Optimal branching asymmetry of hydrodynamic pulsatile trees

Most of the studies on optimal transport are done for steady state regime conditions. Yet, there exists numerous examples in living systems where supply tree networks have to deliver products in a limited time due to the pulsatile character of the flow. This is the case for mammals respiration for which air has to reach the gas exchange units before the start of expiration. We report here that introducing a systematic branching asymmetry allows to reduce the average delivery time of the products. It simultaneously increases its robustness against the unevitable variability of sizes related to morphogenesis. We then apply this approach to the human tracheobronchial tree. We show that in this case all extremities are supplied with fresh air, provided that the asymmetry is smaller than a critical threshold which happens to fit with the asymmetry measured in the human lung. This could indicate that the structure is adjusted at the maximum asymmetry level that allows to feed all terminal units with fresh air.Comment: 4 pages, 4 figure

Spin Chirality in a Molecular Dysprosium Triangle: the Archetype of the Non-Collinear Ising Model

Single crystal magnetic studies combined with a theoretical analysis show that cancellation of the magnetic moments in the trinuclear Dy3+ cluster [Dy3(OH)2L3Cl(H2O)5]Cl3, resulting in a non-magnetic ground doublet, originates from the non-collinearity of the single ion easy axes of magnetization of the Dy3+ ions that lie in the plane of the triangle at 120 (deg.) one from each other. This gives rise to a peculiar chiral nature of the ground non-magnetic doublet and to slow relaxation of the magnetization with abrupt accelerations at the crossings of the discrete energy levels.Comment: 4 pages and 5 figure

Spin canting in a Dy-based Single-Chain Magnet with dominant next-nearest neighbor antiferromagnetic interactions

We investigate theoretically and experimentally the static magnetic properties of single crystals of the molecular-based Single-Chain Magnet (SCM) of formula [Dy(hfac)$_{3}$NIT(C$_{6}$H$_{4}$OPh)]$_{\infty}$ comprising alternating Dy$^{3+}$ and organic radicals. A peculiar inversion between maxima and minima in the angular dependence of the magnetic molar susceptibility $\chi_{M}$ occurs on increasing temperature. Using information regarding the monomeric building block as well as an {\it ab initio} estimation of the magnetic anisotropy of the Dy$^{3+}$ ion, this anisotropy-inversion phenomenon can be assigned to weak one-dimensional ferromagnetism along the chain axis. This indicates that antiferromagnetic next-nearest-neighbor interactions between Dy$^{3+}$ ions dominate, despite the large Dy-Dy separation, over the nearest-neighbor interactions between the radicals and the Dy$^{3+}$ ions. Measurements of the field dependence of the magnetization, both along and perpendicularly to the chain, and of the angular dependence of $\chi_{M}$ in a strong magnetic field confirm such an interpretation. Transfer matrix simulations of the experimental measurements are performed using a classical one-dimensional spin model with antiferromagnetic Heisenberg exchange interaction and non-collinear uniaxial single-ion anisotropies favoring a canted antiferromagnetic spin arrangement, with a net magnetic moment along the chain axis. The fine agreement obtained with experimental data provides estimates of the Hamiltonian parameters, essential for further study of the dynamics of rare-earths based molecular chains.Comment: 11 pages, 8 figure

JWalk: a tool for lazy, systematic testing of java classes by design introspection and user interaction

Popular software testing tools, such as JUnit, allow frequent retesting of modified code; yet the manually created test scripts are often seriously incomplete. A unit-testing tool called JWalk has therefore been developed to address the need for systematic unit testing within the context of agile methods. The tool operates directly on the compiled code for Java classes and uses a new lazy method for inducing the changing design of a class on the fly. This is achieved partly through introspection, using Java’s reflection capability, and partly through interaction with the user, constructing and saving test oracles on the fly. Predictive rules reduce the number of oracle values that must be confirmed by the tester. Without human intervention, JWalk performs bounded exhaustive exploration of the class’s method protocols and may be directed to explore the space of algebraic constructions, or the intended design state-space of the tested class. With some human interaction, JWalk performs up to the equivalent of fully automated state-based testing, from a specification that was acquired incrementally

Selection rules for Single-Chain-Magnet behavior in non-collinear Ising systems

The magnetic behavior of molecular Single-Chain Magnets is investigated in the framework of a one-dimensional Ising model with single spin-flip Glauber dynamics. Opportune modifications to the original theory are required in order to account for reciprocal non-collinearity of local anisotropy axes and the crystallographic (laboratory) frame. The extension of Glauber's theory to the case of a collinear Ising ferrimagnetic chain is also discussed. Within this formalism, both the dynamics of magnetization reversal in zero field and the response of the system to a weak magnetic field, oscillating in time, are studied. Depending on the geometry, selection rules are found for the occurrence of slow relaxation of the magnetization at low temperatures, as well as for resonant behavior of the a.c. susceptibility as a function of temperature at low frequencies. The present theory applies successfully to some real systems, namely Mn-, Dy-, and Co-based molecular magnetic chains, showing that Single-Chain-Magnet behavior is not only a feature of collinear ferro- and ferrimagnetic, but also of canted antiferromagnetic chains.Comment: 15 pages, 6 figure

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Modeling stochasticity and robustness in gene regulatory networks

Motivation: Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations

On the complexity of acyclic modules in automata networks

Modules were introduced as an extension of Boolean automata networks. They have inputs which are used in the computation said modules perform, and can be used to wire modules with each other. In the present paper we extend this new formalism and study the specific case of acyclic modules. These modules prove to be well described in their limit behavior by functions called output functions. We provide other results that offer an upper bound on the number of attractors in an acyclic module when wired recursively into an automata network, alongside a diversity of complexity results around the difficulty of deciding the existence of cycles depending on the number of inputs and the size of said cycle.Comment: 21 page

Analysis of MEFV exon methylation and expression patterns in familial Mediterranean fever

<p>Abstract</p> <p>Background</p> <p>MEFV mutations and decreased expression level of the gene are related to FMF pathology. DNA methylation at CpG islands is a well-known mechanism for transcriptional silencing. MEFV has a CpG island, spanning a part of the first intron and the whole of the second exon of the gene covering 998 bp region. Here, we tested the hypothesis that the MEFV transcript level in FMF patients correlates with its methylation level, and methylation, by allowing transcription silencing, has a role in FMF ethiopathogenesis.</p> <p>Methods</p> <p>The study group was composed of pediatric FMF patients (N = 51) and age-gender matched healthy controls (N = 21). The relative expression level of MEFV was assessed via quantitative real-time PCR (qRT-PCR) and bisulfite sequencing (BS) was performed to analyse the methylation level quantitatively.</p> <p>Results</p> <p>MEFV expression in FMF patients were decreased compared to healthy controls (<it>P </it>= 0.031). Methylation level of exon 2 of MEFV was found to be slightly higher in FMF patients compared to healthy controls (76% versus 74%) (<it>P </it>= 0.049). The expression level of the MEFV was negatively correlated with the methylation level of the CpG island in both FMF and healthy controls groups (cor = -0.29, <it>P </it>= 0.041) but more so in the FMF only group (cor = -0.36, <it>P </it>= 0.035).</p> <p>Conclusions</p> <p>In this study, the relation between reduced MEFV expression level and FMF was confirmed. Observed slight increase in methylation in FMF patients, and correlation of methylation with expression might be indicative of its role in FMF, however a larger dataset is needed to confirm our preliminary findings.</p