Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

Background: During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia.

Modelling leaf development in Oxalis latifolia

This study was carried to develop functions that could explain the growth of Oxalis latifolia, in both early stages and throughout the season, contributing to the improvement of its cultural control. Bulbs of the Cornwall form of O. latifolia were buried at 1 and 8 cm in March 1999 and 2000. Samples were destructive at fixed times, and at each time the corresponding BBCH scale codes as well as the absolute number of growing and adult leaves were noted. Using the absolute number of adult leaves (transformed to percentages), a Gaussian curve of three parameters that explains the growth during the season (R2=0.9355) was developed. The BBCH scale permitted the fit of two regression lines that were accurately adjusted for each burial depth (R2=0.9969 and R2=0.9930 respectively for 1 and 8 cm). The best moment for an early defoliation in Northern Spain could be calculated with these regression lines, and was found to be the second week of May. In addition, it was observed that a burial depth of 8 cm does not affect the growing pattern of the weed, but it affects the number of leaves they produce, which decreases to less than a half of those produced at 1 cm.

Mutations in NDUFB11, Encoding a Complex I Component of the Mitochondrial Respiratory Chain, Cause Microphthalmia with Linear Skin Defects Syndrome.

Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations.

Integrability of a linear center perturbed by a fourth degree homogeneous polynomial

In this work we study the integrability of a two-dimensional autonomous system in the plane with linear part of center type and non-linear part given by homogeneous polynomials of fourth degree. We give sufficient conditions for integrability in polar coordinates. Finally we establish a conjecture about the independence of the two classes of parameters which appear in the system; if this conjecture is true the integrable cases found will be the only possible ones.

Integrability of a linear center perturbed by a fifth degree homogeneous polynomial

In this work we study the integrability of two-dimensional autonomous system in the plane with linear part of center type and non-linear part given by homogeneous polynomials of fifth degree. We give a simple characterisation for the integrable cases in polar coordinates. Finally we formulate a conjecture about the independence of the two classes of parameters which appear on the system; if this conjecture is true the integrable cases found will be the only possible ones.

Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

Background: Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results: Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions: Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

Definition of linear color models in the RGB vector color space to detect red peaches in orchard images taken under natural illumination

This work proposes the detection of red peaches in orchard images based on the definition of different linear color models in the RGB vector color space. The classification and segmentation of the pixels of the image is then performed by comparing the color distance from each pixel to the different previously defined linear color models. The methodology proposed has been tested with images obtained in a real orchard under natural light. The peach variety in the orchard was the paraguayo (Prunus persica var. platycarpa) peach with red skin. The segmentation results showed that the area of the red peaches in the images was detected with an average error of 11.6%; 19.7% in the case of bright illumination; 8.2% in the case of low illumination; 8.6% for occlusion up to 33%; 12.2% in the case of occlusion between 34 and 66%; and 23% for occlusion above 66%. Finally, a methodology was proposed to estimate the diameter of the fruits based on an ellipsoidal fitting. A first diameter was obtained by using all the contour pixels and a second diameter was obtained by rejecting some pixels of the contour. This approach enables a rough estimate of the fruit occlusion percentage range by comparing the two diameter estimates.

Affinity distribution functions in multicomponent heterogeneous adsorption. Analytical inversion of isotherms to obtain affinity spectra

An analytical approach for the interpretation of multicomponent heterogeneous adsorption or complexation isotherms in terms of multidimensional affinity spectra is presented. Fourier transform, applied to analyze the corresponding integral equation, leads to an inversion formula which allows the computation of the multicomponent affinity spectrum underlying a given competitive isotherm. Although a different mathematical methodology is used, this procedure can be seen as the extension to multicomponent systems of the classical Sips’s work devoted to monocomponent systems. Furthermore, a methodology which yields analytical expressions for the main statistical properties (mean free energies of binding and covariance matrix) of multidimensional affinity spectra is reported. Thus, the level of binding correlation between the different components can be quantified. It has to be highlighted that the reported methodology does not require the knowledge of the affinity spectrum to calculate the means, variances, and covariance of the binding energies of the different components. Nonideal competitive consistent adsorption isotherm, widely used in metal/proton competitive complexation to environmental macromolecules, and Frumkin competitive isotherms are selected to illustrate the application of the reported results. Explicit analytical expressions for the affinity spectrum as well as for the matrix correlation are obtained for the NICCA case. © 2004 American Institute of Physics.

New insights into cellular prion protein (PrPc) functions: the 'ying and yang' of a relevant protein.

