Comparison of Bisulfite Pyrosequencing and Methylation-Specific qPCR for Methylation Assessment

Different methodological approaches are available to assess DNA methylation biomarkers. In this study, we evaluated two sodium bisulfite conversion-dependent methods, namely pyrosequencing and methylation-specific qPCR (MS-qPCR), with the aim of measuring the closeness of agreement of methylation values between these two methods and its effect when setting a cut-off. Methylation of tumor suppressor gene p16/INK4A was evaluated in 80 lung cancer patients from which cytological lymph node samples were obtained. Cluster analyses were used to establish methylated and unmethylated groups for each method. Agreement and concordance between pyrosequencing and MS-qPCR was evaluated with Pearson's correlation, Bland-Altman, Cohen's kappa index and ROC curve analyses. Based on these analyses, cut-offs were derived for MS-qPCR. An acceptable correlation (Pearson's R2 = 0.738) was found between pyrosequencing (PYRmean) and MS-qPCR (NMP; normalized methylation percentage), providing similar clinical results when categorizing data as binary using cluster analysis. Compared to pyrosequencing, MS-qPCR tended to underestimate methylation for values between 0 and 15%, while for methylation >30% overestimation was observed. The estimated cut-off for MS-qPCR data based on cluster analysis, kappa-index agreement and ROC curve analysis were much lower than that derived from pyrosequencing. In conclusion, our results indicate that independently of the approach used for estimating the cut-off, the methylation percentage obtained through MS-qPCR is lower than that calculated for pyrosequencing. These differences in data and therefore in the cut-off should be examined when using methylation biomarkers in the clinical practice

New hydrogen-like potentials

Using the modified factorization method introduced by Mielnik, we construct a new class of radial potentials whose spectrum for l=0 coincides exactly with that of the hydrogen atom. A limiting case of our family coincides with the potentials previously derived by Abraham and MosesComment: 6 pages, latex, 2 Postscript figure

Estructuraci?n econ?mica y financiera de un instrumento de participaci?n en negocios forestales : el caso de la teca en la regi?n San Mart?n

El Per? tiene unas condiciones naturales que le otorgan una gran biodiversidad e importante riqueza biol?gica, hecho que genera ventajas comparativas en sectores como el forestal. Este libro analiza el caso espec?fico del ?rbol de teca, cuya siembra es favorecida por el clima propicio de nuestro pa?s y cuya madera, clasificada como frondosa tropical, se caracteriza por su solidez, resistencia, trabajabilidad y calidades est?ticas. Considerando que, seg?n la FAO (Organizaci?n de las Naciones Unidas para la Alimentaci?n y la Agricultura), existe un aumento de la demanda mundial de madera y una disminuci?n de la oferta, el consiguiente incremento del precio hace que un proyecto de reforestaci?n sobre la base de la teca sea econ?micamente rentable en el largo plazo. De manera que, en la presente investigaci?n realizada para llevar a cabo un proyecto de negocio forestal, se ha seleccionado la teca como la m?s adecuada debido a su considerable horizonte de recuperaci?n de la inversi?n y su alto valor en el mercado. Adem?s, muchos inversionistas est?n buscando oportunidades de negocios m?s rentables que una cuenta de ahorros o alg?n otro producto financiero a largo plazo --como los bonos ajustados por riesgo-- en el mercado de capitales peruano. Por ello, este estudio tiene como objetivo principal estructurar un modelo de financiamiento para plantaciones de teca, empleando un certificado de participaci?n fiduciario dirigido a personas naturales que busquen una rentabilidad de largo plazo para su inversi?n. Con este trabajo se espera verificar la viabilidad t?cnica, econ?mica y financiera del proyecto en un horizonte de 24 a?os

Plan de negocio para la viabilidad comercial, operativa y econ?mica en la implementaci?n de un gimnasio para bebes de 4 meses a ni?os de 5 a?os, en Lima Norte

La obesidad en los ni?os representa un problema a largo plazo, afectando su salud al incrementarse el riesgo de padecer enfermedades cardiovasculares o diabetes; se recomienda desde la etapa infantil, una correcta alimentaci?n y una actividad f?sica frecuente, desarrollando h?bitos saludables. En ese sentido, la siguiente propuesta es un plan de negocio para implementar un gimnasio para bebes de 4 meses a 5 a?os en Lima Norte, considerando la importante tasa de crecimiento en este sector de la poblaci?n, determinando como mercado objetivo madres de los NSE B y C, de los distritos de Comas, San Mart?n de Porres, Los Olivos e Independencia. Del estudio de mercado se ha identificado una demanda potencial de servicios que contribuyan al desarrollo infantil y no se conocen gimnasios para ni?os menores de 5 a?os. La propuesta de valor del gimnasio Baby Gym es ofrecer el servicio de gimnasio para a trav?s de un ambiente l?dico se fortalezcan habilidades al propio ritmo de cada ni?o. Con una inversi?n inicial estimada de S/. 164,100.00 y un periodo de an?lisis de 10 a?os, se obtiene un VAN = S/. 96,977 y TIR de 29.3% respectivamente, con lo cual, el an?lisis financiero concluye que el negocio es viable

