CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells.

Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis

Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).

Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities

BACKGROUND: The term endothelial progenitor cells (EPCs) is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs) and outgrowth endothelial cells (OECs). METHODS: Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. RESULTS: Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN) with links to immunity and inflammation (TLRs, CD14, HLAs), whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins) are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. CONCLUSIONS: This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

Distribution of the common lizard (Zootoca vivipara) and landscape favourability for the species in Northern Ireland

The common lizard (Zootoca vivipara) is Ireland’s only native reptile, forming a key part of the island’s biodiversity. However, there is a general paucity of distributional and abundance data for the species. In this study, we collated incidental records for common lizard sightings to define the distribution of the species in Northern Ireland. Maximum entropy modelling was employed to describe species-habitat associations. The resulting predicted landscape favourability was used to evaluate the current status of the species based on the distribution of its maximum potential range in relation to the degree of fragmentation of remaining suitable habitat. In common with previous studies in the Republic of Ireland, sightings were highly clustered indicating under-recording, observer bias, and fragmentation of suitable habitat. A total of 98 records were collated from 1905 to 2009. The species was recorded in 63 (ca. 34%) of 186 × 10 km Northern Irish grid squares. Lizard occurrence was strongly and positively associated with landscapes dominated by heathland, bog and coastal habitats. The single best approximating model correctly classified the presence of lizards in 84.2% of cases. Upland heath, lowland raised bog and sand dune systems are all subject to Habitat Action Plans in Northern Ireland and are threatened by conversion to agriculture, afforestation, invasive species encroachment and infrastructural development. Consequently, remaining common lizard populations are likely to be small, isolated and highly fragmented. Establishment of an ecological network to preserve connectivity of remaining heath and bog will not only benefit remaining common lizard populations but biodiversity in general.

Prevalence and Management of Anaemia in Renal Transplant Recipients: Data from Ten European Centres.

Background: Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. Methods: In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. Results: More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia and also the use of erythropoiesis-stimulating agents were significantly different across the different centres, suggesting substantial practice variations. Conclusions: PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey.

Type II-P supernovae as standardized candles: improvements using near-infrared data

We present the first near-infrared Hubble diagram for Type II-P supernovae (SNe), to further explore their value as distance indicators. We use a modified version of the standardized candle method, which relies on the tight correlation between the absolute magnitudes of Type II-P SNe and their expansion velocities during the plateau phase. Although our sample contains only 12 II-P SNe and they are necessarily local (z

Analysis of Degradation Data of Poly(L-lactide-co-L,D-lactic actide) and Poly(L-lactide) Obtained at Elevated and Physiological Temperatures Using Mathematical Models

The degradation of resorbable polymeric devices often takes months to years. Accelerated testing at elevated temperatures is an attractive but controversial technique. The purposes of this paper include: (a) to provide a summary of the mathematical models required to analyse accelerated degradation data and to indicate the pitfalls of using these models; (b) to improve the model previously developed by Han and Pan; (c) to provide a simple version of the model of Han and Pan with an analytical solution that is convenient to use; (d) to demonstrate the application of the improved model in two different poly(lactic acid) systems. It is shown that the simple analytical relations between molecular weight and degradation time widely used in the literature can lead to inadequate conclusions. In more general situations the rate equations are only part of a complete degradation model. Together with previous works in the literature, our study calls for care in using the accelerated testing technique.

Effect of signal intensity normalization on the multivariate analysis of spectral data in complex 'real-world' datasets

Spectral signal intensities, especially in 'real-world' applications with nonstandardized sample presentation due to uncontrolled variables/factors, commonly require additional spectral processing to normalize signal intensity in an effective way. In this study, we have demonstrated the complexity of choosing a normalization routine in the presence of multiple spectrally distinct constituents by probing a dataset of Raman spectra. Variation in absolute signal intensity (90.1% of total variance) of the Raman spectra of these complex biological samples swamps the variation in useful signals (9.4% of total variance), degrading its diagnostic and evaluative potential.