The conversion of cellular prion protein (PrPc), a GPI-anchored protein, into a protease-K-resistant and infective form (generally termed PrPsc) is mainly responsible for Transmissible Spongiform Encephalopathies (TSEs), characterized by neuronal degeneration and progressive loss of basic brain functions. Although PrPc is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. Recent studies have confirmed its participation in basic physiological processes such as cell proliferation and the regulation of cellular homeostasis. Other studies indicate that PrPc interacts with several molecules to activate signaling cascades with a high number of cellular effects. To determine PrPc functions, transgenic mouse models have been generated in the last decade. In particular, mice lacking specific domains of the PrPc protein have revealed the contribution of these domains to neurodegenerative processes. A dual role of PrPc has been shown, since most authors report protective roles for this protein while others describe pro-apoptotic functions. In this review, we summarize new findings on PrPc functions, especially those related to neural degeneration and cell signaling.

A Database of >20 keV Electron Green's Functions of Interplanetary Transport at 1 AU

We use interplanetary transport simulations to compute a database of electron Green's functions, i.e., differential intensities resulting at the spacecraft position from an impulsive injection of energetic (>20 keV) electrons close to the Sun, for a large number of values of two standard interplanetary transport parameters: the scattering mean free path and the solar wind speed. The nominal energy channels of the ACE, STEREO, and Wind spacecraft have been used in the interplanetary transport simulations to conceive a unique tool for the study of near-relativistic electron events observed at 1 AU. In this paper, we quantify the characteristic times of the Green's functions (onset and peak time, rise and decay phase duration) as a function of the interplanetary transport conditions. We use the database to calculate the FWHM of the pitch-angle distributions at different times of the event and under different scattering conditions. This allows us to provide a first quantitative result that can be compared with observations, and to assess the validity of the frequently used term beam-like pitch-angle distribution.

Protein interaction studies point to new functions for Escherichia coli glyceraldehyde-3-phosphate dehydrogenase

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a multifunctional protein with defined functions in numerous mammalian cellular processes. GAPDH functional diversity depends on various factors such as covalent modifications, subcellular localization, oligomeric state and intracellular concentration of substrates or ligands, as well as protein-protein interactions. In bacteria, alternative GAPDH functions have been associated with its extracellular location in pathogens or probiotics. In this study, new intracellular functions of E. coli GAPDH were investigated following a proteomic approach aimed at identifying interacting partners using in vivo formaldehyde cross-linking followed by mass spectrometry. The identified proteins were involved in metabolic processes, protein synthesis and folding or DNA repair. Some interacting proteins were also identified in immunopurification experiments in the absence of cross-linking. Pull-down experiments and overlay immunoblotting were performed to further characterize the interaction with phosphoglycolate phosphatase (Gph). This enzyme is involved in the metabolism of 2-phosphoglycolate formed in the DNA repair of 3"-phosphoglycolate ends generated by bleomycin damage. We show that interaction between Gph and GAPDH increases in cells challenged with bleomycin, suggesting involvement of GAPDH in cellular processes linked to DNA repair mechanisms.

Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity

Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC).

Counter-propagating dual-trap optical tweezers based on linear momentum conservation

We present a dual-trap optical tweezers setup which directly measures forces using linear momentum conservation. The setup uses a counter-propagating geometry, which allows momentum measurement on each beam separately. The experimental advantages of this setup include low drift due to all-optical manipulation, and a robust calibration (independent of the features of the trapped object or buffer medium) due to the force measurement method. Although this design does not attain the high-resolution of some co-propagating setups, we show that it can be used to perform different single molecule measurements: fluctuation-based molecular stiffness characterization at different forces and hopping experiments on molecular hairpins. Remarkably, in our setup it is possible to manipulate very short tethers (such as molecular hairpins with short handles) down to the limit where beads are almost in contact. The setup is used to illustrate a novel method for measuring the stiffness of optical traps and tethers on the basis of equilibrium force fluctuations, i.e., without the need of measuring the force vs molecular extension curve. This method is of general interest for dual trap optical tweezers setups and can be extended to setups which do not directly measure forces.

Anticipating linear stochastic differential equations driven by a Lévy process

In this paper we study the existence of a unique solution for linear stochastic differential equations driven by a Lévy process, where the initial condition and the coefficients are random and not necessarily adapted to the underlying filtration. Towards this end, we extend the method based on Girsanov transformations on Wiener space and developped by Buckdahn [7] to the canonical Lévy space, which is introduced in [25].