Towards Precision Dermatology: Emerging Role of Proteomic Analysis of the Skin

Background: The skin is the largest organ in the human body and serves as a multilayered protective shield from the environment as well as a sensor and thermal regulator. However, despite its importance, many details about skin structure and function at the molecular level remain incompletely understood. Recent advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics have enabled the quantification and characterization of the proteomes of a number of clinical samples, including normal and diseased skin. Summary: Here, we review the current state of the art in proteomic analysis of the skin. We provide a brief overview of the technique and skin sample collection methodologies as well as a number of recent examples to illustrate the utility of this strategy for advancing a broader understanding of the pathology of diseases as well as new therapeutic options. Key Messages: Proteomic studies of healthy skin and skin diseases can identify potential molecular biomarkers for improved diagnosis and patient stratification as well as potential targets for drug development. Collectively, efforts such as the Human Skinatlas offer improved opportunities for enhancing clinical practice and patient outcomes

Lower bounds in the quantum cell probe model

We introduce a new model for studying quantum data structure problems --- the "quantum cell probe model". We prove a lower bound for the static predecessor problem in the 'address-only' version of this model where, essentially, we allow quantum parallelism only over the 'address lines' of the queries. This model subsumes the classical cell probe model, and many quantum query algorithms like Grover's algorithm fall into this framework. We prove our lower bound by obtaining a round elimination lemma for quantum communication complexity. A similar lemma was proved by Miltersen, Nisan, Safra and Wigderson for classical communication complexity, but their proof does not generalise to the quantum setting. We also study the static membership problem in the quantum cell probe model. Generalising a result of Yao, we show that if the storage scheme is 'implicit', that is it can only store members of the subset and 'pointers', then any quantum query scheme must make \Omega(\log n) probes. We also consider the one-round quantum communication complexity of set membership and show tight bounds

Optimal Color Range Reporting in One Dimension

Color (or categorical) range reporting is a variant of the orthogonal range reporting problem in which every point in the input is assigned a \emph{color}. While the answer to an orthogonal point reporting query contains all points in the query range $Q$, the answer to a color reporting query contains only distinct colors of points in $Q$. In this paper we describe an O(N)-space data structure that answers one-dimensional color reporting queries in optimal $O(k+1)$ time, where $k$ is the number of colors in the answer and $N$ is the number of points in the data structure. Our result can be also dynamized and extended to the external memory model

String Indexing for Patterns with Wildcards

We consider the problem of indexing a string $t$ of length $n$ to report the occurrences of a query pattern $p$ containing $m$ characters and $j$ wildcards. Let $occ$ be the number of occurrences of $p$ in $t$, and $\sigma$ the size of the alphabet. We obtain the following results. - A linear space index with query time $O(m+\sigma^j \log \log n + occ)$. This significantly improves the previously best known linear space index by Lam et al. [ISAAC 2007], which requires query time $\Theta(jn)$ in the worst case. - An index with query time $O(m+j+occ)$ using space $O(\sigma^{k^2} n \log^k \log n)$, where $k$ is the maximum number of wildcards allowed in the pattern. This is the first non-trivial bound with this query time. - A time-space trade-off, generalizing the index by Cole et al. [STOC 2004]. We also show that these indexes can be generalized to allow variable length gaps in the pattern. Our results are obtained using a novel combination of well-known and new techniques, which could be of independent interest

Computing discriminating and generic words

International audienceWe study the following three problems of computing generic or discriminating words for a given collection of documents. Given a pattern P and a threshold d, we want to report (i) all longest extensions of P which occur in at least d documents, (ii) all shortest extensions of P which occur in less than d documents, and (iii) all shortest extensions of P which occur only in d selected documents. For these problems, we propose efficient algorithms based on suffix trees and using advanced data structure techniques. For problem (i), we propose an optimal solution with constant running time per output word

Evolutionary conservation of the eumetazoan gene regulatory landscape

Despite considerable differences in morphology and complexity of body plans among animals, a great part of the gene set is shared among Bilateria and their basally branching sister group, the Cnidaria. This suggests that the common ancestor of eumetazoans already had a highly complex gene repertoire. At present it is therefore unclear how morphological diversification is encoded in the genome. Here we address the possibility that differences in gene regulation could contribute to the large morphological divergence between cnidarians and bilaterians. To this end, we generated the first genome-wide map of gene regulatory elements in a nonbilaterian animal, the sea anemone Nematostella vectensis. Using chromatin immunoprecipitation followed by deep sequencing of five chromatin modifications and a transcriptional cofactor, we identified over 5000 enhancers in the Nematostella genome and could validate 75% of the tested enhancers in vivo. We found that in Nematostella, but not in yeast, enhancers are characterized by the same combination of histone modifications as in bilaterians, and these enhancers preferentially target developmental regulatory genes. Surprisingly, the distribution and abundance of gene regulatory elements relative to these genes are shared between Nematostella and bilaterian model organisms. Our results suggest that complex gene regulation originated at least 600 million yr ago, predating the common ancestor of eumetazoans

