Optimized Treatment Schedules for Chronic Myeloid Leukemia

Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substan- tial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies. However, the design of such combination therapies (timing, sequence, etc.) remains an open challenge. In this work we mathematically model the dynamics of CML response to combination therapy and analyze the impact of combination treatment schedules on treatment efficacy in patients with preexisting resistance. We then propose an optimization problem to find the best schedule of multiple therapies based on the evolution of CML according to our ordinary differential equation model. This resulting optimiza- tion problem is nontrivial due to the presence of ordinary different equation constraints and integer variables. Our model also incorporates realistic drug toxicity constraints by tracking the dynamics of patient neutrophil counts in response to therapy. Using realis- tic parameter estimates, we determine optimal combination strategies that maximize time until treatment failure.Comment: 26 pages, 7 figure

El perfil de las revistas españolas de comunicación (2007-2008)

La evolución de los parámetros de publicación científi ca y de las exigencias de la carrera académica en España ha provocado cambios en las revistas científi cas y, entre ellas, las de comunicación. Este artículo caracteriza las revistas nucleares españolas en el ámbito de la comunicación a través de variables como el volumen de artículos publicados, el idioma empleado, la procedencia y las redes de colaboración de sus autores o los patrones de citación en el período 2007-2008. Mediante técnicas bibliométricas y el análisis de redes sociales se obtiene un perfi l que muestra las similitudes y las diferencias entre las diferentes revistas y el perfi l del conjunto del sistema.The evolution of parameters for scholarly publications and of academic requirements in Spain has resulted in changes to scholarly journals, among others, those in the fi eld of communication sciences. This article characterizes the core Spanish communication journals according to variables such as the number of published articles, language, author institution and collaboration networks, and citation patterns during 2007-2008. By applying bibliometric techniques and social network analysis, a profile showing similarities and differences among the journals is obtained, as well as a profile of the overall system

Giant, Voltage-Actuated Deformation of a Dielectric Elastomer under Dead Load

Far greater voltage-actuated deformation is achievable for a dielectric elastomer under equal-biaxial dead load than under rigid constraint usually employed. Areal strains of 488% are demonstrated. The dead load suppresses electric breakdown, enabling the elastomer to survive the snap-through electromechanical instability. The breakdown voltage is found to increase with the voltage ramp rate. A nonlinear model for viscoelastic dielectric elastomers is developed and shown to be consistent with the experimental observations.Engineering and Applied Science

Evaluation of the diffusion equation for modeling reverberant electromagnetic fields

Determination of the distribution of electromagnetic energy inside electrically large enclosed spaces is important in many electromagnetic compatibility applications, such as certification of aircraft and equipment shielding enclosures. The field inside such enclosed environments contains a dominant diffuse component due to multiple randomizing reflections from the enclosing surfaces. The power balance technique has been widely applied to the analysis of such problems; however, it is unable to account for the inhomogeneities in the field that arise when the absorption in the walls and contents of the enclosure is significant. In this paper we show how a diffusion equation approach can be applied to modeling diffuse electromagnetic fields and evaluate its potential for use in electromagnetic compatibility applications. Two canonical examples were investigated: A loaded cavity and two cavities coupled by a large aperture. The predictions of the diffusion model were compared to measurement data and found to be in good agreement. The diffusion model has a very low computational cost compared to other applicable techniques, such as full-wave simulation and ray-tracing, offering the potential for a radical increase in the efficiency of the solution high frequency electromagnetic shielding problems with complex topologies

Control of construction costs during construction

The construction of a major project requires a vast amount of time, money, material and human resources. Proper coordination of these elements into an array of activities is crutial to the success of the project if it is to be built on time and within budget. As technology advances, the complexity of the project increases the resources to build them remain finite, and therefore, the project manager must seek methods to improve control on the construction project. This thesis provides an overall view of the relatively new and rapidly expanding field of cost engineering. Cost engineering may be defined as that field of engineering practice where engineering judgement and experience are utilized in the application of science principles and techniques to the areas of cost estimation and cost control. Cost estimation and cost control will be the main subject of this thesis. Although this area has tremendous impact on the economics of private industries and the goverment, cost estimating and cost control has usually underestimated. Virtually all decisions to construct a facility is based on economics, inturn, the economic study is based on the accuracy of an estimate. Once management has committed itself to the project, cost control protects its decision and holds expenditures within budget by constant monitoring and appraisal of cost performance of those responsible for executing the project. The text will provide the reader with the basic understanding of the nature of construction costs, the types and importance of estimates, budgeting procedures and implementation of a cost control system

