Iterative Reconstruction of Transcriptional Regulatory Networks: An Algorithmic Approach

The number of complete, publicly available genome sequences is now greater than 200, and this number is expected to rapidly grow in the near future as metagenomic and environmental sequencing efforts escalate and the cost of sequencing drops. In order to make use of this data for understanding particular organisms and for discerning general principles about how organisms function, it will be necessary to reconstruct their various biochemical reaction networks. Principal among these will be transcriptional regulatory networks. Given the physical and logical complexity of these networks, the various sources of (often noisy) data that can be utilized for their elucidation, the monetary costs involved, and the huge number of potential experiments (~10(12)) that can be performed, experiment design algorithms will be necessary for synthesizing the various computational and experimental data to maximize the efficiency of regulatory network reconstruction. This paper presents an algorithm for experimental design to systematically and efficiently reconstruct transcriptional regulatory networks. It is meant to be applied iteratively in conjunction with an experimental laboratory component. The algorithm is presented here in the context of reconstructing transcriptional regulation for metabolism in Escherichia coli, and, through a retrospective analysis with previously performed experiments, we show that the produced experiment designs conform to how a human would design experiments. The algorithm is able to utilize probability estimates based on a wide range of computational and experimental sources to suggest experiments with the highest potential of discovering the greatest amount of new regulatory knowledge

q-breathers in Discrete Nonlinear Schroedinger lattices

$q$-breathers are exact time-periodic solutions of extended nonlinear systems continued from the normal modes of the corresponding linearized system. They are localized in the space of normal modes. The existence of these solutions in a weakly anharmonic atomic chain explained essential features of the Fermi-Pasta-Ulam (FPU) paradox. We study $q$-breathers in one- two- and three-dimensional discrete nonlinear Sch\"{o}dinger (DNLS) lattices -- theoretical playgrounds for light propagation in nonlinear optical waveguide networks, and the dynamics of cold atoms in optical lattices. We prove the existence of these solutions for weak nonlinearity. We find that the localization of $q$-breathers is controlled by a single parameter which depends on the norm density, nonlinearity strength and seed wave vector. At a critical value of that parameter $q$-breathers delocalize via resonances, signaling a breakdown of the normal mode picture and a transition into strong mode-mode interaction regime. In particular this breakdown takes place at one of the edges of the normal mode spectrum, and in a singular way also in the center of that spectrum. A stability analysis of $q$-breathers supplements these findings. For three-dimensional lattices, we find $q$-breather vortices, which violate time reversal symmetry and generate a vortex ring flow of energy in normal mode space.Comment: 19 pages, 9 figure

Infecção congênita pelo citomegalovírus: ocorrência em duas populações de nível sócio-econômico diferentes em São Paulo, Brasil

In São Paulo, Brazil, between November 1980 and July 1982, 1614 newborns of middle socioeconomic background and 1156 newborns of low socioeconomic background were examined for the occurrence of congenital cytomegalovirus (CMV) infection by isolation of virus from urine samples or detection of specific anti-CMV IgM in umbilical cord serum tested by immunofluorescence. In the low socioeconomic population prevalence of CMV complement-fixing antibodies in mothers was 84.4%(151/179) and the incidence of congenital infection assessed by virus isolation 0.98% (5/508), as compared with 0.46% (3/648) in the group of newborns tested by detection of specific anti-CMV IgM in umbilical cord-serum. In middle socioeconomic level population prevalence of CMV complement-fixing antibodies in mothers was 66.5% (284/427) and the incidence of CMV congenital infection was 0.39% (2/518) in the group of newborns screened by virus isolation and 0.18% (2/1096) in the group tested by detection of specific anti-CMV IgM. In the present study none of the 12 congenitally infected newborns presented clinical apparent disease at birth.Entre novembro de 1980 e julho de 1982, 1614 recém-nascidos (RNs) de nivel sócio-econômico médio e 1156 RNs de baixo nível sócioeconômico foram examinados para verificar a ocorrência de infecção congênita pelo citomegalovírus (CMV), através de isolamento do vírus em amostras de urina ou detecção de anticorpos IgM específicos em amostras de sangue de cordão umbilical. Na população de baixo nível sócio econômico a prevalência de anticorpos fixadores do complemento (Ac Fc) anti-CMV nas mães foi de 84,4% (151/179) e a incidência de infecção congênita determinada por isolamento do vírus foi de 0,90% (5/508). No grupo de RNs em que o diagnóstico baseou-se apenas na detecção de Ac IgM CMV-específicos no sangue de cordão a incidência de infecção congênita foi de apenas 0,46% (3/648). Na população de nivel sócio-econômico médio a prevalência de Ac Fc anti-CMV nas mães foi de 66,5% (284/427) e a incidência de infecção congênita foi de 0,39% (2/518) no grupo de RNs testados por isolamento de vírus na urina e 0,18% (2/1090) no grupo testado por detecção de Ac IgM específicos. No presente estudo nenhum dos 12 RNs infectados congenitamente apresentou sinais ou sintomas de doença ao nascimento

