Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay

Although delayed puberty is relatively common and often familial, its molecular and pathophysiologic basis is poorly understood. In contrast, the molecular mechanisms underlying some forms of hypogonadotropic hypogonadism (HH) are clearer, following the description of mutations in the genes KAL, GNRHR, and PROP1. Mutations in another gene, DAX1 (AHC), cause X-linked adrenal hypoplasia congenita and HH. Affected boys usually present with primary adrenal failure in infancy or childhood and HH at the expected time of puberty.DAX1 mutations have also been reported to occur with a wider spectrum of clinical presentations. These cases include female carriers of DAX1 mutations with marked pubertal delay and a male with incomplete BH and mild adrenal insufficiency in adulthood. Given this emerging phenotypic spectrum of clinical presentation in men and women with DAX1 mutations, we hypothesized that DAX1 might be a candidate gene for mutation in patients with idiopathic sporadic or familial HH or constitutional delay of puberty. Direct sequencing of DAX1 was performed in 106 patients, including 85 (80 men and 5 women) with sporadic HH or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified (T114C, G498A). This study suggests that mutations in DAX1 are unlikely to be a common cause of HH or pubertal delay in the absence of a concomitant history of adrenal insufficiency

Towards a Context-Aware Knowledge Model for Smart Service Systems

The advancement of the Internet of things, big data, and mobile computing leads to the need for smart services that enable the context awareness and the adaptability to their changing contexts. Today, designing a smart service system is a complex task due to the lack of an adequate model support in awareness and pervasive environment. In this paper, we present a context-aware knowledge model for smart service systems that organizes the domain and context-aware knowledge into knowledge components based on the three levels of services: Services, Service system and Network of service systems. The context-aware knowledge model for smart service systems integrates all the information and knowledge related to smart services, knowledge components and context awareness that can play a key role for any framework, infrastructure, or applications deploying smart services. To demonstrate the approach, a case study about a chatbot as a smart service for customer support is presented

6.25 Gb/s POF link using GaN μLED arrays and optically generated pulse amplitude modulation

Optically-generated PAM schemes using μLED arrays are implemented for high-speed POF links for the first time. 6.25Gb/s PAM-16 transmission is demonstrated using 4 μLEDs, exhibiting 3.8dB greater power-margin than a link with a single μLED.This work is supported by the UK Engineering and Physical Sciences Research Council (EPSRC) via the Ultra Parallel Visible Light Communication (UP-VLC) Project.This is the accepted manuscript of a paper published in CLEO: 2015 (X. Li, N. Bamiedakis, J. Wei, J. Mckendry, E. Xie, R. Ferreira, E. Gu, M. Dawson, R. V. Penty, and I. H. White, "6.25 Gb/s POF Link Using GaN μLED Arrays and Optically Generated Pulse Amplitude Modulation," in CLEO: 2015, OSA Technical Digest (online) (Optical Society of America, 2015), paper STu4F.7.). The final version is available at http://dx.doi.org/10.1364/CLEO_SI.2015.STu4F.7 © 2015 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibited

The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome

BACKGROUND: The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). METHODS: We measured prospectively tumour necrosis factor alpha (TNF-α), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). RESULTS: All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 – P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 – P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-α were negatively correlated to PaO(2)/FiO(2) (all P < 0.05). CONCLUSIONS: The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome

A view to kill

Genome and proteome data from Hydra magnipapillata have opened the way for the molecular analysis of an ancient nervous system, which includes stinging cells, an unusual neurosensory and neurosecretory cell type. They hold some surprises for the mechanisms and evolution of sensory transduction that could not have been anticipated from what has been learned from flies and vertebrates. Research in BMC Biology now implicates the ancient opsin-mediated transduction pathway in the neuronal control of stinging cell discharge

Integration of airborne and ground observations of nitryl chloride in the Seoul metropolitan area and the implications on regional oxidation capacity during KORUS-AQ 2016

