Biomedical subjects

Nikolaos V Sahinidis

Publications and source records attributed to Nikolaos V Sahinidis.

4 recordsLinked to original sources

PubMed2006

In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma.

Drug-releasing implants delivering chemotherapeutic and radio-sensitizing agents are beginning to play a major role in the post-surgical eradication of residual glioma in the brain. Benefits from early arresting of tumor growth and tumor recovery dynamics stress the impact of drug release profiles of the implants on the efficacy of the treatment. This paper examines responses of BALB/c nude mice, bearing C6 glioma tumors subcutaneously, to treatments by PLGA microspheres, microparticles and discs-delivering Paclitaxel and Etanidazole. The experimental results are used to correlate the efficacy of treatment to in vitro release profiles from the various formulations. Our study demonstrates that radio-sensitizing effects during irradiation could be achieved by double burst profiles from Etanidazole-loaded discs, when compared to controls 17 days after implantation despite the short half-life of Etanidazole (1.4h) in vivo. These results also showed inhibited tumor growth on tumor volumes of 59%, 65% and 70% over the blank placebo groups after 21 days of tumor growth for spray-dried microspheres, electrohydrodynamic atomization microparticles and spray-dried discs, respectively.

Animals↗

PubMed2005

Residue-rotamer-reduction algorithm for the protein side-chain conformation problem.

MOTIVATION: The protein side-chain conformation problem is a central problem in proteomics with wide applications in protein structure prediction and design. Computational complexity results show that the problem is hard to solve. Yet, instances from realistic applications are large and demand fast and reliable algorithms. RESULTS: We propose a new global optimization algorithm, which for the first time integrates residue reduction and rotamer reduction techniques previously developed for the protein side-chain conformation problem. We show that the proposed approach simplifies dramatically the topology of the underlining residue graph. Computations show that our algorithm solves problems using only 1-10% of the time required by the mixed-integer linear programming approach available in the literature. In addition, on a set of hard side-chain conformation problems, our algorithm runs 2-78 times faster than SCWRL 3.0, which is widely used for solving these problems. AVAILABILITY: The implementation is available as an online server at http://eudoxus.scs.uiuc.edu/r3.html

Algorithms↗

PubMed2005

Polynomial-time algorithms for the integer minimal principle for centrosymmetric structures.

The minimal principle for structure determination from single-crystal X-ray diffraction measurements has recently been formulated as an integer linear optimization model for the case of centrosymmetric structures. Solution of this model via established combinatorial branch-and-bound algorithms provides the true global minimum of the minimal principle while operating exclusively in reciprocal space. However, integer programming techniques may require an exponential number of iterations to exhaust the search space. In this paper, a new approach is developed to solve the integer minimal principle to global optimality without requiring the solution of an optimization problem. Instead, properties of the solution of the optimization problem, as observed in a large number of computational experiments, are exploited in order to reduce the optimization formulation to a system of linear equations in the number field of two elements (F(2)). Two specialized Gaussian elimination algorithms are then developed to solve this system of equations in polynomial time in the number of atoms. Computational results on a collection of 38 structures demonstrate that the proposed approach provides very fast and accurate solutions to the phase problem for centrosymmetric structures. This approach also provided much better crystallographic R values than SHELXS for all 38 structures tested.

Algorithms↗

PubMed2003

An integer programming approach to the phase problem for centrosymmetric structures.

The problem addressed in this paper is the determination of three-dimensional structures of centrosymmetric crystals from X-ray diffraction measurements. The 'minimal principle' that a certain quantity is minimized only by the crystal structure is employed to solve the phase problem. The mathematical formulation of the minimal principle is a nonconvex nonlinear optimization problem. To date, local optimization techniques and advanced computer architectures have been used to solve this problem, which may have a very large number of local optima. In this paper, the minimal principle model is reformulated for the case of centrosymmetric structures into an integer programming problem in terms of the missing phases. This formulation is solvable by well established combinatorial optimization techniques that are guaranteed to provide the global optimum in a finite number of steps without explicit enumeration of all possible combinations of phases. Computational experience with the proposed method on a number of structures of moderate complexity is provided and demonstrates that the approach yields a fast and reliable method that resolves the crystallographic phase problem for the case of centrosymmetric structures.

Journal Article↗