A model-based multithreshold method for subgroup identification

Thresholding variable plays a crucial role in subgroup identification for personalizedmedicine. Most existing partitioning methods split the sample basedon one predictor variable. In this paper, we consider setting the splitting rulefrom a combination of multivariate predictors, such as the latent factors, principlecomponents, and weighted sum of predictors. Such a subgrouping methodmay lead to more meaningful partitioning of the population than using a singlevariable. In addition, our method is based on a change point regression modeland thus yields straight forward model-based prediction results. After choosinga particular thresholding variable form, we apply a two-stage multiple changepoint detection method to determine the subgroups and estimate the regressionparameters. We show that our approach can produce two or more subgroupsfrom the multiple change points and identify the true grouping with high probability.In addition, our estimation results enjoy oracle properties. We design asimulation study to compare performances of our proposed and existing methodsand apply them to analyze data sets from a Scleroderma trial and a breastcancer study

Developmental genetics basis of life history variation in Arabidopsis lyrata

Organisms differ in resource allocation and life-history strategies – an adaptive process that has reproduced great diversity of life on earth. Functional tradeoffs between growth and reproduction are an important determinant of lifetime fitness in iteroparous organisms, with optima varying by the environment. However, the developmental genetics context of the life-history tradeoff problem has been poorly studied. Arabidopsis lyrata, a relative of the annual A. thaliana, provides an excellent model to study life-history tradeoffs' developmental and genetic basis, given its wide climatic distribution and life-history variation. Past research suggests that variation in apical dominance could be an essential aspect of life-history tradeoffs between populations. Auxin transport and signaling constitute major factors affecting apical dominance. Therefore, the primary objective of my study was to test the hypothesis that regulation of auxin transport underlies life-history variation in A. lyrata, specifically between two highly divergent populations, from Mayodan (North Carolina, USA) and Spiterstulen (Norway). My first objective was to test the effects of auxin transport on life-history traits in A. lyrata, which showed mild evidence of variation consistent with the actual differences between the populations. My next objective was to identify cis-regulatory variation in genes within major life-history QTL mapped in a previous study using allele-specific expression (ASE) analyses in F1 hybrids. The result showed significant differences in ASE of PIN3, which encodes a major auxin transport regulator. Overall, this research advances our understanding of life-history variation's developmental and genetic basis and supports the hypothesis that developmental variation in early life stages can be a key mechanism governing plant life-history tradeoffs

Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results

We consider one of the most important problems in directional statistics, namely the problem of testing the null hypothesis that the spike direction $\theta$ of a Fisher-von Mises-Langevin distribution on the $p$-dimensional unit hypersphere is equal to a given direction $\theta_0$. After a reduction through invariance arguments, we derive local asymptotic normality (LAN) results in a general high-dimensional framework where the dimension $p_n$ goes to infinity at an arbitrary rate with the sample size $n$, and where the concentration $\kappa_n$ behaves in a completely free way with $n$, which offers a spectrum of problems ranging from arbitrarily easy to arbitrarily challenging ones. We identify various asymptotic regimes, depending on the convergence/divergence properties of $(\kappa_n)$, that yield different contiguity rates and different limiting experiments. In each regime, we derive Le Cam optimal tests under specified $\kappa_n$ and we compute, from the Le Cam third lemma, asymptotic powers of the classical Watson test under contiguous alternatives. We further establish LAN results with respect to both spike direction and concentration, which allows us to discuss optimality also under unspecified $\kappa_n$. To investigate the non-null behavior of the Watson test outside the parametric framework above, we derive its local asymptotic powers through martingale CLTs in the broader, semiparametric, model of rotationally symmetric distributions. A Monte Carlo study shows that the finite-sample behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure

Are we failing to protect threatened mangroves in the Sundarbans world heritage ecosystem?

The Sundarbans, the largest mangrove ecosystem in the world, is under threat from historical and future human exploitation and sea level rise. Limited scientific knowledge on the spatial ecology of the mangroves in this world heritage ecosystem has been a major impediment to conservation efforts. Here, for the first time, we report on habitat suitability analyses and spatial density maps for the four most prominent mangrove species - Heritiera fomes, Excoecaria agallocha, Ceriops decandra and Xylocarpus mekongensis. Globally endangered H. fomes abundances declined as salinity increased. Responses to nutrients, elevation, and stem density varied between species. H. fomes and X. mekongensis preferred upstream habitats. E. agallocha and C. decandra preferred down-stream and mid-stream habitats. Historical harvesting had negative influences on H. fomes, C. decandra and X. mekongensis abundances. The established protected area network does not support the most suitable habitats of these threatened species. We therefore recommend a reconfiguration of the network to include these suitable habitats and ensure their immediate protection. These novel habitat insights and spatial predictions can form the basis for future forest studies and spatial conservation planning, and have implications for more effective conservation of the Sundarbans mangroves and the many other species that rely on them

