Multicriteria global optimization for biocircuit design

One of the challenges in Synthetic Biology is to design circuits with increasing levels of complexity. While circuits in Biology are complex and subject to natural tradeoffs, most synthetic circuits are simple in terms of the number of regulatory regions, and have been designed to meet a single design criterion. In this contribution we introduce a multiobjective formulation for the design of biocircuits. We set up the basis for an advanced optimization tool for the modular and systematic design of biocircuits capable of handling high levels of complexity and multiple design criteria. Our methodology combines the efficiency of global Mixed Integer Nonlinear Programming solvers with multiobjective optimization techniques. Through a number of examples we show the capability of the method to generate non intuitive designs with a desired functionality setting up a priori the desired level of complexity. The presence of more than one competing objective provides a realistic design setting where every design solution represents a trade-off between different criteria. The tool can be useful to explore and identify different design principles for synthetic gene circuits

Emc aerospace systems analysis Interim scientific report

Analysis and data requirements for solving potential aerospace electromagnetic compatibility problem

Forelimb muscle and joint actions in Archosauria: insights from Crocodylus johnstoni (Pseudosuchia) and Mussaurus patagonicus (Sauropodomorpha)

Many of the major locomotor transitions during the evolution of Archosauria, the lineage including crocodiles and birds as well as extinct Dinosauria, were shifts from quadrupedalism to bipedalism (and vice versa). Those occurred within a continuum between more sprawling and erect modes of locomotion and involved drastic changes of limb anatomy and function in several lineages, including sauropodomorph dinosaurs. We present biomechanical computer models of two locomotor extremes within Archosauria in an analysis of joint ranges of motion and the moment arms of the major forelimb muscles in order to quantify biomechanical differences between more sprawling, pseudosuchian (represented the crocodile Crocodylus johnstoni) and more erect, dinosaurian (represented by the sauropodomorph Mussaurus patagonicus) modes of forelimb function. We compare these two locomotor extremes in terms of the reconstructed musculoskeletal anatomy, ranges of motion of the forelimb joints and the moment arm patterns of muscles across those ranges of joint motion. We reconstructed the three-dimensional paths of 30 muscles acting around the shoulder, elbow and wrist joints. We explicitly evaluate how forelimb joint mobility and muscle actions may have changed with postural and anatomical alterations from basal archosaurs to early sauropodomorphs. We thus evaluate in which ways forelimb posture was correlated with muscle leverage, and how such differences fit into a broader evolutionary context (i.e. transition from sprawling quadrupedalism to erect bipedalism and then shifting to graviportal quadrupedalism). Our analysis reveals major differences of muscle actions between the more sprawling and erect models at the shoulder joint. These differences are related not only to the articular surfaces but also to the orientation of the scapula, in which extension/flexion movements in Crocodylus (e.g. protraction of the humerus) correspond to elevation/depression in Mussaurus. Muscle action is highly influenced by limb posture, more so than morphology. Habitual quadrupedalism in Mussaurus is not supported by our analysis of joint range of motion, which indicates that glenohumeral protraction was severely restricted. Additionally, some active pronation of the manus may have been possible in Mussaurus, allowing semi-pronation by a rearranging of the whole antebrachium (not the radius against the ulna, as previously thought) via long-axis rotation at the elbow joint. However, the muscles acting around this joint to actively pronate it may have been too weak to drive or maintain such orientations as opposed to a neutral position in between pronation and supination. Regardless, the origin of quadrupedalism in Sauropoda is not only linked to manus pronation but also to multiple shifts of forelimb morphology, allowing greater flexion movements of the glenohumeral joint and a more columnar forelimb posture

Numerically flat Higgs vector bundles

After providing a suitable definition of numerical effectiveness for Higgs bundles, and a related notion of numerical flatness, in this paper we prove, together with some side results, that all Chern classes of a Higgs-numerically flat Higgs bundle vanish, and that a Higgs bundle is Higgs-numerically flat if and only if it is has a filtration whose quotients are flat stable Higgs bundles. We also study the relation between these numerical properties of Higgs bundles and (semi)stability.Comment: 11 page