Immiscible fluid displacement in porous media with spatially correlated particle sizes

Immiscible fluid displacement in porous media is fundamental for many environmental processes, including infiltration of water in soils, groundwater remediation, enhanced recovery of hydrocarbons and CO2 geosequestration. Microstructural heterogeneity, in particular of particle sizes, can significantly impact immiscible displacement. For instance, it may lead to unstable flow and preferential displacement patterns. We present a systematic, quantitative pore-scale study of the impact of spatial correlations in particle sizes on the drainage of a partially-wetting fluid. We perform pore-network simulations with varying flow rates and different degrees of spatial correlation, complemented with microfluidic experiments. Simulated and experimental displacement patterns show that spatial correlation leads to more preferential invasion, with reduced trapping of the defending fluid, especially at low flow rates. Numerically, we find that increasing the correlation length reduces the fluid-fluid interfacial area and the trapping of the defending fluid, and increases the invasion pattern asymmetry and selectivity. Our experiments, conducted for low capillary numbers, support these findings. Our results delineate the significant effect of spatial correlations on fluid displacement in porous media, of relevance to a wide range of natural and engineered processes

UV to near-IR observations of the DART-Dimorphos collision

The impact of the Double Asteroid Redirection Test (DART) spacecraft with Dimorphos allows us to study asteroid collision physics, including momentum transfer, the ejecta properties, and the visibility of such events in the Solar System. We report observations of the DART impact in the ultraviolet (UV), visible light, and near-infrared (IR) wavelengths. The observations support the existence of at least two separate components of the ejecta: a fast and a slow component. The fast-ejecta component is composed of a gaseous phase, moving at about 1.6 km/s with a mass of <10^4 kg. The fast ejecta is detected in the UV and visible light, but not in the near-IR $z$-band observations. Fitting a simplified optical thickness model to these observations allows us to constrain some of the properties of the fast ejecta, including its scattering efficiency and the opacity of the gas. The slow ejecta component is moving at typical velocities of up to about 10 m/s. It is composed of micrometer-size particles, that have a scattering efficiency, at the direction of the observer, of the order of 10^-3 and a total mass of about 10^6 kg. The larger particles in the slow ejecta, whose size is bound to be in the range between ~1 mm to ~1 m, likely have a scattering efficiency larger than that of the pre-impact Didymos system.Comment: Submitted to MNRA

Lines on projective varieties and applications

The first part of this note contains a review of basic properties of the variety of lines contained in an embedded projective variety and passing through a general point. In particular we provide a detailed proof that for varieties defined by quadratic equations the base locus of the projective second fundamental form at a general point coincides, as a scheme, with the variety of lines. The second part concerns the problem of extending embedded projective manifolds, using the geometry of the variety of lines. Some applications to the case of homogeneous manifolds are included.Comment: 15 pages. One example removed; one remark and some references added; typos correcte

The Large Array Survey Telescope -- System Overview and Performances

The Large Array Survey Telescope (LAST) is a wide-field visible-light telescope array designed to explore the variable and transient sky with a high cadence. LAST will be composed of 48, 28-cm f/2.2 telescopes (32 already installed) equipped with full-frame backside-illuminated cooled CMOS detectors. Each telescope provides a field of view (FoV) of 7.4 deg^2 with 1.25 arcsec/pix, while the system FoV is 355 deg^2 in 2.9 Gpix. The total collecting area of LAST, with 48 telescopes, is equivalent to a 1.9-m telescope. The cost-effectiveness of the system (i.e., probed volume of space per unit time per unit cost) is about an order of magnitude higher than most existing and under-construction sky surveys. The telescopes are mounted on 12 separate mounts, each carrying four telescopes. This provides significant flexibility in operating the system. The first LAST system is under construction in the Israeli Negev Desert, with 32 telescopes already deployed. We present the system overview and performances based on the system commissioning data. The Bp 5-sigma limiting magnitude of a single 28-cm telescope is about 19.6 (21.0), in 20 s (20x20 s). Astrometric two-axes precision (rms) at the bright-end is about 60 (30)\,mas in 20\,s (20x20 s), while absolute photometric calibration, relative to GAIA, provides ~10 millimag accuracy. Relative photometric precision, in a single 20 s (320 s) image, at the bright-end measured over a time scale of about 60 min is about 3 (1) millimag. We discuss the system science goals, data pipelines, and the observatory control system in companion publications.Comment: Submitted to PASP, 15p

Pasquale del Pezzo, Duke of Caianello, Neapolitan mathematician

This article is dedicated to a reconstruction of some events and achievements, both personal and scientific, in the life of the Neapolitan mathematician Pasquale del Pezzo, Duke of Caianello