Challenges and perspectives in computational deconvolution in genomics data

Deciphering cell type heterogeneity is crucial for systematically understanding tissue homeostasis and its dysregulation in diseases. Computational deconvolution is an efficient approach to estimate cell type abundances from a variety of omics data. Despite significant methodological progress in computational deconvolution in recent years, challenges are still outstanding. Here we enlist four significant challenges from availability of the reference data, generation of simulation data, limitations of computational methodologies, and benchmarking design and implementation. Finally, we make recommendations on reference data generation, new directions of computational methodologies and strategies to promote rigorous benchmarking

Rhodacyanine Derivative Selectively Targets Cancer Cells and Overcomes Tamoxifen Resistance

MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family

Proteomics in food: Quality, safety, microbes, and allergens

Food safety and quality and their associated risks pose a major concern worldwide regarding not only the relative economical losses but also the potential danger to consumer's health. Customer's confidence in the integrity of the food supply could be hampered by inappropriate food safety measures. A lack of measures and reliable assays to evaluate and maintain a good control of food characteristics may affect the food industry economy and shatter consumer confidence. It is imperative to create and to establish fast and reliable analytical methods that allow a good and rapid analysis of food products during the whole food chain. Proteomics can represent a powerful tool to address this issue, due to its proven excellent quantitative and qualitative drawbacks in protein analysis. This review illustrates the applications of proteomics in the past few years in food science focusing on food of animal origin with some brief hints on other types. Aim of this review is to highlight the importance of this science as a valuable tool to assess food quality and safety. Emphasis is also posed in food processing, allergies, and possible contaminants like bacteria, fungi, and other pathogens

Anthropogenic contributions to global carbonyl sulfide, carbon disulfide and organosulfides fluxes

Previous studies of the global sulfur cycle have focused almost exclusively on oxidized species and just a few sulfides. This focus is expanded here to include a wider range of reduced sulfur compounds. Inorganic sulfides tend to be bound into sediments, and sulfates are present both in sediments and the oceans. Sulfur can adopt polymeric forms that include S-S bonds. This review examines the global anthropogenic sources of reduced sulfur, updating emission inventories and widening the consideration of industrial sources. It estimates the anthropogenic fluxes of key sulfides to the atmosphere (units Gg S a-1) as: carbonyl sulfide (total 591: mainly from pulp and pigment 171, atmospheric oxidation of carbon disulfide 162, biofuel and coal combustion, 133, natural 898 Gg S a-1), carbon disulfide (total 746: rayon 395, pigment 205, pulp 78, natural 330 Gg S a-1), methanethiol (total 2119: pulp 1680, manure 330, rayon and wastewater 102, natural 6473 Gg S a-1), dimethyl sulfide (total 2197: pulp 1462, manure 660 and rayon 36, natural 31 657 Gg S a-1), dimethyl disulfide (total 1103: manure 660, pulp 273; natural 1081 Gg S a-1). The study compares the magnitude of the natural sources: marine, vegetation and soils, volcanoes and rain water with the key anthropogenic sources: paper industry, rayon-cellulose manufacture, agriculture and pigment production. Industrial sources could be reduced by better pollution control, so their impact may lessen over time. Anthropogenic emissions dominate the global budget of carbon disulfide, and some aromatic compounds such as thiophene, with emissions of methanethiol and dimethyl disufide also relatively important. Furthermore, industries related to coal and bitumen are key sources of multi-ringed thiophenes, while food production and various wastes may account for the release of significant amounts of dimethyl disulfide and dimethyl trisulfide

Stratospheric aerosol - Observations, processes, and impact on climate

Interest in stratospheric aerosol and its role in climate have increased over the last decade due to the observed increase in stratospheric aerosol since 2000 and the potential for changes in the sulfur cycle induced by climate change. This review provides an overview about the advances in stratospheric aerosol research since the last comprehensive assessment of stratospheric aerosol was published in 2006. A crucial development since 2006 is the substantial improvement in the agreement between in situ and space-based inferences of stratospheric aerosol properties during volcanically quiescent periods. Furthermore, new measurement systems and techniques, both in situ and space based, have been developed for measuring physical aerosol properties with greater accuracy and for characterizing aerosol composition. However, these changes induce challenges to constructing a long-term stratospheric aerosol climatology. Currently, changes in stratospheric aerosol levels less than 20% cannot be confidently quantified. The volcanic signals tend to mask any nonvolcanically driven change, making them difficult to understand. While the role of carbonyl sulfide as a substantial and relatively constant source of stratospheric sulfur has been confirmed by new observations and model simulations, large uncertainties remain with respect to the contribution from anthropogenic sulfur dioxide emissions. New evidence has been provided that stratospheric aerosol can also contain small amounts of nonsulfate matter such as black carbon and organics. Chemistry-climate models have substantially increased in quantity and sophistication. In many models the implementation of stratospheric aerosol processes is coupled to radiation and/or stratospheric chemistry modules to account for relevant feedback processes

The effect of Z-group modification on the RAFT polymerization of N-vinylpyrrolidone controlled by "switchable" N-pyridyl-functional dithiocarbamates

This is an accepted manuscript of an article published by Royal Society of Chemistry in the Polymer Chemistry on 24/08/2015, available online: https://doi.org/10.1039/C5PY01021G The accepted version of the publication may differ from the final published version.The ability of a RAFT agent to control the polymerization of a monomer is dictated by the structures of both the monomer and the RAFT agent. In this paper, the polymerization of N-vinylpyrrolidone was examined with a series of cyanomethyl N-aryl-N-pyridyldithiocarbamates [(4-R′Ph)N(py)C(S)SCH2CN] varying in the substituent (R′) at the 4-position on the phenyl ring. The polymerization of N-vinylpyrrolidone was best controlled when R′ was methoxy; one of the least active RAFT agents in the series. The preservation of RAFT agent functionality was demonstrated by chain extension experiments with further N-vinylpyrrolidone. Again best control again was found for the RAFT agent with R′ = MeOPh. The utility of this RAFT agent was also proved with the preparation of poly(N-isopropylacrylamide)-block-poly(N-vinylpyrrolidone).The authors gratefully acknowledge the Australian Government for award of an Australian Postgraduate Award to S.J.S., the CSIRO Manufacturing Flagship and the School of Science and Technology at the University of New England for project funding.Published versio

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass