Discussion required for correct interpretation

Thank you for the opportunity to comment on the editorial by Romero and colleagues [1], which raises a number of important and interesting questions. Such discussion is mandatory if results of scientific techniques such as gene array are to be correctly interpreted and used as the basis for future improvements in patient care

Dynamics of polydisperse irreversible adsorption: a pharmacological example

Many drug delivery systems suffer from undesirable interactions with the host immune system. It has been experimentally established that covalent attachment (irreversible adsorption) of suitable macromolecules to the surface of the drug carrier can reduce such undesirable interactions. A fundamental understanding of the adsorption process is still lacking. In this paper, the classical random irreversible adsorption model is generalized to capture certain essential processes involved in pharmacological applications, allowing for macromolecules of different sizes, partial overlapping of the tails of macromolecules, and the influence of reactions with the solvent on the adsorption process. Working in one dimension, an integro-differential evolution equation for the adsorption process is derived, and the asymptotic behavior of the surface area covered and the number of molecules attached to the surface are studied. Finally, equation-free dynamic renormalization tools are applied to study the asymptotically self-similar behavior of the adsorption statistics

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

BackgroundPreterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition.MethodsSamples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes.ResultsThe largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions.ConclusionsThe results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection

Realistic boundary conditions for stochastic simulations of reaction-diffusion processes

Many cellular and subcellular biological processes can be described in terms of diffusing and chemically reacting species (e.g. enzymes). Such reaction-diffusion processes can be mathematically modelled using either deterministic partial-differential equations or stochastic simulation algorithms. The latter provide a more detailed and precise picture, and several stochastic simulation algorithms have been proposed in recent years. Such models typically give the same description of the reaction-diffusion processes far from the boundary of the simulated domain, but the behaviour close to a reactive boundary (e.g. a membrane with receptors) is unfortunately model-dependent. In this paper, we study four different approaches to stochastic modelling of reaction-diffusion problems and show the correct choice of the boundary condition for each model. The reactive boundary is treated as partially reflective, which means that some molecules hitting the boundary are adsorbed (e.g. bound to the receptor) and some molecules are reflected. The probability that the molecule is adsorbed rather than reflected depends on the reactivity of the boundary (e.g. on the rate constant of the adsorbing chemical reaction and on the number of available receptors), and on the stochastic model used. This dependence is derived for each model.Comment: 24 pages, submitted to Physical Biolog

Spatial and spectral properties of the pulsed second-harmonic generation in a PP-KTP waveguide

Spatial and spectral properties of the pulsed second harmonic generation in a periodically-poled KTP waveguide exploiting simultaneously the first, second, and third harmonics of periodic nonlinear modulation are analyzed. Experimental results are interpreted using a model based on finite elements method. Correlations between spatial and spectral properties of the fundamental and second-harmonic fields are revealed. Individual nonlinear processes can be exploited combining spatial and spectral filtering. Also the influence of waveguide parameters to the second-harmonic spectra is addressed.Comment: 13 pages, 8 figure

F-term uplifting via consistent D-terms

The issue of fine-tuning necessary to achieve satisfactory degree of hierarchy between moduli masses, the gravitino mass and the scale of the cosmological constant has been revisited in the context of supergravities with consistent D-terms. We have studied (extended) racetrack models where supersymmetry breaking and moduli stabilisation cannot be separated from each other. We show that even in such cases the realistic hierarchy can be achieved on the expense of a single fine-tuning. The presence of two condensates changes the role of the constant term in the superpotential, W_0, and solutions with small vacuum energy and large gravitino mass can be found even for very small values of W_0. Models where D-terms are allowed to vanish at finite vevs of moduli fields - denoted `cancellable' D-terms - and the ones where D-terms may vanish only at infinite vevs of some moduli - denoted `non-cancellable' - differ markedly in their properties. It turns out that the tuning with respect to the Planck scale required in the case of cancellable D-terms is much weaker than in the case of non-cancellable ones. We have shown that, against intuition, a vanishing D-term can trigger F-term uplifting of the vacuum energy due to the stringent constraint it imposes on vacuum expectation values of charged fields. Finally we note that our models only rely on two dimensionful parameters: M_P and W_0.Comment: 10 pages, 2 figures, plain Latex, references adde

COMPUTATIONAL METHODOLOGY TO ANALYZE THE EFFECT OF MASS TRANSFER RATE ON ATTENUATION OF LEAKED CARBON DIOXIDE IN SHALLOW AQUIFERS

Exsolution and re-dissolution of CO2 gas within heterogeneous porous media are investigated using experimental data and mathematical modeling. In a set of bench-scale experiments, water saturated with CO2 under a given pressure is injected into a 2-D water-saturated porous media system, causing CO2 gas to exsolve and migrate upwards. A layer of fine sand mimicking a heterogeneity within a shallow aquifer is present in the tank to study accumulation and trapping of exsolved CO2. Then, clean water is injected into the system and the accumulated CO2 dissolves back into the flowing water. Simulated exsolution and dissolution mass transfer processes are studied using both nearequilibrium and kinetic approaches and compared to experimental data under conditions that do and do not include lateral background water flow. The mathematical model is based on the mixed hybrid finite element method that allows for accurate simulation of both advection- and diffusion- dominated processes

Stochastic modelling of reaction-diffusion processes: algorithms for bimolecular reactions

Several stochastic simulation algorithms (SSAs) have been recently proposed for modelling reaction-diffusion processes in cellular and molecular biology. In this paper, two commonly used SSAs are studied. The first SSA is an on-lattice model described by the reaction-diffusion master equation. The second SSA is an off-lattice model based on the simulation of Brownian motion of individual molecules and their reactive collisions. In both cases, it is shown that the commonly used implementation of bimolecular reactions (i.e. the reactions of the form A + B -> C, or A + A -> C) might lead to incorrect results. Improvements of both SSAs are suggested which overcome the difficulties highlighted. In particular, a formula is presented for the smallest possible compartment size (lattice spacing) which can be correctly implemented in the first model. This implementation uses a new formula for the rate of bimolecular reactions per compartment (lattice site).Comment: 33 pages, submitted to Physical Biolog

Conceptualizing organizational culture and business-IT alignment : a systematic literature review

For decades, business and information technology alignment has fascinated scholars and practitioners. However, understanding these alignment mechanisms is challenging. The significant role of information technology (IT) in digitalization and agile transformation calls for targeted management of the readiness and capability of IT as an enabler and strategic business partner. This paper assumes that organizational culture is a success factor for business-IT alignment. Therefore, it aims to explore the culture-alignment relationship by the following research questions: What are typical IT management organizational culture characteristics, and how do they contribute to business-IT alignment? The study conducts a systematic literature review. First, after defining the critical terms, it searches the databases indexed in the Web of Science, Scopus, and Google Scholar. Then, the study uses bibliometrics to get quantitative insights into the research topic. Finally, it investigates the key arguments and findings of the selected papers. The analyzed literature depicts the relationship between an IT management culture and business-IT alignment elements. However, the research lacks concrete modeling and conception. This article contributes to a better culture-alignment relationship interpretation and closes a gap in the body of knowledge by combining quantitative and qualitative literature review methods