Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

The Role of Thailand in the International Trade in CITES-Listed Live Reptiles and Amphibians

BACKGROUND: International wildlife trade is one of the leading threats to biodiversity conservation. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) is the most important initiative to monitor and regulate the international trade of wildlife but its credibility is dependent on the quality of the trade data. We report on the performance of CITES reporting by focussing on the commercial trade in non-native reptiles and amphibians into Thailand as to illustrate trends, species composition and numbers of wild-caught vs. captive-bred specimens. METHODOLOGY/PRINCIPAL FINDINGS: Based on data in the WCMC-CITES trade database, we establish that a total of 75,594 individuals of 169 species of reptiles and amphibians (including 27 globally threatened species) were imported into Thailand in 1990-2007. The majority of individuals (59,895, 79%) were listed as captive-bred and a smaller number (15,699, 21%) as wild-caught. In the 1990s small numbers of individuals of a few species were imported into Thailand, but in 2003 both volumes and species diversity increased rapidly. The proportion of captive-bred animals differed greatly between years (from 0 to >80%). Wild-caught individuals were mainly sourced from African countries, and captive-bred individuals from Asian countries (including from non-CITES Parties). There were significant discrepancies between exports and imports. Thailand reports the import of >10,000 individuals (51 species) originating from Kazakhstan, but Kazakhstan reports no exports of these species. Similar discrepancies, involving smaller numbers (>100 individuals of 9 species), can be seen in the import of reptiles into Thailand via Macao. CONCLUSION/SIGNIFICANCE: While there has been an increase in imports of amphibian and reptiles into Thailand, erratic patterns in proportions of captive-bred specimens and volumes suggests either capricious markets or errors in reporting. Large discrepancies with respect to origin point to misreporting or possible violations of the rules and intentions of CITES

Novel strategies lead to pre-elimination of malaria in previously high-risk areas in Suriname, South America

<p>Abstract</p> <p>Background</p> <p>Suriname was a high malaria risk country before the introduction of a new five-year malaria control program in 2005, the Medical Mission Malaria Programme (MM-MP). Malaria was endemic in the forested interior, where especially the stabile village communities were affected.</p> <p>Case description</p> <p>The interventions of the MM-MP included new strategies for prevention, vector control, case management, behavioral change communication (BCC)/information, education and communication (IEC), and strengthening of the health system (surveillance, monitoring and evaluation and epidemic detection system). After a slow first year with non-satisfying scores for the performance indicators, the MM-MP truly engaged in its intervention activities in 2006 and kept its performance up until the end of 2009. A total of 69,994 long-lasting insecticide-treated nets were distributed and more than 15,000 nets re-impregnated. In high-risk areas, this was complemented with residual spraying of insecticides. Over 10,000 people were screened with active case detection in outbreak and high-risk areas. Additional notification points were established and the national health system was strengthened.</p> <p>Discussion and evaluation</p> <p>In the current paper, the MM-MP is evaluated both on account of the targets established within the programme and on account of its impact on the malaria situation in Suriname. Malaria vector populations, monitored in sentinel sites, collapsed after 2006 and concurrently the number of national malaria cases decreased from 8,618 in 2005 to 1,509 in 2009. Malaria transmission risk shifted from the stabile village communities to the mobile gold mining communities, especially those along the French Guiana border.</p> <p>Conclusions</p> <p>The novel strategies for malaria control introduced in Suriname within the MM-MP have led to a significant decrease in the national malaria burden. The challenge is to further reduce malaria using the available strategies as appropriate in the affected areas and populations. Elimination of malaria in the country will require a thorough understanding of transmission dynamics and a dedicated investment in key effective interventions.</p

A retrospective and agenda for future research on Chinese outward foreign direct investment

