Using airborne LiDAR Survey to explore historic-era archaeological landscapes of Montserrat in the eastern Caribbean

This article describes what appears to be the first archaeological application of airborne LiDAR survey to historic-era landscapes in the Caribbean archipelago, on the island of Montserrat. LiDAR is proving invaluable in extending the reach of traditional pedestrian survey into less favorable areas, such as those covered by dense neotropical forest and by ashfall from the past two decades of active eruptions by the Soufrière Hills volcano, and to sites in localities that are inaccessible on account of volcanic dangers. Emphasis is placed on two aspects of the research: first, the importance of ongoing, real-time interaction between the LiDAR analyst and the archaeological team in the field; and second, the advantages of exploiting the full potential of the three-dimensional LiDAR point cloud data for purposes of the visualization of archaeological sites and features

Utilitarian Mechanism Design for Multiobjective Optimization

In a classic optimization problem, the complete input data is assumed to be known to the algorithm. This assumption may not be true anymore in optimization problems motivated by the Internet where part of the input data is private knowledge of independent selfish agents. The goal of algorithmic mechanism design is to provide (in polynomial time) a solution to the optimization problem and a set of incentives for the agents such that disclosing the input data is a dominant strategy for the agents. In the case of NP-hard problems, the solution computed should also be a good approximation of the optimum. In this paper we focus on mechanism design for multiobjective optimization problems. In this setting we are given a main objective function and a set of secondary objectives which are modeled via budget constraints. Multiobjective optimization is a natural setting for mechanism design as many economical choices ask for a compromise between different, partially conflicting goals. The main contribution of this paper is showing that two of the main tools for the design of approximation algorithms for multiobjective optimization problems, namely, approximate Pareto sets and Lagrangian relaxation, can lead to truthful approximation schemes. By exploiting the method of approximate Pareto sets, we devise truthful deterministic and randomized multicriteria fully polynomial-time approximation schemes (FPTASs) for multiobjective optimization problems whose exact version admits a pseudopolynomial-time algorithm, as, for instance, the multibudgeted versions of minimum spanning tree, shortest path, maximum (perfect) matching, and matroid intersection. Our construction also applies to multidimensional knapsack and multiunit combinatorial auctions. Our FPTASs compute a $(1+\varepsilon)$-approximate solution violating each budget constraint by a factor $(1+\varepsilon)$. When feasible solutions induce an independence system, i.e., when subsets of feasible solutions are feasible as well, we present a PTAS (not violating any constraint), which combines the approach above with a novel monotone way to guess the heaviest elements in the optimum solution. Finally, we present a universally truthful Las Vegas PTAS for minimum spanning tree with a single budget constraint, where one wants to compute a minimum cost spanning tree whose length is at most a given value $L$. This result is based on the Lagrangian relaxation method, in combination with our monotone guessing step and with a random perturbation step (ensuring low expected running time). This result can be derandomized in the case of integral lengths. All the mentioned results match the best known approximation ratios, which are, however, obtained by nontruthful algorithms

White matter correlates of complex processing speed performance in relapsing-remitting multiple sclerosis