Data mining approach identifies research priorities and data requirements for resolving the red algal tree of life

Background. The assembly of the tree of life has seen significant progress in recent years but algae and protists have been largely overlooked in this effort. Many groups of algae and protists have ancient roots and it is unclear how much data will be required to resolve their phylogenetic relationships for incorporation in the tree of life. The red algae, a group of primary photosynthetic eukaryotes of more than a billion years old, provide the earliest fossil evidence for eukaryotic multicellularity and sexual reproduction. Despite this evolutionary significance, their phylogenetic relationships are understudied. This study aims to infer a comprehensive red algal tree of life at the family level from a supermatrix containing data mined from GenBank. We aim to locate remaining regions of low support in the topology, evaluate their causes and estimate the amount of data required to resolve them. Results. Phylogenetic analysis of a supermatrix of 14 loci and 98 red algal families yielded the most complete red algal tree of life to date. Visualization of statistical support showed the presence of five poorly supported regions. Causes for low support were identified with statistics about the age of the region, data availability and node density, showing that poor support has different origins in different parts of the tree. Parametric simulation experiments yielded optimistic estimates of how much data will be needed to resolve the poorly supported regions (ca. 103 to ca. 104 nucleotides for the different regions). Nonparametric simulations gave a markedly more pessimistic image, some regions requiring more than 2.8 105 nucleotides or not achieving the desired level of support at all. The discrepancies between parametric and nonparametric simulations are discussed in light of our dataset and known attributes of both approaches. Conclusions. Our study takes the red algae one step closer to meaningful inclusion in the tree of life. In addition to the recovery of stable relationships, the recognition of five regions in need of further study is a significant outcome of this work. Based on our analyses of current availability and future requirements of data, we make clear recommendations for forthcoming research.

Deep molluscan phylogeny: synthesis of palaeontological and neontological data

The position of the earliest-derived living molluscs, the Polyplacophora ( chitons) and shell-less vermiform Aplacophora, remains highly contentious despite many morphological, developmental and molecular studies of extant organisms. These two groups are thought to represent either a basal molluscan grade or a clade (Aculifera) sister to the 'higher' molluscs (Conchifera). These incompatible hypotheses result in very different predictions about the earliest molluscs. A new cladistic analysis incorporating both Palaeozoic and extant molluscs is presented here. Our results support the monophyly of Aculifera and suggest that extant aplacophorans and polyplacophorans both derive from a disparate group of multivalved molluscs in two major clades. Reanalysis of the critical Ordovician taxon 'Helminthochiton' thraivensis shows that this animal lacks a true foot despite bearing polyplacophoran-like valves. Its position within our phylogenetic reconstruction indicates that many fossil 'polyplacophorans' in the order Palaeoloricata are likely to represent footless stem-group aplacophorans. 'H.' thraivensis and similar forms such as Acaenoplax may be morphological stepping stones between chitons and the shell-less aplacophorans. Our results imply that crown-group molluscan synapomorphies include serial repetition, the presence of a foot, a mineralized scleritome and a creeping rather than worm-like mode of life.

Genetic diversity of liver flukes (Fasciola hepatica) from Eastern Europe.

The genetic diversity of liver fluke populations in three different countries from Eastern Europe (Greece, Bulgaria, and Poland) in comparison with available data from other countries was determined. Specifically, SNPs from regions of two nuclear genes, 28S rDNA, ß-tubulin 3 and an informative region of the mitochondrial genome were examined. Two major lineages for the 28S rDNA gene based on the highly polymorphic 105th nucleotide position were found. These lineages were widely and almost equally spread not only through the countries studied but also in other investigated geographical areas. Two basic lineages and additional haplotypes were defined for the mtDNA gene region, consisting of the cytochrome c oxidase subunit III gene, transfer RNA histidine gene and cytochome b gene. The basic lineages were observed within Greek, Bulgarian, and Polish Fasciola hepatica populations but the distribution of additional haplotypes differed between the populations from the three countries. For the ß-tubulin 3 gene multiple polymorphic sites were revealed but no explicit clades. The SNPs were spread unequally in all studied geographical regions with an evident distinction between the Greek and Polish specimens. Additional genotypes for the 28S rDNA region as well as haplotypes of the mtDNA region that were typical for the Greek or Polish populations were observed. Significant polymorphisms for ß-tubulin 3 gene were displayed with decreasing percentage of presence within populations from Greece to Poland. There was an amino acid substitution in ß-tubulin 3 protein found only among Polish specimens. It is hypothesized that genotypic differences between Greek, Bulgarian, and Polish liver fluke populations are due to territorial division and genetic drift in past epochs.