Using Entheseal Length to Infer Locomotor Type

An enthesis is a marking (tuberosity or impression) on bone where a muscle or tendon attaches and it can be influenced by age, sex, physical activity, and muscle size. This study ascertains whether entheses, long bones, and their respective ratios can be used as an indicator for mode of locomotion in four primate species: Ateles geoffroyi (Geoffroy’s spider monkey), Colobus guereza (mantled guereza), Hylobates lar (lar gibbon), and Macaca mulatta (rhesus monkey). Seven entheses on four long bones were chosen based on importance of the muscle in relation to specific locomotor types, use in other studies, and ease of measurement; for each enthesis and accompanying long bone, a ratio was created which indicated the percentage of length the enthesis occupied on the long bone. Body length and not body mass was used in statistical analysis since a correlation analysis showed these two variables as having a significant, positive association. Comparisons were done among species, sex, and location (captive or wild caught specimen) using a Generalized Linear Model (GLM) with Tukey-Kramer’s tests and Student’s t-tests. The hypothesized pattern for results comparing species will be that C. guereza and M. mulatta group together, H. lar will be separate, and A. geoffroyi will be intermediate between H. lar and C. guereza/M. mulatta due to differences in their locomotion. Results show that five out of seven entheses, one out of four long bones, and one out of seven ratios follow the hypothesized pattern. Reasons for the discrepancy between the hypothesized pattern and results include body length and variable locomotor types within each species. Regarding sex, entheses are sexually dimorphic. Location was not a significant factor among species, which allowed captive and wild caught specimens to be combined into a larger sample. These results show that entheses are indicative of sex and are not affected by captivity. Overall, entheseal length is indicative of locomotor type, but long bone length and the ratio are not

MACOC: a medoid-based ACO clustering algorithm

The application of ACO-based algorithms in data mining is growing over the last few years and several supervised and unsupervised learning algorithms have been developed using this bio-inspired approach. Most recent works concerning unsupervised learning have been focused on clustering, showing great potential of ACO-based techniques. This work presents an ACO-based clustering algorithm inspired by the ACO Clustering (ACOC) algorithm. The proposed approach restructures ACOC from a centroid-based technique to a medoid-based technique, where the properties of the search space are not necessarily known. Instead, it only relies on the information about the distances amongst data. The new algorithm, called MACOC, has been compared against well-known algorithms (K-means and Partition Around Medoids) and with ACOC. The experiments measure the accuracy of the algorithm for both synthetic datasets and real-world datasets extracted from the UCI Machine Learning Repository

Variational bounds on the energy dissipation rate in body-forced shear flow

A new variational problem for upper bounds on the rate of energy dissipation in body-forced shear flows is formulated by including a balance parameter in the derivation from the Navier-Stokes equations. The resulting min-max problem is investigated computationally, producing new estimates that quantitatively improve previously obtained rigorous bounds. The results are compared with data from direct numerical simulations.Comment: 15 pages, 7 figure

Emission Quenching in Tetraphenylfuran Crystal: Why This Propeller-Shaped Molecule Does Not Emit in the Condensed Phase

Due to their substantial fluorescence quantum yields in the crystalline phase, propeller-shaped molecules have recently gained significant attention as potential emissive materials for optoelectronic applications. For the family of cyclopentadiene derivatives, light-emission is highly dependent on the nature of heteroatomic substitutions. In this paper, we investigate excited state relaxation pathways in the tetraphenyl-furan molecule (TPF), which in contrast with other molecules in the family, shows emission quenching in the solid-state. For the singlet manifold, our calculations show nonradiative pathways associated with C-O elongation are blocked in both vacuum and the solid state. A fraction of the population can be transferred to the triplet manifold and, subsequently, to the ground state in both phases. This process is expected to be relatively slow due to the small spin-orbit couplings between the relevant singlet-triplet states. Emission quenching in crystalline TPF seems to be in line with more efficient exciton hopping rates. Our simulations help clarify the role of conical intersections, population of the triplet states and crystalline structure in the emissive response of propeller-shaped molecules