Background: Natalizumab (NTZ) exerts a positive impact on cognitive functions in Relapsing Multiple Sclerosis (RRMS). Little is known about the effect of Fingolimod (FIN) on these functions. Objectives: to compare the effect on cognitive functions of 1-year treatment with FIN or NTZ. Methods: All consecutive RRMS scheduled for treatment with NTZ or FIN underwent neuropsychological evaluations using the Brief Repeatable Battery, Stroop Test, Fatigue Severity Scale (FSS) and Beck Depression Inventory (BDI) at baseline and every 12 months. A test was considered failed if the corresponding z-score was 2 standard deviation (SD) below the mean Italian normative values. The Cognitive Impairment Index (CII) as a measure of global cognitive function was calculated for each patient. Patients were propensity score (PS)-matched on a 1-to-1 basis at the time of treatment start using the following covariates: sex, age, prior treatment exposure, relapses prior the treatment, school education, and BDI score. The relapse risk during the treatment was estimated through a Poisson regression model. A generalized linear mixed model for repeated measures with an autoregressive variance-covariance structure was applied to evaluate changes in CII, the mean number of cognitive tests failed and FSS score at 1 year of treatment. Results: the effect of treatment on cognitive functions was evaluated in 62 matched RRMS patients receiving NTZ(n=31) or FIN(n=31). The relapse incidence was not significant different between the treatments (FIN vs NTZ: Incidence rate ratio=0.71, p=0.6). The mean±SD number of cognitive tests failed was significantly reduced only in FIN treated patients (2.8±2.2 vs 1.7±1.8, p=0.0014). The CII significantly improved in both groups (NAT 18.5±6.1 vs 14.5±6.1, p=0.0075; FIN 14.0±7.3 vs 11.5±7.5, p< 0.0001), but there was not a significant interaction between group X time. The FSS was unchanged in both groups. Conclusions: Our results indicates, for the first time, that both NAT and FIN treatments significantly ameliorate cognitive functions in RRMS. Moreover, the effect on the number of tests failed suggest that FIN could have a greater impact on cognition than NTZ. The effect on cognition of these two drugs goes in parallel with the reduction of the relapse rate. This latter finding support the hypothesis that in the short-term, NTZ and FIN, exert a positive impact on cognition likely by means of their anti-inflammatory properties

A haplotype map of allohexaploid wheat reveals distinct patterns of selection on homoeologous genomes

BACKGROUND: Bread wheat is an allopolyploid species with a large, highly repetitive genome. To investigate the impact of selection on variants distributed among homoeologous wheat genomes and to build a foundation for understanding genotype-phenotype relationships, we performed population-scale re-sequencing of a diverse panel of wheat lines. RESULTS: A sample of 62 diverse lines was re-sequenced using the whole exome capture and genotyping-by-sequencing approaches. We describe the allele frequency, functional significance, and chromosomal distribution of 1.57 million single nucleotide polymorphisms and 161,719 small indels. Our results suggest that duplicated homoeologous genes are under purifying selection. We find contrasting patterns of variation and inter-variant associations among wheat genomes; this, in addition to demographic factors, could be explained by differences in the effect of directional selection on duplicated homoeologs. Only a small fraction of the homoeologous regions harboring selected variants overlapped among the wheat genomes in any given wheat line. These selected regions are enriched for loci associated with agronomic traits detected in genome-wide association studies. CONCLUSIONS: Evidence suggests that directional selection in allopolyploids rarely acted on multiple parallel advantageous mutations across homoeologous regions, likely indicating that a fitness benefit could be obtained by a mutation at any one of the homoeologs. Additional advantageous variants in other homoelogs probably either contributed little benefit, or were unavailable in populations subjected to directional selection. We hypothesize that allopolyploidy may have increased the likelihood of beneficial allele recovery by broadening the set of possible selection targets

Variants in CUL4B are Associated with Cerebral Malformations

Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

New approximation algorithms for the achromatic number

The achromatic number of a graph is the greatest number of colors in a coloring of the vertices of the graph such that adjacent vertices get distinct colors and for every pair of colors some vertex of the first color and some vertex of the second color are adjacent. The problem of computing this number is NP-complete for general graphs as proved by Yannakakis and Gavril 1980. The problem is also NP-complete for trees, that was proved by Cairnie and Edwards 1997. Chaudhary and Vishwanathan 1997 gave recently a $7$-approximation algorithm for this problem on trees, and an $O(\sqrt{n})$-approximation algorithm for the problem on graphs with girth (length of the shortest cycle) at least six. We present the first $2$-approximation algorithm for the problem on trees. This is a new algorithm based on different ideas than one by Chaudhary and Vishwanathan 1997. We then give a $1.15$-approximation algorithm for the problem on binary trees and a $1.58$-approximation for the problem on trees of constant degree. We show that the algorithms for constant degree trees can be implemented in linear time. We also present the first $O(n^{3/8})$-approximation algorithm for the problem on graphs with girth at least six. Our algorithms are based on an interesting tree partitioning technique. Moreover, we improve the lower bound of Farber {\em et al.} 1986 for the achromatic number of trees with degree bounded by three