Our original paper “The determinants of Chinese Outward Foreign Direct Investment” was the first theoretically based empirical analysis of the phenomenon. It utilised internalisation theory to show that Chinese state-owned firms reacted to home country market imperfections to surmount barriers to foreign entry arising from naivety and the lack of obvious ownership advantages, leveraging institutional factors including favourable policy stimuli. This special theory explained outward foreign direct investment (OFDI) but provided surprises. These included the apparent appetite for risk evinced by these early investors, causing us to conjecture that domestic market imperfections, particularly in the domestic capital market, might be responsible. The article stimulated a massive subsequent, largely successful, research effort on emerging country multinationals. In this Retrospective article we review some of the main strands of research that ensued, for the insight they offer for the theme of our commentary. Our theme is that theoretical development can only come through embracing yet more challenging, different, and new contexts, and we make suggestions for future research directions

DPRESS: Localizing estimates of predictive uncertainty

<p>Abstract</p> <p>Background</p> <p>The need to have a quantitative estimate of the uncertainty of prediction for QSAR models is steadily increasing, in part because such predictions are being widely distributed as tabulated values disconnected from the models used to generate them. Classical statistical theory assumes that the error in the population being modeled is independent and identically distributed (IID), but this is often not actually the case. Such inhomogeneous error (heteroskedasticity) can be addressed by providing an individualized estimate of predictive uncertainty for each particular new object <it>u</it>: the standard error of prediction <it>s</it>_ucan be estimated as the non-cross-validated error <it>s</it>_t*for the closest object <it>t</it>* in the training set adjusted for its separation <it>d </it>from <it>u </it>in the descriptor space relative to the size of the training set.</p> <p><display-formula><graphic file="1758-2946-1-11-i1.gif"/></display-formula></p> <p>The predictive uncertainty factor <it>γ</it>_t*is obtained by distributing the internal predictive error sum of squares across objects in the training set based on the distances between them, hence the acronym: <it>D</it>istributed <it>PR</it>edictive <it>E</it>rror <it>S</it>um of <it>S</it>quares (DPRESS). Note that <it>s</it>_t*and <it>γ</it>_t*are characteristic of each training set compound contributing to the model of interest.</p> <p>Results</p> <p>The method was applied to partial least-squares models built using 2D (molecular hologram) or 3D (molecular field) descriptors applied to mid-sized training sets (<it>N </it>= 75) drawn from a large (<it>N </it>= 304), well-characterized pool of cyclooxygenase inhibitors. The observed variation in predictive error for the external 229 compound test sets was compared with the uncertainty estimates from DPRESS. Good qualitative and quantitative agreement was seen between the distributions of predictive error observed and those predicted using DPRESS. Inclusion of the distance-dependent term was essential to getting good agreement between the estimated uncertainties and the observed distributions of predictive error. The uncertainty estimates derived by DPRESS were conservative even when the training set was biased, but not excessively so.</p> <p>Conclusion</p> <p>DPRESS is a straightforward and powerful way to reliably estimate individual predictive uncertainties for compounds outside the training set based on their distance to the training set and the internal predictive uncertainty associated with its nearest neighbor in that set. It represents a sample-based, <it>a posteriori </it>approach to defining applicability domains in terms of localized uncertainty.</p

CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in ⩾50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC50 values of 2–7 ng ml−1. MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours

Chemical Analysis of Cellular and Extracellular Carbohydrates of a Biofilm-Forming Strain Pseudomonas aeruginosa PA14

