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Li E.,California Institute of Technology | Materna S.C.,Mission Research | Davidson E.H.,California Institute of Technology
Developmental Biology | Year: 2013

The sea urchin oral ectoderm gene regulatory network (GRN) model has increased in complexity as additional genes are added to it, revealing its multiple spatial regulatory state domains. The formation of the oral ectoderm begins with an oral-aboral redox gradient, which is interpreted by the cis-regulatory system of the nodal gene to cause its expression on the oral side of the embryo. Nodal signaling drives cohorts of regulatory genes within the oral ectoderm and its derived subdomains. Activation of these genes occurs sequentially, spanning the entire blastula stage. During this process the stomodeal subdomain emerges inside of the oral ectoderm, and bilateral subdomains defining the lateral portions of the future ciliary band emerge adjacent to the central oral ectoderm. Here we examine two regulatory genes encoding repressors, sip1 and ets4, which selectively prevent transcription of oral ectoderm genes until their expression is cleared from the oral ectoderm as an indirect consequence of Nodal signaling. We show that the timing of transcriptional de-repression of sip1 and ets4 targets which occurs upon their clearance explains the dynamics of oral ectoderm gene expression. In addition two other repressors, the direct Nodal target not, and the feed forward Nodal target goosecoid, repress expression of regulatory genes in the central animal oral ectoderm thereby confining their expression to the lateral domains of the animal ectoderm. These results have permitted construction of an enhanced animal ectoderm GRN model highlighting the repressive interactions providing precise temporal and spatial control of regulatory gene expression. © 2013 Elsevier Inc.

Materna S.C.,California Institute of Technology | Materna S.C.,Mission Research | Ransick A.,California Institute of Technology | Li E.,California Institute of Technology | Davidson E.H.,California Institute of Technology
Developmental Biology | Year: 2013

Specification of the non-skeletogenic mesoderm (NSM) in sea urchin embryos depends on Delta signaling. Signal reception leads to expression of regulatory genes that later contribute to the aboral NSM regulatory state. In oral NSM, this is replaced by a distinct oral regulatory state in consequence of Nodal signaling. Through regulome wide analysis we identify the homeobox gene not as an immediate Nodal target. not expression in NSM causes extinction of the aboral regulatory state in the oral NSM, and expression of a new suite of regulatory genes. All NSM specific regulatory genes are henceforth expressed exclusively, in oral or aboral domains, presaging the mesodermal cell types that will emerge. We have analyzed the regulatory linkages within the aboral NSM gene regulatory network. A linchpin of this network is gataE which as we show is a direct Gcm target and part of a feedback loop locking down the aboral regulatory state. © 2013 Elsevier Inc.

Settipane R.A.,Brown University | Schwindt C.,Mission Research
American Journal of Rhinology and Allergy | Year: 2013

Allergic rhinitis affects 60 million of the U.S. population, 1.4 billion of the global population, and its prevalence appears to be increasing. The duration and severity of allergic rhinitis symptoms place a substantial burden on patient's quality of life, sleep, work productivity, and activity. The health impact of allergic rhinitis is compounded by associated complications and comorbidities including asthma, otitis media, sinusitis, and nasal polyps. Allergic rhinitis symptoms result from a complex, allergen-driven mucosal inflammatory process, modulated by immunoglobulin E (IgE), and caused by interplay between resident and infiltrating inflammatory cells and a number of vasoactive and proinflammatory mediators, including cytokines. This allergic response may be characterized as three phases: IgE sensitization, allergen challenge, and elicitation of symptoms. A thorough allergic history is the best tool for the diagnosis of allergic rhinitis, the establishment of which is achieved by correlating the patient's history and physical exam with an assessment for the presence of specific IgE antibodies to relevant aeroallergens determined by skin testing or by in vitro assay. Management of allergic rhinitis includes modifying environmental exposures, implementing pharmacotherapy, and, in select cases, administering allergen-specific immunotherapy. Intranasal therapeutic options include antihistamines, anticholinergic agents, corticosteroids (aqueous or aerosol), mast cell stabilizers, saline, and brief courses of decongestants. Selection of pharmacotherapy is based on the severity and chronicity of symptoms with the most effective medications being intranasal corticosteroids and intranasal antihistamines, which can be used in combination (separately or in fixed dose) for more difficult to control allergic rhinitis. Copyright © 2013, OceanSide Publications, Inc.

Atopic dermatitis (AD) is an inflammatory skin disease commonly affecting children and managed by pediatricians, primary care physicians, allergists, and dermatologists alike. For many years, the only available topical pharmacological treatment was topical corticosteroids. This changed in 2000-2001, when topical formulations of two calcineurin inhibitors (tacrolimus and pimecrolimus) were approved for short-term or chronic intermittent treatment of AD in patients ≥2 years of age, in whom other treatments have been ineffective or contraindicated. These topical calcineurin inhibitors (TCIs) quickly became a popular treatment option due at least in part to concerns over adverse events associated with prolonged topical corticosteroid use, especially in children. However, based on theoretical concerns about a possible risk of lymphoma associated with TCI use, a Boxed Warning was placed on both products in 2006. Since then, despite an extensive body of evidence, no causal relationship has been demonstrated between TCI use and an increased risk of lymphoma; however, the US FDA has concluded that a link cannot be ruled out. In fact, based on post-marketing surveillance of spontaneous, literature, and solicited reports, we report here that the lymphoma incidence in the topical pimecrolimus-exposed population is up to approximately 54-fold less than that seen in the general US population. This review summarizes the mechanism of action of TCIs, the factors that prompted the Boxed Warning, and recent TCI safety and efficacy data. Based on these data, both topical corticosteroids and TCIs should have defined roles in AD management, with TCIs favored for sensitive skin areas (e.g., face) and instances where topical corticosteroids have proven ineffective, thereby minimizing the risk of adverse effects with both drug classes. © 2013 The Author(s).