Nitryl chloride (ClNO2) is a radical reservoir species that releases chlorine radicals upon photolysis. An integrated analysis of the impact of ClNO2 on regional photochemistry in the Seoul metropolitan area (SMA) during the Korea-United States Air Quality Study (KORUS-AQ) 2016 field campaign is presented. Comprehensive multiplatform observations were conducted aboard the NASA DC-8 and at two ground sites (Olympic Park, OP; Taehwa Research Forest, TRF), representing an urbanized area and a forested suburban region, respectively. Positive correlations between daytime Cl2 and ClNO2 were observed at both sites, the slope of which was dependent on O3 levels. The possible mechanisms are explored through box model simulations constrained with observations. The overall diurnal variations in ClNO2 at both sites appeared similar but the nighttime variations were systematically different. For about half of the observation days at the OP site the level of ClNO2 increased at sunset but rapidly decreased at around midnight. On the other hand, high levels were observed throughout the night at the TRF site. Significant levels of ClNO2 were observed at both sites for 4-5 h after sunrise. Airborne observations, box model calculations, and back-trajectory analysis consistently show that these high levels of ClNO2 in the morning are likely from vertical or horizontal transport of air masses from the west. Box model results show that chlorine-radical-initiated chemistry can impact the regional photochemistry by elevating net chemical production rates of ozone by 25% in the morning

High speed plastic optical fiber data links using LEDs

Manuscript originally submitted to the repository as for publication by IEEE in the papers of the International Conference On Communication Problem-Solving (ICCP2014). However, it does not appear among the published papers for this conference, and no reference has been found to it being published elsewhere.Plastic optical fiber (POF) data links have been widely viewed as a cost- and energy- effective solutions for short-reach Gigabit data communications such as in-home and automotive networks. POF also has excellent compatibility with low-cost light-emitting-diodes (LEDs). In this paper, we demonstrate a 4 Gb/s single micro-LED (μLED) PAM-16 link and a record 4.7 Gb/s multiple μLEDs PAM-8 link by 1) use of avalanche photodiodes (APD) in combination with high order modulation formats; and 2) illumination of multiple μLEDs. Both digital implementation based on FPGA and analogue implementation are considered for real-time transmitters

The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome

BACKGROUND: The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). METHODS: We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). RESULTS: An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively). CONCLUSIONS: BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS

Asymmetric Origin for Gravitino Relic Density in the Hybrid Gravity-Gauge Mediated Supersymmetry Breaking

We propose the hybrid gravity-gauge mediated supersymmetry breaking where the gravitino mass is about several GeV. The strong constraints on supersymmetry viable parameter space from the CMS and ATLAS experiments at the LHC can be relaxed due to the heavy colored supersymmetric particles, and it is consistent with null results in the dark matter (DM) direct search experiments such as XENON100. In particular, the possible maximal flavor and CP violations from the relatively small gravity mediation may naturally account for the recent LHCb anomaly. In addition, because the gravitino mass is around the asymmetric DM mass, we propose the asymmetric origin of the gravitino relic density and solve the cosmological coincident problem on the DM and baryon densities \Omega_{\rm DM}:\Omega_{B}\approx 5:1. The gravitino relic density arises from asymmetric metastable particle (AMP) late decay. However, we show that there is no AMP candidate in the minimal supersymmetric Standard Model (SM) due to the robust gaugino/Higgsino mediated wash-out effects. Interestingly, AMP can be realized in the well motivated supersymmetric SMs with vector-like particles or continuous U(1)_R symmetry. Especially, the lightest CP-even Higgs boson mass can be lifted in the supersymmetric SMs with vector-like particles.Comment: RevTex4, 21 pages, 1 figure, minor corrections, JHEP versio

Asymmetric Dark Matter from Leptogenesis

We present a new realization of asymmetric dark matter in which the dark matter and lepton asymmetries are generated simultaneously through two-sector leptogenesis. The right-handed neutrinos couple both to the Standard Model and to a hidden sector where the dark matter resides. This framework explains the lepton asymmetry, dark matter abundance and neutrino masses all at once. In contrast to previous realizations of asymmetric dark matter, the model allows for a wide range of dark matter masses, from keV to 10 TeV. In particular, very light dark matter can be accommodated without violating experimental constraints. We discuss several variants of our model that highlight interesting phenomenological possibilities. In one, late decays repopulate the symmetric dark matter component, providing a new mechanism for generating a large annihilation rate at the present epoch and allowing for mixed warm/cold dark matter. In a second scenario, dark matter mixes with the active neutrinos, thus presenting a distinct method to populate sterile neutrino dark matter through leptogenesis. At late times, oscillations and dark matter decays lead to interesting indirect detection signals.Comment: 32 pages + appendix, references added, minor change