Background: Pseudomonas aeruginosa is a Gram-negative bacterium and an opportunistic pathogen, which causes persisting life-threatening infections in cystic fibrosis (CF) patients. Biofilm mode of growth facilitates its survival in a variety of environments. Most P. aeruginosa isolates, including the non-mucoid laboratory strain PA14, are able to form a thick pellicle, which results in a surface-associated biofilm at the air-liquid (A\ufffdL) interface in standing liquid cultures. Exopolysaccharides (EPS) are considered as key components in the formation of this biofilm pellicle. In the non-mucoid P. aeruginosa strain PA14, the \ufffd\ufffdscaffolding\ufffd\ufffd polysaccharides of the biofilm matrix, and the molecules responsible for the structural integrity of rigid A\ufffdL biofilm have not been identified. Moreover, the role of LPS in this process is unclear, and the chemical structure of the LPS O-antigen of PA14 has not yet been elucidated. Principal Findings: In the present work we carried out a systematic analysis of cellular and extracellular (EC) carbohydrates of P. aeruginosa PA14. We also elucidated the chemical structure of the LPS O-antigen by chemical methods and 2-D NMR spectroscopy. Our results showed that it is composed of linear trisaccharide repeating units, identical to those described for P. aeruginosa Lanyi type O:2a,c (Lanyi-Bergman O-serogroup 10a, 10c; IATS serotype 19) and having the following structure: -4)-a-L-GalNAcA-(1\ufffd3)-a-D-QuiNAc-(1\ufffd3)- a-L-Rha-(1-. Furthermore, an EC O-antigen polysaccharide (EC O-PS) and the glycerol-phosphorylated cyclic b-(1,3)-glucans were identified in the culture supernatant of PA14, grown statically in minimal medium. Finally, the extracellular matrix of the thick biofilm formed at the A-L interface contained, in addition to eDNA, important quantities (at least ,20% of dry weight) of LPS-like material. Conclusions: We characterized the chemical structure of the LPS O-antigen and showed that the O-antigen polysaccharide is an abundant extracellular carbohydrate of PA14. We present evidence that LPS-like material is found as a component of a biofilm matrix of P. aeruginosa.Peer reviewed: YesNRC publication: Ye

A mathematical model of quorum sensing regulated EPS production in biofilm communities

<p>Abstract</p> <p>Background</p> <p>Biofilms are microbial communities encased in a layer of extracellular polymeric substances (EPS). The EPS matrix provides several functional purposes for the biofilm, such as protecting bacteria from environmental stresses, and providing mechanical stability. Quorum sensing is a cell-cell communication mechanism used by several bacterial taxa to coordinate gene expression and behaviour in groups, based on population densities.</p> <p>Model</p> <p>We mathematically model quorum sensing and EPS production in a growing biofilm under various environmental conditions, to study how a developing biofilm impacts quorum sensing, and conversely, how a biofilm is affected by quorum sensing-regulated EPS production. We investigate circumstances when using quorum-sensing regulated EPS production is a beneficial strategy for biofilm cells.</p> <p>Results</p> <p>We find that biofilms that use quorum sensing to induce increased EPS production do not obtain the high cell populations of low-EPS producers, but can rapidly increase their volume to parallel high-EPS producers. Quorum sensing-induced EPS production allows a biofilm to switch behaviours, from a colonization mode (with an optimized growth rate), to a protection mode.</p> <p>Conclusions</p> <p>A biofilm will benefit from using quorum sensing-induced EPS production if bacteria cells have the objective of acquiring a thick, protective layer of EPS, or if they wish to clog their environment with biomass as a means of securing nutrient supply and outcompeting other colonies in the channel, of their own or a different species.</p

Variation in diabetes care by age: opportunities for customization of care

BACKGROUND: The quality of diabetes care provided to older adults has usually been judged to be poor, but few data provide direct comparison to other age groups. In this study, we hypothesized that adults age 65 and over receive lower quality diabetes care than adults age 45–64 years old. METHODS: We conducted a cohort study of members of a health plan cared for by multiple medical groups in Minnesota. Study subjects were a random sample of 1109 adults age 45 and over with an established diagnosis of diabetes using a diabetes identification method with estimated sensitivity 0.91 and positive predictive value 0.94. Survey data (response rate 86.2%) and administrative databases were used to assess diabetes severity, glycemic control, quality of life, microvascular and macrovascular risks and complications, preventive care, utilization, and perceptions of diabetes. RESULTS: Compared to those aged 45–64 years (N = 627), those 65 and older (N = 482) had better glycemic control, better health-related behaviors, and perceived less adverse impacts of diabetes on their quality of life despite longer duration of diabetes and a prevalence of cardiovascular disease twice that of younger patients. Older patients did not ascribe heart disease to their diabetes. Younger adults often had explanatory models of diabetes that interfere with effective and aggressive care, and accessed care less frequently. Overall, only 37% of patients were simultaneously up-to-date on eye exams, foot exams, and glycated hemoglobin (A1c) tests within one year. CONCLUSION: These data demonstrate the need for further improvement in diabetes care for all patients, and suggest that customisation of care based on age and explanatory models of diabetes may be an improvement strategy that merits further evaluation