Domenech C.,Free University of Berlin | Wehr T.,Mission Research
IEEE Transactions on Geoscience and Remote Sensing | Year: 2011

The Earth Clouds, Aerosols, and Radiation Explorer (EarthCARE) mission responds to the need to improve the understanding of the interactions between cloud, aerosol, and radiation processes. The fundamental mission objective is to constrain retrievals of cloud and aerosol properties such that their impact on top-of-atmosphere (TOA) radiative fluxes can be determined with an accuracy of 10 W · m -2. However, TOA fluxes cannot be measured instantaneously from a satellite. For the EarthCARE mission, fluxes will be estimated from the observed solar and thermal radiances measured by the Broadband Radiometer (BBR). This paper describes an approach to obtain shortwave (SW) fluxes from BBR radiance measurements. The retrieval algorithms are developed relying on the angular distribution models (ADMs) employed by Clouds and the Earth's Radiant Energy System (CERES) instrument. The solar radiance-to-flux conversion for the BBR is performed by simulating the Terra CERES ADMs using a backpropagation artificial neural network (ANN) technique. The ANN performance is optimized by testing different architectures, namely, feedforward, cascade forward, and a customized-forward network. A large data set of CERES measurements used to resemble the forthcoming BBR acquisitions has been collected. The CERES BBR-like database is sorted by their surface type, sky conditions, and scene type and then stratified by four input variables (solar zenith angle and BBR SW radiances) to construct three different training data sets. Then, the neural networks are analyzed, and the adequate ADM classification scheme is selected. The results of the BBR ANN-based ADMs show SW flux retrievals compliant with the CERES flux estimates. © 2011 IEEE.

Raju M.S.,Mission Research
Indian journal of leprosy | Year: 2011

In order to understand nature of the medical and society related problems of leprosy cured individuals from various socio-cultural groups and develop proper system to address the current needs of leprosy cured, data have been collected from leprosy cured, employing qualitative methods such as FGDs, open ended interviews and participant observation and a quantitative survey method. The findings show that there has been not much change in the socio-cultural and economic situation of the leprosy cured especially the disabled ones, except a recognition in the health system that their anti-leprosy treatment is completed. In the present integrated health care system, disabled leprosy patients are also expected to seek their own health care by themselves along with general public, which is not happening because the leprosy cured are not yet perceived to be cured of leprosy by community as well as by themselves. Though some of the problems of leprosy cured seem to be poverty related, qualitative analysis shows, a vast gap between poverty problem of leprosy afflicted and non leprosy afflicted. Any special programme to bridge the gap between PHC and leprosy community is required and the new functionaries like ASHA in National Rural Health Mission (NRHM) and similar developments could be of vital use to make them cured in totality.

Rao P.S.,Mission Research
The Indian journal of medical research | Year: 2013

Disability-adjusted life years (DALYs) have been accepted as a useful method to estimate the burden of disease, and can be adapted to determine the number of productive years lost due to the disability. DALY has been reported for many studies but not for leprosy. Hence this study was carried out in three States of India. In view of the fact that in this study, productive working years are used, the term is modified as DAWLY. A representative random sample of 150 leprosy affected persons, 50 from each States of Uttar Pradesh, West Bengal and Chhattisgarh, was chosen, and data were collected on detailed work-life history, occupation, time when leprosy was discovered, reported and treatment started, break of job/loss of income due to leprosy. The loss of wages and durations were used to compute the life-years lost due to leprosy, and summarized over the average total duration of 42 years of productive work-life from 18 to 60 years. The percentage losses were determined and differences tested for statistical significance. The overall mean (± SE) disability adjusted working life years was 28.6 (±0.67), a reduction of 13.4 yr from the ideal productive working life period of 42 yr. The youngest patients with disability had a reduction of 41.4 per cent, as compared to the oldest patients. There was a significant increase in loss based on year for those whose disability started earlier (P=0.0024). On an average, 30 per cent of the leprosy affected person's work life is lost due to disability.

Shenoy U.,Mission Research | Paul J.,Mission Research | Antony D.,Mission Research
Paediatric Anaesthesia | Year: 2014

A 3-year-old child was successfully resuscitated following bupivacaine cardiotoxicity with 20% intravenous lipid emulsion (ILE). Large volume of ILE was used targeting clinically adequate perfusion. Subsequently, there were features of ventilation/perfusion (V/P) mismatch. © 2013 John Wiley & Sons Ltd.

Morris J.K.,University of Kansas Medical Center | Burns J.M.,University of Kansas Medical Center | Burns J.M.,Mission Research
Current Neurology and Neuroscience Reports | Year: 2012

Accumulating evidence indicates a role for metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). It is widely reported that Type 2 diabetes (T2D) increases the risk of developing AD, and several postmortem analyses have found evidence of insulin resistance in the AD brain. Thus, insulin-based therapies have emerged as potential strategies to slow cognitive decline in AD. The main methods for targeting insulin to date have been intravenous insulin infusion, intranasal insulin administration, and use of insulin sensitizers. These methods have elicited variable results regarding improvement in cognitive function. This review will discuss the rationale for targeting insulin signaling to improve cognitive function in AD, the results of clinical studies that have targeted insulin signaling, and what these results mean for future studies of the role of insulin-based therapies for AD. © Springer Science+Business Media, LLC 2012.

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