Robust Dynamic Pricing Over Infinite Horizon in The Presence of Model Uncertainty( 2* Journal)

This paper studies a problem of dynamic pricing faced by a retailer with limited inventory, uncertain about the demand rate model, aiming to maximize expected discounted revenue over an infinite time horizon. The retailer doubts his demand model which is generated by historical data and views it as an approximation. Uncertainty in the demand rate model is represented by a notion of generalized relative entropy process, and the robust pricing problem is formulated as a two-player zero-sum stochastic differential game. The pricing policy is obtained through the Hamilton-Jacobi-Isaacs (HJI) equation. The existence and uniqueness of the solution of the HJI equation is shown and a verification theorem is proved to show that the solution of the HJI equation is indeed the value function of the pricing problem. The results are illustrated by an example with exponential nominal demand rate.

How to estimate scavenger fish abundance using baited camera data

Baited cameras are often used for abundance estimation wherever alternative techniques are precluded, e.g. in abyssal systems and areas such as reefs. This method has thus far used models of the arrival process that are deterministic and, therefore, permit no estimate of precision.
Furthermore, errors due to multiple counting of fish and missing those not seen by the camera have restricted the technique to using only the time of first arrival, leaving a lot of data redundant. Here, we reformulate the arrival process using a stochastic model, which allows the precision of abundance
estimates to be quantified. Assuming a non-gregarious, cross-current-scavenging fish, we show that prediction of abundance from first arrival time is extremely uncertain. Using example data, we show
that simple regression-based prediction from the initial (rising) slope of numbers at the bait gives good precision, accepting certain assumptions. The most precise abundance estimates were obtained
by including the declining phase of the time series, using a simple model of departures, and taking account of scavengers beyond the camera’s view, using a hidden Markov model.

TESTING FOR STATIONARITY IN HETEROGENEOUS PANEL DATA IN THE CASE OF MODEL MISSPECIFICATION

This paper investigates the performance of the tests proposed by Hadri and by Hadri and Larsson for testing for stationarity in heterogeneous panel data under model misspecification. The panel tests are based on the well known KPSS test (cf. Kwiatkowski et al.) which considers two models: stationarity around a deterministic level and stationarity around a deterministic trend. There is no study, as far as we know, on the statistical properties of the test when the wrong model is used. We also consider the case of the simultaneous presence of the two types of models in a panel. We employ two asymptotics: joint asymptotic, T, N -> infinity simultaneously, and T fixed and N allowed to grow indefinitely. We use Monte Carlo experiments to investigate the effects of misspecification in sample sizes usually used in practice. The results indicate that the assumption that T is fixed rather than asymptotic leads to tests that have less size distortions, particularly for relatively small T with large N panels (micro-panels) than the tests derived under the joint asymptotics. We also find that choosing a deterministic trend when a deterministic level is true does not significantly affect the properties of the test. But, choosing a deterministic level when a deterministic trend is true leads to extreme over-rejections. Therefore, when unsure about which model has generated the data, it is suggested to use the model with a trend. We also propose a new statistic for testing for stationarity in mixed panel data where the mixture is known. The performance of this new test is very good for both cases of T asymptotic and T fixed. The statistic for T asymptotic is slightly undersized when T is very small (

Arbitrary amplitude ion-acoustic solitary excitations in the presence of excess superthermal electrons

Velocity distribution functions with an excess of superthermal particles are commonly observed in space plasmas, and are effectively modeled by a kappa distribution. They are also found in some laboratory experiments. In this paper we obtain existence conditions for and some characteristics of ion-acoustic solitary waves in a plasma composed of cold ions and kappa-distributed electrons, where kappa>3/2 represents the spectral index. As is the case for the usual Maxwell-Boltzmann electrons, only positive potential solitons are found, and, as expected, in the limit of large kappa one recovers the usual range of possible soliton Mach numbers, viz., 1 < M < 1.58. For lower values of kappa, modeling the presence of a greater superthermal component, the range of accessible Mach numbers is reduced. It is found that the amplitude of the largest possible solitons that may be generated in a given plasma (corresponding to the highest allowed Mach number for the given plasma composition) falls off with decreasing kappa, i.e., an increasing superthermal component. On the other hand, at fixed Mach number, both soliton amplitude and profile steepness increase as kappa is decreased. These changes are seen to be important particularly for kappa < 4, i.e., when the electrons have a "hard" spectrum.