ICRS-Filter: A randomized direct search algorithm for constrained nonconvex optimization problems

This work presents a novel algorithm and its implementation for the stochastic optimization of generally constrained Nonlinear Programming Problems (NLP). The basic algorithm adopted is the Iterated Control Random Search (ICRS) method of Casares and Banga (1987) with modifications such that random points are generated strictly within a bounding box defined by bounds on all variables. The ICRS algorithm serves as an initial point determination method for launching gradient-based methods that converge to the nearest local minimum. The issue of constraint handling is addressed in our work via the use of a filter based methodology, thus obviating the need for use of the penalty functions as in the basic ICRS method presented in Banga and Seider (1996),which handles only bound constrained problems. The proposed algorithm, termed ICRS-Filter, is shown to be very robust and reliable in producing very good or global solutions for most of the several case studies examined in this contribution.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.cherd.2015.12.00

A novel ladder-like lectin relates to sites of mucosal immunity in Atlantic Halibut (Hippoglossus hippoglossus L.)

A novel 27 kDa ladder-lectin-like protein, showing a multimeric structure under non-reducing conditions, was isolated from halibut serum by binding to N-acetyl glucosamine. Mass-spectrometry analysis did not show significant homology with known proteins. Specific antibodies were produced and used in immunohistochemistry on tissue sections of early halibut ontogeny from 119 until 1050 °d post hatching. A strong positive response was detected in the mucosal cells of the skin, gills and gut, indicating a role in the mucosal immune defence at these sites. Further immunopositivity was detected in liver, myeloma of kidney and the brain at different developmental stages but predominant expression was found in mucosal surfaces at later stages of development tested (1050 °d). It is still uncertain whether this ladder-like lectin forms part of the complement pathway, as a lectin or ficolin, or if it belongs to galectins. A strong detection in mucosal surfaces on skin, gills and gut, show similar patterns of expression as both mucosal lectins and galectins in other fish. Detection in neuronal tissue may indicate putative roles in tissue remodelling of brain and in ongoing neurogenesis in the fish eye

Starcounts Redivivus. IV. Density Laws Through Photometric Parallaxes

In an effort to more precisely define the spatial distribution of Galactic field stars, we present an analysis of the photometric parallaxes of 70,000 stars covering nearly 15 square degrees in seven Kapteyn Selected Areas. We address the affects of Malmquist Bias, subgiant/giant contamination, metallicity and binary stars upon the derived density laws. The affect of binary stars is the most significant. We find that while the disk-like populations of the Milky Way are easily constrained in a simultaneous analysis of all seven fields, no good simultaneous solution for the halo is found. We have applied halo density laws taken from other studies and find that the Besancon flattened power law halo model (c/a=0.6, r^-2.75) produces the best fit to our data. With this halo, the thick disk has a scale height of 750 pc with an 8.5% normalization to the old disk. The old disk scale height is 280-300 pc. Corrected for a binary fraction of 50%, these scale heights are 940 pc and 350-375 pc, respectively. Even with this model, there are systematic discrepancies between the observed and predicted density distributions. Our model produces density overpredictions in the inner Galaxy and density underpredictions in the outer Galaxy. A possible solution is modeling the stellar halo as a two-component system in which the halo has a flattened inner distribution and a roughly spherical, but substructured outer distribution. Further reconciliation could be provided by a flared thick disk, a structure consistent with a merger origin for that population. (Abridged)Comment: 66 pages, accepted to Astrophysical journal, some figures compresse

Smooth Entropy in Axiomatic Thermodynamics

Thermodynamics can be formulated in either of two approaches, the phenomenological approach, which refers to the macroscopic properties of systems, and the statistical approach, which describes systems in terms of their microscopic constituents. We establish a connection between these two approaches by means of a new axiomatic framework that can take errors and imprecisions into account. This link extends to systems of arbitrary sizes including very small systems, for which the treatment of imprecisions is pertinent to any realistic situation. Based on this, we identify the quantities that characterise whether certain thermodynamic processes are possible with entropy measures from information theory. In the error-tolerant case, these entropies are so-called smooth min and max entropies. Our considerations further show that in an appropriate macroscopic limit there is a single entropy measure that characterises which state transformations are possible. In the case of many independent copies of a system (the so-called i.i.d. regime), the relevant quantity is the von Neumann entropy. Transformations among microcanonical states are characterised by the Boltzmann entropy

A different approach for the estimation of Galactic model parameters

We estimated the Galactic model parameters by means of a new approach based on the comparison of the observed space density functions per absolute magnitude interval with a unique density law for each population individually, and via the procedure in situ for the field SA 114 ($l=68^{o}.15$, $b=-48^{o}.38$; 4.239 square-degree; J2000). The separation of stars into different populations has been carried out by their spatial distribution. The new approach reveals that model parameters are absolute magnitude dependent. The scale height for thin disk decreases monotonously from absolutely bright to absolutely faint stars in a range 265-495 pc, but there is a discontunity at the absolute magnitude $M(g^{'})=10$ where the squared secans hiperbolicus density law replaces the exponential one. The range of the scale-height for thick disk, dominant in the absolute magnitude interval $5<M(g^{'})\leq9$, is less: 805-970 pc. The local space density for thick disk relative to thin disk decreases from 9.5% to 5.2% when one goes from the absolutely bright to faint magnitudes. Halo is dominant in three absolute magnitude intervals and the axial ratio for this component is almost the same for these intervals where $c/a \sim 0.7$. The same holds for the local space density relative to the thin disk with range (0.02-0.15)%. The model parameters estimated by comparison of the observed space density functions combined for three populations per absolute magnitude interval with the combined density laws agree with the cited values in the literature. Also each parameter is equal to at least one of the corresponding parameters estimated for different absolute magnitude intervals by the new approach. We argue that the most appropriate Galactic model parameters are those, that are magnitude dependent.Comment: 14 pages, including 16 figures and 16 tables, accepted for publication in MNRA

Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts

Although circulating DNA (ctDNA) could be an attractive tool for early cancer detection, diagnosis, prognosis, monitoring or prediction of response to therapies, knowledge on its origin, form and rate of release is poor and often contradictory. Here, we describe an experimental system to systematically examine these aspects. Nude mice were xenografted with human HT29 or SW620 colorectal carcinoma (CRC) cells and ctDNA was analyzed by Q–PCR with highly specific and sensitive primer sets at different times post-graft. We could discriminate ctDNA from normal (murine) cells and from mutated and non-mutated tumor (human) cells by using species-specific KRAS or PSAT1 primers and by assessing the presence of the BRAF V600E mutation. The concentration of human (mutated and non-mutated) ctDNA increased significantly with tumor growth. Conversely, and differently from previous studies, low, constant level of mouse ctDNA was observed, thus facilitating the study of mutated and non-mutated tumor derived ctDNA. Finally, analysis of ctDNA fragmentation confirmed the predominance of low-size fragments among tumor ctDNA from mice with bigger tumors. Higher ctDNA fragmentation was also observed in plasma samples from three metastatic CRC patients in comparison to healthy individuals. Our data confirm the predominance of mononucleosome-derived fragments in plasma from xenografted animals and, as a consequence, of apoptosis as a source of ctDNA, in particular for tumor-derived ctDNA. Altogether, our results suggest that ctDNA features vary during CRC tumor development and our experimental system might be a useful tool to follow such variations

Intrapopulation Variability Shaping Isotope Discrimination and Turnover: Experimental Evidence in Arctic Foxes

Tissue-specific stable isotope signatures can provide insights into the trophic ecology of consumers and their roles in food webs. Two parameters are central for making valid inferences based on stable isotopes, isotopic discrimination (difference in isotopic ratio between consumer and its diet) and turnover time (renewal process of molecules in a given tissue usually measured when half of the tissue composition has changed). We investigated simultaneously the effects of age, sex, and diet types on the variation of discrimination and half-life in nitrogen and carbon stable isotopes (δ15N and δ13C, respectively) in five tissues (blood cells, plasma, muscle, liver, nail, and hair) of a top predator, the arctic fox Vulpes lagopus. We fed 40 farmed foxes (equal numbers of adults and yearlings of both sexes) with diet capturing the range of resources used by their wild counterparts. We found that, for a single species, six tissues, and three diet types, the range of discrimination values can be almost as large as what is known at the scale of the whole mammalian or avian class. Discrimination varied depending on sex, age, tissue, and diet types, ranging from 0.3‰ to 5.3‰ (mean = 2.6‰) for δ15N and from 0.2‰ to 2.9‰ (mean = 0.9‰) for δ13C. We also found an impact of population structure on δ15N half-life in blood cells. Varying across individuals, δ15N half-life in plasma (6 to 10 days) was also shorter than for δ13C (14 to 22 days), though δ15N and δ13C half-lives are usually considered as equal. Overall, our multi-factorial experiment revealed that at least six levels of isotopic variations could co-occur in the same population. Our experimental analysis provides a framework for quantifying multiple sources of variation in isotopic discrimination and half-life that needs to be taken into account when designing and analysing ecological field studies

Myeloid Heme Oxygenase-1 Haploinsufficiency Reduces High Fat Diet-Induced Insulin Resistance by Affecting Adipose Macrophage Infiltration in Mice

Increased adipose tissue macrophages contribute to obesity-induced metabolic syndrome. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with potent anti-inflammatory and proangiogenic activities in macrophages. However, the role of macrophage HO-1 on obesity-induced adipose inflammation and metabolic syndrome remains unclear. Here we show that high-fat diet (HFD) feeding in C57BL/6J mice induced HO-1 expression in the visceral adipose tissue, particularly the stromal vascular fraction. When the irradiated C57BL/6J mice reconstituted with wild-type or HO-1+/− bone marrow were fed with HFD for over 24 weeks, the HO-1+/− chimeras were protected from HFD-induced insulin resistance and this was associated with reduced adipose macrophage infiltration and angiogenesis, suggesting that HO-1 affects myeloid cell migration toward adipose tissue during obesity. In vivo and in vitro migration assays revealed that HO-1+/− macrophages exhibited an impaired migration response. Chemoattractant-induced phosphorylation of p38 and focal adhesion kinase (FAK) declined faster in HO-1+/− macrophages. Further experiments demonstrated that carbon monoxide and bilirubin, the byproducts derived from heme degradation by HO-1, enhanced macrophage migration by increasing phosphorylation of p38 and FAK, respectively. These data disclose a novel role of hematopoietic cell HO-1 in promoting adipose macrophage infiltration and the development of insulin resistance during obesity

MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

This article shows a novel function for the MAP1B protein, related to the control of actin dynamics through interaction with Tiam1