The effects of time valuation in cancer optimal therapies: a study of chronic myeloid leukemia

Background The mathematical design of optimal therapies to fight cancer is an important research field in today’s Biomathematics and Biomedicine given its relevance to formulate patient-specific treatments. Until now, however, cancer optimal therapies have considered that malignancy exclusively depends on the drug concentration and the number of cancer cells, ignoring that the faster the cancer grows the worse the cancer is, and that early drug doses are more prejudicial. Here, we analyze how optimal therapies are affected when the time evolution of treated cancer is envisaged as an additional element determining malignancy, analyzing in detail the implications for imatinib-treated Chronic Myeloid Leukemia. Methods Taking as reference a mathematical model describing Chronic Myeloid Leukemia dynamics, we design an optimal therapy problem by modifying the usual malignancy objective function, unaware of any temporal dimension of cancer malignance. In particular, we introduce a time valuation factor capturing the increase of malignancy associated to the quick development of the disease and the persistent negative effects of initial drug doses. After assigning values to the parameters involved, we solve and simulate the model with and without the new time valuation factor, comparing the results for the drug doses and the evolution of the disease. Results Our computational simulations unequivocally show that the consideration of a time valuation factor capturing the higher malignancy associated with early growth of cancer and drug administration allows more efficient therapies to be designed. More specifically, when this time valuation factor is incorporated into the objective function, the optimal drug doses are lower, and do not involve medically relevant increases in the number of cancer cells or in the disease duration. Conclusions In the light of our simulations and as biomedical evidence strongly suggests, the existence of a time valuation factor affecting malignancy in treated cancer cannot be ignored when designing cancer optimal therapies. Indeed, the consideration of a time valuation factor modulating malignancy results in significant gains of efficiency in the optimal therapy with relevant implications from the biomedical perspective, specially when designing patient-specific treatments.This work was supported by projects MTM2014-56022-C2-2-P and MTM2017-85476-C2-1-P of the Spanish Office of Innovation and Competitiveness and European FEDER Funds, and by projects of the Castile and León Autonomous Government: VA041P17 (with European FEDER Funds), VA138G18 and VA148G18

Reactive Palladium Carbenes: Migratory Insertion and Other Carbene-Hydrocarbyl Coupling Reactions on Well-Defined Systems

Producción CientíficaPalladium complexes with carbene ligands are among the best known and more extensively used catalysts. Those carbenes are usually NHC or N,N-disubstituted derivatives and their use relies on the robust nature of the carbene ligands and their role as auxiliary ligands that modify the metal's elec- tronic and steric features. In contrast, there are other types of carbenes that, when coordinated to palladium, lead to transfor- mations in which the carbene fragment is involved. In the last decade, palladium-catalyzed reactions have been extended to the use of carbene precursors that can be functionalized with the formation of several C–C bonds in one reaction step. Plausi- ble mechanisms have been proposed where a carbene–hydro- carbyl coupling occurs in the palladium coordination sphere. This microreview aims to collect and discuss the examples of organometallic reactions in well-characterized palladium com- plexes where the carbene is one of the fragments involved in C–C bond formation. These examples are key in understanding and supporting the mechanisms proposed for the Pd-catalyzed of C–C coupling reactions of carbenes.MINECO (SGPI, grant CTQ2016-80913-P)Junta de Castilla y León (grants VA062G18 and VA051P17

Geomatic methods applied to the change study of the la Paúl Rock Glacier, Spanish Pyrenees

Producción CientíficaRock glaciers are one of the most important features of the mountain permafrost in the Pyrenees. La Paúl is an active rock glacier located in the north face of the Posets massif in the La Paúl glacier cirque (Spanish Pyrenees). This study presents the preliminary results of the La Paúl rock glacier monitoring works carried out through two geomatic technologies since 2013: Global Navigation Satellite System (GNSS) receivers and Terrestrial Laser Scanning (TLS) devices. Displacements measured on the rock glacier surface have demonstrated both the activity of the rock glacier and the utility of this equipment for the rock glaciers dynamic analysis. The glacier has exhibited the fastest displacements on its west side (over 35 cm yr-1), affected by the Little Ice Age, and frontal area (over 25 cm yr-1). As an indicator of permafrost in marginal environments and its peculiar morphology, La Paúl rock glacier encourages a more prolonged study and to the application of more geomatic techniques for its detailed analysis.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project CGL2015-68144-R)Junta de Extremadura - Fondo Europeo de Desarrollo Regional (project GR10071

Second harmonic Hamiltonian: Algebraic and Schrödinger approaches

We study in detail the behavior of the energy spectrum for the second harmonic generation (SHG) and a family of corresponding quasi-exactly solvable Schrödinger potentials labeled by a real parameter b. The eigenvalues of this system are obtained by the polynomial deformation of the Lie algebra representation space. We have found the bi-confluent Heun equation (BHE) corresponding to this system in a differential realization approach, by making use of the symmetries. By means of a b-transformation from this second-order equation to a Schrödinger one, we have found a family of quasi-exactly solvable potentials. For each invariant n-dimensional subspace of the second harmonic generation, there are either n potentials, each with one known solution, or one potential with n-known solutions. Well-known potentials like a sextic oscillator or that of a quantum dot appear among them

Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathogen Fusarium circinatum

Producción CientíficaFusarium circinatum is a harmful pathogenic fungus mostly attacking Pinus species and also Pseudotsuga menziesii, causing cankers in trees of all ages, damping-of in seedlings, and mortality in cuttings and mother plants for clonal production. This fungus is listed as a quarantine pest in several parts of the world and the trade of potentially contaminated pine material such as cuttings, seedlings or seeds is restricted in order to prevent its spread to disease-free areas. Inspection of plant material often relies on DNA testing and several conventional or real-time PCR based tests targeting F. circinatum are available in the literature. In this work, an international collaborative study joined 23 partners to assess the transferability and the performance of nine molecular protocols, using a wide panel of DNA from 71 representative strains of F. circinatum and related Fusarium species. Diagnostic sensitivity, specifcity and accuracy of the nine protocols all reached values >80%, and the diagnostic specifcity was the only parameter difering signifcantly between protocols.The rates of false positives and of false negatives were computed and only the false positive rates difered signifcantly, ranging from 3.0% to 17.3%.The diference between protocols for some ofthe performance values were mainly due to cross-reactions with DNA from non-target species, which were either not tested or documented in the original articles. Considering that participating laboratories were free to use their own reagents and equipment, this study demonstrated that the diagnostic protocols for F. circinatum were not easily transferable to endusers. More generally, our results suggest that the use of protocols using conventional or real-time PCR outside their initial development and validation conditions should require careful characterization of the performance data priorto use under modifed conditions (i.e. reagents and equipment). Suggestions to improve the transfer are proposed.European Cooperation in Science and Technology (COST Action FP1406 PINESTRENGTH)Estonian Science Foundation (grants PSG136 and IUT21-04)Centro de Estudios do Ambiente e do Mar (CESAM) (projects UID/AMB/50017/2013 and POCI-01- 0145- FEDER-007638)Slovenian Research Agency (project P4-0107

Numerical study of the incompressible flow around a particle with roughness

Estudio mediante simulación en el programa CFD de una partícula con forma de cilindro circular por la que pasa un flujo incomprensible. Inicialmente, se realiza el estudio de la partícula con superficie perfectamente lisa para números de Reynolds de 80 y 240. Posteriormente se hace el estudio de esa misma partícula con diferentes rugosidades, variando en la superficie la frecuencia en unos casos y el radio en otros, de nuevo para los números de Reynolds de 80 y 240. Al comparar los resultados obtenidos de la partícula lisa con las partículas con variación de radio o variación de frecuencia en su superficie, se observa como el coeficiente de arrastre, coeficiente principal a tener en cuenta, aumenta cada vez más conforme se le va añadiendo una rugosidad mayor a la partícula. Otros coeficientes como el de presión, el de elevación y la velocidad, también son estudiados.The mainobjectiveisthestudyofacircularcylinderwhenthecylinderhasawavywall.Forthis reason, thein uenceofachangeinfrequencyandradiusforthecylinderwallareinvestigated. FlowswithReynoldsnumbersof80and240forthecircularcylinderwithasmoothwallhavebeen calculated asabenchmark.Thevaluesobtainedarecomparedwithacircularcylinderwithwavywall, namely,withthein uenceofthechangesinfrequencyandradiusmentionedaboveforthecylinder wall.Whereonecanseehowtheparametersstudiedmovefurtherandfurtherawayfromthevalues of thecircularcylinderwithasmoothwallwhentheroughnessincreases.Departamento de Ingeniería Energética y FluidomecánicaMáster en Ingeniería Industria

The Birman-Schwinger Operator for a Parabolic Quantum Well in a Zero-Thickness Layer in the Presence of a Two-Dimensional Attractive Gaussian Impurity

Producción CientíficaVer abstrac

Characterization of small RNAs originating from mitoviruses infecting the conifer pathogen Fusarium circinatum

Producción CientíficaDeep sequencing of small RNAs has proved efective in the diagnosis of mycovirus infections. In this study, the presence of mycoviruses in ten isolates of the phytopathogenic fungus Fusarium circinatum was investigated by high-throughput sequencing (HTS) of small RNAs. The contigs resulting from de novo assembly of the reads were aligned to viral genome sequences. The presence of each mycovirus detected in the isolates was confrmed by RT-PCR analysis with four previously described primer pairs and seven new pairs designed on the basis of sequencing data. The fndings demonstrate the potential use of HTS for reconstructing previously identifed mitoviruses infecting F. circinatum.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project AGL2015-69370-R)Ministerio de Economía, Industria y Competitividad (project AGL2012-39912)European Cooperation in Science and Technology (COST Action FP1406 PINESTRENGTH)Junta de Castilla y León (grant ORDEN EDU/1083/2013

Quantum error-correcting codes from algebraic geometry codes of Castle type

Producción CientíficaWe study Algebraic Geometry codes producing quantum error-correcting codes by the CSS construction. We pay particular attention to the family of Castle codes. We show that many of the examples known in the literature in fact belong to this family of codes. We systematize these constructions by showing the common theory that underlies all of them.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (grant MTM2015-65764-C3-1-P)Brazilian National Council for Scientific and Technological Development (grants 201584/2015-8 and 308326/2014-8

The mechanics of solid-state nanofoaming

Solid-state nanofoaming experiments are conducted on two polymethyl methacrylate (PMMA) grades of markedly different molecular weight using CO2 as the blowing agent. The sensitivity of porosity to foaming time and foaming temperature is measured. Also, the microstructure of the PMMA nanofoams is characterized in terms of cell size and cell nucleation density. A one-dimensional numerical model is developed to predict the growth of spherical, gas-filled voids during the solid-state foaming process. Diffusion of CO2 within the PMMA matrix is sufficiently rapid for the concentration of CO2 to remain almost uniform spatially. The foaming model makes use of experimentally calibrated constitutive laws for the uniaxial stress versus strain response of the PMMA grades as a function of strain rate and temperature, and the effect of dissolved CO2 is accounted for by a shift in the glass transition temperature of the PMMA. The maximum achievable porosity is interpreted in terms of cell wall tearing and comparisons are made between the predictions of the model and nanofoaming measurements; it is deduced that the failure strain of the cell walls is sensitive to cell wall thicknes