An in silico model to demonstrate the effects of Maspin on cancer cell dynamics

Most cancer treatments efficacy depends on tumor metastasis suppression, where tumor suppressor genes play an important role. Maspin (Mammary Serine Protease Inhibitor), an non-inhibitory serpin has been reported as a potential tumor suppressor to influence cell migration, adhesion, proliferation and apoptosis in in vitro and in vivo experiments in last two decades. Lack of computational investigations hinders its ability to go through clinical trials. Previously, we reported first computational model for maspin effects on tumor growth using artificial neural network and cellular automata paradigm with in vitro data support. This paper extends the previous in silico model by encompassing how maspin influences cell migration and the cell–extracellular matrix interaction in subcellular level. A feedforward neural network was used to define each cell behavior (proliferation, quiescence, apoptosis) which followed a cell-cycle algorithm to show the microenvironment impacts over tumor growth. Furthermore, the model concentrates how the in silico experiments results can further confirm the fact that maspin reduces cell migration using specific in vitro data verification method. The data collected from in vitro and in silico experiments formulates an unsupervised learning problem which can be solved by using different clustering algorithms. A density based clustering technique was developed to measure the similarity between two datasets based on the number of links between instances. Our proposed clustering algorithm first finds the nearest neighbors of each instance, and then redefines the similarity between pairs of instances in terms of how many nearest neighbors share the two instances. The number of links between two instances is defined as the number of common neighbors they have. The results showed significant resemblances with in vitro experimental data. The results also offer a new insight into the dynamics of maspin and establish as a metastasis suppressor gene for further molecular research

Theory and laboratory astrophysics

Science opportunities in the 1990's are discussed. Topics covered include the large scale structure of the universe, galaxies, stars, star formation and the interstellar medium, high energy astrophysics, and the solar system. Laboratory astrophysics in the 1990's is briefly surveyed, covering such topics as molecular, atomic, optical, nuclear and optical physics. Funding recommendations are given for the National Science Foundation, NASA, and the Department of Energy. Recommendations for laboratory astrophysics research are given

Effects of Noninhibitory Serpin Maspin on the Actin Cytoskeleton: A Quantitative Image Modeling Approach

Recent developments in quantitative image analysis allow us to interrogate confocal microscopy images to answer biological questions. Clumped and layered cell nuclei and cytoplasm in confocal images challenges the ability to identify subcellular compartments. To date, there is no perfect image analysis method to identify cytoskeletal changes in confocal images. Here, we present a multidisciplinary study where an image analysis model was developed to allow quantitative measurements of changes in the cytoskeleton of cells with different maspin exposure. Maspin, a noninhibitory serpin influences cell migration, adhesion, invasion, proliferation, and apoptosis in ways that are consistent with its identification as a tumor metastasis suppressor. Using different cell types, we tested the hypothesis that reduction in cell migration by maspin would be reflected in the architecture of the actin cytoskeleton. A hybrid marker-controlled watershed segmentation technique was used to segment the nuclei, cytoplasm, and ruffling regions before measuring cytoskeletal changes. This was informed by immunohistochemical staining of cells transfected stably or transiently with maspin proteins, or with added bioactive peptides or protein. Image analysis results showed that the effects of maspin were mirrored by effects on cell architecture, in a way that could be described quantitatively

The ACS Nearby Galaxy Survey Treasury. X. Quantifying the Star Cluster Formation Efficiency of Nearby Dwarf Galaxies

We study the relationship between the field star formation and cluster formation properties in a large sample of nearby dwarf galaxies. We use optical data from the Hubble Space Telescope and from ground-based telescopes to derive the ages and masses of the young (t_age < 100Myr) cluster sample. Our data provides the first constraints on two proposed relationships between the star formation rate of galaxies and the properties of their cluster systems in the low star formation rate regime. The data show broad agreement with these relationships, but significant galaxy-to-galaxy scatter exists. In part, this scatter can be accounted for by simulating the small number of clusters detected from stochastically sampling the cluster mass function. However, this stochasticity does not fully account for the observed scatter in our data suggesting there may be true variations in the fraction of stars formed in clusters in dwarf galaxies. Comparison of the cluster formation and the brightest cluster in our sample galaxies also provide constraints on cluster destruction models.Comment: 16 pages, 9 figures, Accepted to Ap