Absence of Fragmentation in Two-Dimensional Bose-Einstein Condensation

We investigate the possibility that the BEC-like phenomena recently detected on two-dimensional finite trapped systems consist of fragmented condensates. We derive and diagonalize the one-body density matrix of a two-dimensional isotropically trapped Bose gas at finite temperature. For the ideal gas, the procedure reproduces the exact harmonic-oscillator eigenfunctions and the Bose distribution. We use a new collocation-minimization method to study the interacting gas in the Hartree-Fock approximation and obtain a ground-state wavefunction and condensate fraction consistent with those obtained by other methods. The populations of the next few eigenstates increase at the expense of the ground state but continue to be negligible; this supports the conclusion that two-dimensional BEC is into a single state.Comment: 6 pages, 1 figur

Controlling crystallization and its absence: Proteins, colloids and patchy models

The ability to control the crystallization behaviour (including its absence) of particles, be they biomolecules such as globular proteins, inorganic colloids, nanoparticles, or metal atoms in an alloy, is of both fundamental and technological importance. Much can be learnt from the exquisite control that biological systems exert over the behaviour of proteins, where protein crystallization and aggregation are generally suppressed, but where in particular instances complex crystalline assemblies can be formed that have a functional purpose. We also explore the insights that can be obtained from computational modelling, focussing on the subtle interplay between the interparticle interactions, the preferred local order and the resulting crystallization kinetics. In particular, we highlight the role played by ``frustration'', where there is an incompatibility between the preferred local order and the global crystalline order, using examples from atomic glass formers and model anisotropic particles.Comment: 11 pages, 7 figure

Self-recognition and Ca2+-dependent carbohydrate–carbohydrate cell adhesion provide clues to the Cambrian explosion

Author Posting. © The Authors, 2009. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Molecular Biology and Evolution 26 (2009): 2551-2561, doi:10.1093/molbev/msp170.The Cambrian explosion of life was a relatively short period ca. 540 million years ago that marked a generalized acceleration in the evolution of most animal phyla, but the trigger of this key biological event remains elusive. Sponges are the oldest extant Precambrian metazoan phylum and thus a valid model to study factors that could have unleashed the rise of multicellular animals. One such factor is the advent of self/non-self recognition systems, which would be evolutionarily beneficial to organisms to prevent germ cell parasitism or the introduction of deleterious mutations resulting from fusion with genetically different individuals. However, the molecules responsible for allorecognition probably evolved gradually before the Cambrian period, and some other (external) factor remains to be identified as the missing triggering event. Sponge cells associate through calcium-dependent, multivalent carbohydrate-carbohydrate interactions of the g200 glycan found on extracellular proteoglycans. Single molecule force spectroscopy analysis of g200-g200 binding indicates that calcium affects the lifetime (+Ca/-Ca: 680 s/3 s) and bond reaction length (+Ca/-Ca: 3.47 Å/2.27 Å). Calculation of mean g200 dissociation times in low and high calcium within the theoretical framework of a cooperative binding model indicates the non-linear and divergent characteristics leading to either disaggregated cells or stable multicellular assemblies, respectively. This fundamental phenomenon can explain a switch from weak to strong adhesion between primitive metazoan cells caused by the well documented rise in ocean calcium levels at the end of Precambrian time. We propose that stronger cell adhesion allowed the integrity of genetically uniform animals composed only of “self” cells, facilitating genetic constitutions to remain within the metazoan individual and be passed down inheritance lines. The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self/non-self recognition, and of a surge in sea water calcium that increased the binding forces between their calcium-dependent cell adhesion molecules.D.A. and A.K. acknowledge financial support from the Collaborative Research Center SFB 613 from the Deutsche Forschungsgemeinschaft (DFG), and X.F.-B. acknowledges financial support from grants BIO2002-00128, BIO2005-01591, and CSD2006-00012 from the Ministerio de Ciencia y Tecnología, Spain, which included Fondo Europeo de Desarrollo Regional funds, and from grant 2005SGR-00037 from the Generalitat de Catalunya, Spain