Activity evaluation of cocoa pod borer sex pheromone in cacao fields

The previously identified female sex pheromone of cocoa pod borer, Conopomorpha cramerella, was re-evaluated for its attractive activity in different field conditions. It was found that lures containing 100-μg of synthetic sex pheromone blend, (E,Z,Z)- and (E,E,Z)-4,6,10-hexadecatrienyl acetates, and the corresponding alcohols in a ratio of 40:60:4:6 in a polyethylene vial attracted male C. cramerella moths in Sabah and peninsular Malaysia and in Sumatra and Sulawesi, Indonesia, suggesting that the same pheromone strain existed in a wide stretch of the Indo-Malayan archipelago. Of the three kinds of trap designs tested, the Delta traps were more effective than Pherocon V scale traps. Male captures were not significantly different among traps baited with 100-, 300-, or 1,000-μg doses of sex pheromone. A release rate study of pheromone formulation conducted in the laboratory showed that volatile active ingredients were desorbed from polyethylene vials following first-order kinetics, which indicates a satisfactory "half-life time" of a 100-μg loading is ≈6 wk under laboratory conditions. A satisfactory attractiveness of the lure with a 100-μg loading was ≈1-2 mo in the fields

Tako-tsubo cardiomyopathy precipitated by pheochromocytoma crisis

We report the case of a 69 year-old Chinese lady with pheochromocytoma who developed chest pain and acute ST-segment elevation in the anterior leads on electrocardiography. She was given intravenous phenoxybenzamine for alpha-blockade before undergoing urgent coronary angiography. This revealed minor coronary artery disease. Left ventriculogram demonstrated akinesis in the apex with hypercontraction of the basal segments. The Tako-tsubo cardiomyopathy eventually resolved with surgical removal of the pheochromocytoma. This case highlights the challenging management of suspected acute myocardial infarction in pheochromocytoma crisis and also reinforces the notion that Tako-tsubo cardiomyopathy is likely precipitated by catecholamine excess. (Cardiol J 2011; 18, 5: 564–567

Antimicrobial functionalized genetically engineered spider silk

Genetically engineered fusion proteins offer potential as multifunctional biomaterials for medical use. Fusion or chimeric proteins can be formed using recombinant DNA technology by combining nucleotide sequences encoding different peptides or proteins that are otherwise not found together in nature. In the present study, three new fusion proteins were designed, cloned and expressed and assessed for function, by combining the consensus sequence of dragline spider silk with three different antimicrobial peptides. The human antimicrobial peptides human neutrophil defensin 2 (HNP-2), human neutrophil defensins 4 (HNP-4) and hepcidin were fused to spider silk through bioengineering. The spider silk domain maintained its self-assembly features, a key aspect of these new polymeric protein biomaterials, allowing the formation of b-sheets to lock in structures via physical interactions without the need for chemical crosslinking. These new functional silk proteins were assessed for antimicrobial activity against Gram e Escherichia coli and Gram þ Staphylococcus aureus and microbicidal activity was demonstrated. Dynamic light scattering was used to assess protein aggregation to clarify the antimicrobial patterns observed. Attenuated-total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and circular dichroism (CD) were used to assess the secondary structure of the new recombinant proteins. In vitro cell studies with a human osteosarcoma cell line (SaOs-2) demonstrated the compatibility of these new proteins with mammalian cells.Fundação para a Ciência e a Tecnologia (FCT) - Bolsa de doutoramento (SFRH/BD/28603/2006); Chimera project (PTDC/EBB-EBI/109093/2008); NIH and Tissue Engineering Resource Center EB003210, P41 EB002520, DE017207