Versatile Graded-Index Multi-Mode Fiber for High Capacity Single-and Multi-Mode Optical Home Network

International audienceA graded-index multi-mode fiber has been optimized to sustain a single excited mode when coupled with a standard single-mode fiber at 1310/1550nm while offering large effective modal bandwidth at 850nm under VCSEL excitations. Modeling and experimental results are presented

A New Era in Extragalactic Background Light Measurements: The Cosmic History of Accretion, Nucleosynthesis and Reionization

(Brief Summary) What is the total radiative content of the Universe since the epoch of recombination? The extragalactic background light (EBL) spectrum captures the redshifted energy released from the first stellar objects, protogalaxies, and galaxies throughout cosmic history. Yet, we have not determined the brightness of the extragalactic sky from UV/optical to far-infrared wavelengths with sufficient accuracy to establish the radiative content of the Universe to better than an order of magnitude. Among many science topics, an accurate measurement of the EBL spectrum from optical to far-IR wavelengths, will address: What is the total energy released by stellar nucleosynthesis over cosmic history? Was significant energy released by non-stellar processes? Is there a diffuse component to the EBL anywhere from optical to sub-millimeter? When did first stars appear and how luminous was the reionization epoch? Absolute optical to mid-IR EBL spectrum to an astrophysically interesting accuracy can be established by wide field imagingat a distance of 5 AU or above the ecliptic plane where the zodiacal foreground is reduced by more than two orders of magnitude.Comment: 7 pages; Science White Paper for the US Astro 2010-2020 Decadal Survey. If interested in further community-wide efforts on this topic please contact the first autho

A systematic review of interventions on body image and disordered eating outcomes among women in midlife

Objective: Body dissatisfaction and disordered eating are widely recognised as issues that warrant attention among women in midlife, particularly the development and delivery of effective interventions. This paper systematically reviews existing research on interventions among midlife women on body image and disordered eating outcomes, in order to inform intervention delivery and provide strategic directions for future research.Method: Fourteen electronic databases were searched for articles published between 1992-2015 that evaluated interventions with non-clinical samples of women (M age 35-55 years) in controlled trials with at least one body image measure. Data were extracted and evaluated, and the methodological quality of studies was assessed using the Cochrane Collaboration tool for assessing risk of bias.Results: From 7,475 records identified, 9 articles evaluating 11 interventions met the inclusion criteria. Seven interventions significantly improved body image at post-test (ds = 0.19-2.22), with significant improvements on disordered eating achieved by two of these interventions (ds = 0.90-1.72). Sustained improvements were achieved by three interventions that employed a multi-session, therapeutically based, group intervention format; two with sustained body image and disordered eating improvements, and one with sustained body image improvements only (ds = 0.55-1.21; 2 weeks-6 months). Methodological quality varied between studies. Discussion: To date, three interventions have demonstrated sustained improvements and are indicated for practitioners aiming to improve body image and disordered eating among women in midlife. Replication and more rigorous randomised controlled trials are required to enhance the methodological quality of intervention studies in this field

Cytoplasmic CUG RNA Foci Are Insufficient to Elicit Key DM1 Features

The genetic basis of myotonic dystrophy type I (DM1) is the expansion of a CTG tract located in the 3′ untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG)400 repeat tract was positioned 3′ of the termination codon and 5′ of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA aggregates is an important variable that influences toxicity and support the hypothesis that small molecules that increase the rate of transport of the mutant DMPK RNA from the nucleus into the cytoplasm may significantly improve DM1 pathology