, 323 (1996)] by maximizing conditional probabilities rather than minimizing energy functions, is based upon a novel and very efficient multisequence Monte Carlo scheme. By construction, the method ensures that the designed sequences represent good folders thermodynamically. A bootstrap procedure for the sequence space search is devised making very large chains feasible. The algorithm is successfully explored on the two-dimensional HP model with chain lengths N=16, 18 and 32.Comment: 7 pages LaTeX, 4 Postscript figures; minor change

    Low-dose intra-arterial contrast-enhanced MR aortography in patients based on a theoretically derived injection protocol

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    Multiple intra-arterial contrast agent injections are necessary during MR-guided endovascular interventions. In respect to the approved limits of maximum daily gadolinium dose, a low-dose injection protocol is mandatory. The objective of this study was to derive and apply a low-dose injection protocol for intra-arterial 3D contrast-enhanced MR aortography in patients. Injection rate (Qinj), concentration of injected gadolinium [Gd]inj and aortal blood flow rate (Qblood) were included for the theoretical evaluation of signal intensity (SI) of the arterial lumen. SI simulations were carried out at Qinj=2 versus 4ml/s in the [Gd]inj range between 0-500mM. Qinj and [Gd]inj with SI above the 75% threshold of the maximal SI were regarded as optimal injection parameters. [Gd]inj=50mM and Qinj=4ml/s were considered as optimal and were administered in five patients for 3D MR aortography. All images revealed clear delineation of the abdominal aorta and its major branches. Mean±SD of contrast-to-noise ratios of the abdominal aorta, common iliac and renal artery were 70.2±15.2, 58.6±12.3 and 67.4±12.3. Approximately seven intra-aortal injections would be permissible in patients during MR-guided interventions without exceeding the maximal dose of gadoliniu

    Predicting the Next Best View for 3D Mesh Refinement

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    3D reconstruction is a core task in many applications such as robot navigation or sites inspections. Finding the best poses to capture part of the scene is one of the most challenging topic that goes under the name of Next Best View. Recently, many volumetric methods have been proposed; they choose the Next Best View by reasoning over a 3D voxelized space and by finding which pose minimizes the uncertainty decoded into the voxels. Such methods are effective, but they do not scale well since the underlaying representation requires a huge amount of memory. In this paper we propose a novel mesh-based approach which focuses on the worst reconstructed region of the environment mesh. We define a photo-consistent index to evaluate the 3D mesh accuracy, and an energy function over the worst regions of the mesh which takes into account the mutual parallax with respect to the previous cameras, the angle of incidence of the viewing ray to the surface and the visibility of the region. We test our approach over a well known dataset and achieve state-of-the-art results.Comment: 13 pages, 5 figures, to be published in IAS-1

    Identification of Amino Acid Sequences with Good Folding Properties in an Off-Lattice Model

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    Folding properties of a two-dimensional toy protein model containing only two amino-acid types, hydrophobic and hydrophilic, respectively, are analyzed. An efficient Monte Carlo procedure is employed to ensure that the ground states are found. The thermodynamic properties are found to be strongly sequence dependent in contrast to the kinetic ones. Hence, criteria for good folders are defined entirely in terms of thermodynamic fluctuations. With these criteria sequence patterns that fold well are isolated. For 300 chains with 20 randomly chosen binary residues approximately 10% meet these criteria. Also, an analysis is performed by means of statistical and artificial neural network methods from which it is concluded that the folding properties can be predicted to a certain degree given the binary numbers characterizing the sequences.Comment: 15 pages, 8 Postscript figures. Minor change

    Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial

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    Background: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. Patients and methods: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m2 day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m2 d1) and capecitabine (650-800 mg/m2 b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. Results: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m2 d1, d8; oxaliplatin 130 mg/m2 d1 and capecitabine 650 mg/m2 b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. Conclusion: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigation
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