Novel peptides of therapeutic promise from Indian conidae

Highly structured small peptides are the major toxic constituents of the venom of cone snails, a family of widely distributed predatory marine molluscs. These animals use the venom for rapid prey immobilization. The peptide components in the venom target a wide variety of membrane-bound ion channels and receptors. Many have been found to be highly selective for a diverse range of mammalian ion channels and receptors associated with pain-signaling pathways. Their small size, structural stability, and target specificity make them attractive pharmacologic agents. A select number of laboratories mainly from the United States, Europe, Australia, Israel, and China have been engaged in intense drug discovery programs based on peptides from a few snail species. Coastal India has an estimated 20-30% of the known cone species; however, few serious studies have been reported so far. We have begun a comprehensive program for the identification and characterization of peptides from cone snails found in Indian Coastal waters. This presentation reviews our progress over the last 2 years. As expected from the evolutionary history of these venom components, our search has yielded novel peptides of therapeutic promise from the new species that we have studied

Saturation in cascaded optical amplifier free-space optical communication systems

The performance of a free-space optical (FSO) communication system in a turbulent atmosphere employing an optical amplifier (OA) cascade to extend reach is investigated. Analysis of both single and cascaded OA FSO communication links is given and the implications of using both adaptive (to channel state) and non-adaptive decision threshold schemes are analysed. The benefits of amplifier saturation, for example in the form of effective scintillation reduction when a non-adaptive decision threshold scheme is utilised at the receiver for different atmospheric turbulence regimes, are presented. Monte Carlo simulation techniques are used to model the probability distributions of the optical signal power, noise and the average bit error rate due to scintillation for the cascade. The performance of an adaptive decision threshold is superior to a non-adaptive decision threshold for both saturated and fixed gain preamplified receivers and the ability of a saturated gain OA to suppress scintillation is only meaningful for system performance when a non-adaptive decision threshold is used at the receiver. An OA cascade can be successfully used to extend reach in FSO communication systems and specific system implementations are presented. The optimal cascade scheme with a non-adaptive receiver would use frequent low gain saturated amplification

Presenting signs and patient co-variables in Gaucher disease : outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative

© 2018 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.Background: Gaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities. Aim: The Gaucher Earlier Diagnosis Consensus (GED-C) initiative aimed to identify signs and co-variables considered most indicative of early type 1 and type 3 GD, to help non-specialists identify ‘at-risk’ patients who may benefit from diagnostic testing. Methods: An anonymous, three-round Delphi consensus process was deployed among a global panel of 22 specialists in GD (median experience 17.5 years, collectively managing almost 3000 patients). The rounds entailed data gathering, then importance ranking and establishment of consensus, using 5-point Likert scales and scoring thresholds defined a priori. Results: For type 1 disease, seven major signs (splenomegaly, thrombocytopenia, bone-related manifestations, anaemia, hyperferritinaemia, hepatomegaly and gammopathy) and two major co-variables (family history of GD and Ashkenazi-Jewish ancestry) were identified. For type 3 disease, nine major signs (splenomegaly, oculomotor disturbances, thrombocytopenia, epilepsy, anaemia, hepatomegaly, bone pain, motor disturbances and kyphosis) and one major co-variable (family history of GD) were identified. Lack of disease awareness, overlooking mild early signs and failure to consider GD as a diagnostic differential were considered major barriers to early diagnosis. Conclusion: The signs and co-variables identified in the GED-C initiative as potentially indicative of early GD will help to guide non-specialists and raise their index of suspicion in identifying patients potentially suitable for diagnostic testing for GD.Peer reviewedFinal Published versio

Schemes of transmission of classical information via quantum channels with many senders: discrete and continuous variables cases

Superadditivity effects in the classical capacity of discrete multi-access channels (MACs) and continuous variable (CV) Gaussian MACs are analysed. New examples of the manifestation of superadditivity in the discrete case are provided including, in particular, a channel which is fully symmetric with respect to all senders. Furthermore, we consider a class of channels for which {\it input entanglement across more than two copies of the channels is necessary} to saturate the asymptotic rate of transmission from one of the senders to the receiver. The 5-input entanglement of Shor error correction codewords surpass the capacity attainable by using arbitrary two-input entanglement for these channels. In the CV case, we consider the properties of the two channels (a beam-splitter channel and a "non-demolition" XP gate channel) analyzed in [Czekaj {\it et al.}, Phys. Rev. A {\bf 82}, 020302 (R) (2010)] in greater detail and also consider the sensitivity of capacity superadditivity effects to thermal noise. We observe that the estimates of amount of two-mode squeezing required to achieve capacity superadditivity are more optimistic than previously reported.Comment: 19 pages, 11 figure

A genome-wide resource for the analysis of protein localisation in Drosophila

The Drosophila genome contains >13000 protein-coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here, we present a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins, we created transgenic lines, and for a total of 207 lines, we assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we visualised many proteins at endogenous expression levels and found a large fraction of them localising to subcellular compartments. By applying genetic complementation tests, we estimate that about two-thirds of the tagged proteins are functional. Moreover, these tagged proteins enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will boost systematic analysis of protein expression and localisation in various cellular and developmental contexts

Uncovering Blind Spots in Urban Carbon Management: The Role of Consumption-Based Carbon Accounting in Bristol, UK

The rapid urbanisation of the twentieth century, along with the spread of high-consumption urban lifestyles, has led to cities becoming the dominant drivers of global anthropogenic greenhouse gas emissions. Reducing these impacts is crucial, but production-based frameworks of carbon measurement and mitigation—which encompass only a limited part of cities’ carbon footprints—are much more developed and widely applied than consumption-based approaches that consider the embedded carbon effectively imported into a city. Frequently, therefore, cities are left blind to the importance of their wider consumption-related climate impacts, while at the same time left lacking effective tools to reduce them. To explore the relevance of these issues, we implement methodologies for assessing production- and consumption-based emissions at the city-level and estimate the associated emissions trajectories for Bristol, a major UK city, from 2000 to 2035. We develop mitigation scenarios targeted at reducing the former, considering potential energy, carbon and financial savings in each case. We then compare these mitigation potentials with local government ambitions and Bristol’s consumption-based emissions trajectory. Our results suggest that the city’s consumption-based emissions are three times the production-based emissions, largely due to the impacts of imported food and drink. We find that low-carbon investments of circa £3 billion could reduce production-based emissions by 25% in 2035. However, we also find that this represents <10% of Bristol’s forecast consumption-based emissions for 2035 and is approximately equal to the mitigation achievable by eliminating the city’s current levels of food waste. Such observations suggest that incorporating consumption-based emission statistics into cities’ accounting and decision-making processes could uncover largely unrecognised opportunities for mitigation that are likely to be essential for achieving deep decarbonisation

Unequal household carbon footprints in China

Households’ carbon footprints are unequally distributed among the rich and poor due to differences in the scale and patterns of consumption. We present distributional focused carbon footprints for Chinese households and use a carbon-footprint-Gini coefficient to quantify inequalities. We find that in 2012 the urban very rich, comprising 5% of population, induced 19% of the total carbon footprint from household consumption in China, with 6.4 tCO2/cap. The average Chinese household footprint remains comparatively low (1.7 tCO2/cap), while those of the rural population and urban poor, comprising 58% of population, are 0.5–1.6 tCO2/cap. Between 2007 and 2012 the total footprint from households increased by 19%, with 75% of the increase due to growing consumption of the urban middle class and the rich. This suggests that a transformation of Chinese lifestyles away from the current trajectory of carbon-intensive consumption patterns requires policy interventions to improve living standards and encourage sustainable consumption