Generalized linear model for interval mapping of quantitative trait loci

We developed a generalized linear model of QTL mapping for discrete traits in line crossing experiments. Parameter estimation was achieved using two different algorithms, a mixture model-based EM (expectation–maximization) algorithm and a GEE (generalized estimating equation) algorithm under a heterogeneous residual variance model. The methods were developed using ordinal data, binary data, binomial data and Poisson data as examples. Applications of the methods to simulated as well as real data are presented. The two different algorithms were compared in the data analyses. In most situations, the two algorithms were indistinguishable, but when large QTL are located in large marker intervals, the mixture model-based EM algorithm can fail to converge to the correct solutions. Both algorithms were coded in C++ and interfaced with SAS as a user-defined SAS procedure called PROC QTL

Preservation and recovery of mangrove ecosystem carbon stocks in abandoned shrimp ponds

Mangrove forests capture and store exceptionally large amounts of carbon and are increasingly recognised as an important ecosystem for carbon sequestration. Yet land-use change in the tropics threatens this ecosystem and its critical ‘blue carbon’ (carbon stored in marine and coastal habitats) stores. The expansion of shrimp aquaculture is among the major causes of mangrove loss globally. Here, we assess the impact of mangrove to shrimp pond conversion on ecosystem carbon stocks, and carbon losses and gains over time after ponds are abandoned. Our assessment is based on an intensive field inventory of carbon stocks at a coastal setting in Thailand. We show that although up to 70% of ecosystem carbon is lost when mangroves are converted to shrimp ponds, some abandoned ponds contain deep mangrove soils (>2.5 m) and large carbon reservoirs exceeding 865 t carbon per hectare. We also found a positive recovery trajectory for carbon stocks in the upper soil layer (0-15 cm) of a chronosequence of abandoned ponds, associated with natural mangrove regeneration. Our data suggest that mangrove carbon pools can rebuild in abandoned ponds over time in areas exposed to tidal flushing

Use of Mangroves by Lemurs

Despite an increasing recognition of the ecosystem services provided by mangroves, we know little about their role in maintaining terrestrial biodiversity, including primates. Madagascar’s lemurs are a top global conservation priority with 94 % of species threatened with extinction, but records of their occurrence in mangroves are scarce. I used a mixed-methods approach to collect published and unpublished observations of lemurs in mangroves: I carried out a systematic literature search, and supplemented this with a targeted information request to 1243 researchers, conservation and tourism professionals and others who may have visited mangroves in Madagascar. I found references to, or observations of, at least 23 species in five families using mangroves, representing more than 20 % of lemur species and over 50 % of species whose distributions include mangrove areas. Lemurs used mangroves for foraging, sleeping and travelling between terrestrial forest patches, and some were observed as much as 3 km from the nearest permanently dry land. However most records were anecdotal and thus tell us little about lemur ecology in this habitat. Mangroves are more widely used by lemurs than has previously been recognised, and merit greater attention from primate researchers and conservationists in Madagascar

Blue carbon stock of the Bangladesh Sundarban mangroves: what could be the scenario after a century?

The total blue carbon stock of the Bangladesh Sundarban mangroves was evaluated and the probable future status after a century was predicted based on the recent trend of changes in the last 30 years and implementing a hybrid model of Markov Chain and Cellular automata. At present 36.24 Tg C and 54.95 Tg C are stored in the above-ground and below-ground compartments respectively resulting in total blue carbon stock of 91.19 Tg C. According to the prediction 15.88 Tg C would be lost from this region by the year 2115. The low saline species composition classes dominated mainly by Heritiera spp. accounts for the major portion of the carbon sock at present (45.60 Tg C), while the highly saline regions stores only 14.90 Tg C. The prediction shows that after a hundred years almost 22.42 Tg C would be lost from the low saline regions accompanied by an increase of 8.20 Tg C in the high saline regions dominated mainly by Excoecaria sp. and Avicennia spp. The net carbon loss would be due to both mangrove area loss (~ 510 km2) and change in species composition leading to 58.28 Tg of potential CO2 emission within the year 2115

Structural Basis for Dual-Inhibition Mechanism of a Non-Classical Kazal-Type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin

Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for the regulation of host-pathogen interactions and antimicrobial activities. Serine protease inhibitors, 9.3-kDa CrSPI isoforms 1 and 2, have been identified from the hepatopancreas of the horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki = 1.43 nM). CrSPI has been grouped with the non-classical Kazal-type inhibitors due to its unusual cysteine distribution. Here we report the crystal structure of CrSPI-1 in complex with subtilisin at 2.6 Å resolution and the results of biophysical interaction studies. The CrSPI-1 molecule has two domains arranged in an extended conformation. These two domains act as heads that independently interact with two separate subtilisin molecules, resulting in the inhibition of subtilisin activity at a ratio of 1:2 (inhibitor to protease). Each subtilisin molecule interacts with the reactive site loop from each domain of CrSPI-1 through a standard canonical binding mode and forms a single ternary complex. In addition, we propose the substrate preferences of each domain of CrSPI-1. Domain 2 is specific towards the bacterial protease subtilisin, while domain 1 is likely to interact with the host protease, Furin. Elucidation of the structure of the CrSPI-1: subtilisin (1∶2) ternary complex increases our understanding of host-pathogen interactions in the innate immune system at the molecular level and provides new strategies for immunomodulation