Beyond Hypergraph Dualization

International audienceThis problem concerns hypergraph dualization and generalization to poset dualization. A hypergraph H = (V, E) consists of a finite collection E of sets over a finite set V , i.e. E ⊆ P(V) (the powerset of V). The elements of E are called hyperedges, or simply edges. A hypergraph is said simple if none of its edges is contained within another. A transversal (or hitting set) of H is a set T ⊆ V that intersects every edge of E. A transversal is minimal if it does not contain any other transversal as a subset. The set of all minimal transversal of H is denoted by T r(H). The hypergraph (V, T r(H)) is called the transversal hypergraph of H. Given a simple hypergraph H, the hypergraph dualization problem (Trans-Enum for short) concerns the enumeration without repetitions of T r(H). The Trans-Enum problem can also be formulated as a dualization problem in posets. Let (P, ≤) be a poset (i.e. ≤ is a reflexive, antisymmetric, and transitive relation on the set P). For A ⊆ P , ↓ A (resp. ↑ A) is the downward (resp. upward) closure of A under the relation ≤ (i.e. ↓ A is an ideal and ↑ A a filter of (P, ≤)). Two antichains (B + , B −) of P are said to be dual if ↓ B + ∪ ↑ B − = P and ↓ B + ∩ ↑ B − = ∅. Given an implicit description of a poset P and an antichain B + (resp. B −) of P , the poset dualization problem (Dual-Enum for short) enumerates the set B − (resp. B +), denoted by Dual(B +) = B − (resp. Dual(B −) = B +). Notice that the function dual is self-dual or idempotent, i.e. Dual(Dual(B)) = B

Bridging the gap: an exploration of the use and impact of positive action in the UK

Despite laws in Britain permitting limited positive action initiatives to combat disadvantage faced by minority groups in employment since the mid-1970s, the subject has notoriously been a neglected and highly controversial area in the UK. Notwithstanding the potential provided by sections 158 and 159 of the Equality Act 2010, it still appears that organisations prefer to steer clear of this opportunity to address disadvantage suffered by protected groups. Whilst there is a body of work considering the theoretical importance of positive action in the UK, there is a lack of empirical exploration of the practical implications of these provisions. This paper will provide a brief overview of the theoretical context and current positive action legislative provisions within the UK. In light of this context, the early findings of a small-scale qualitative study carried out by the authors will be discussed looking at the experiences of a purposive sample of public and private employers in relation to the positive action provisions of the Equality Act 2010. Early research findings suggest that whilst there was a clear willingness and openness by employers to use of outreach measures in order to redress disadvantage, there was evident wariness regarding a move towards preferential treatment as expounded by section 159. Whilst respondents appeared to appreciate the business case for and utility of the positive action measures under section 158, there was far less enthusiasm for more direct preferential treatment, with many respondents raising serious concerns regarding this. These concerns often reflected a highly sensitive risk-based approach towards any action that could expose their organisation to the possibility of “reverse discrimination”

Algorithms for the minimum non-separating path and the balanced connected bipartition problems on grid graphs (With erratum)

For given a pair of nodes in a graph, the minimum non-separating path problem looks for a minimum weight path between the two nodes such that the remaining graph after removing the path is still connected. The balanced connected bipartition (BCP$_2$) problem looks for a way to bipartition a graph into two connected subgraphs with their weights as equal as possible. In this paper we present an algorithm in time $O(N\log N)$ for finding a minimum weight non-separating path between two given nodes in a grid graph of $N$ nodes with positive weight. This result leads to a 5/4-approximation algorithm for the BCP$_2$ problem on grid graphs, which is the currently best ratio achieved in polynomial time. We also developed an exact algorithm for the BCP$_2$ problem on grid graphs. Based on the exact algorithm and a rounding technique, we show an approximation scheme, which is a fully polynomial time approximation scheme for fixed number of rows.Comment: With erratu

Hockey Concussion Education Project, Part 1. Susceptibility-weighted imaging study in male and female ice hockey players over a single season: Clinical article

Object. Concussion, or mild traumatic brain injury (mTBI), is a commonly occurring sports-related injury, especially in contact sports such as hockey. Cerebral microbleeds (CMBs), which appear as small, hypointense lesions on T2*-weighted images, can result from TBI. The authors use susceptibility-weighted imaging (SWI) to automatically detect small hypointensities that may be subtle signs of chronic and acute damage due to both subconcussive and concussive injury. The goal was to investigate how the burden of these hypointensities changes over time, over a playing season, and postconcussion, in comparison with subjects who did not suffer a medically observed and diagnosed concussion. Methods. Images were obtained in 45 university-level adult male and female ice hockey players before and after a single Canadian Interuniversity Sports season. In addition, 11 subjects (5 men and 6 women) underwent imaging at 72 hours, 2 weeks, and 2 months after concussion. To identify subtle changes in brain tissue and potential CMBs, nonvessel clusters of hypointensities on SWI were automatically identified, and a hypointensity burden index was calculated for all subjects at the beginning of the season (BOS), the end of the season (EOS), and at postconcussion time points (where applicable). Results. A statistically significant increase in the hypointensity burden, relative to the BOS, was observed for male subjects with concussions at the 2-week postconcussion time point. A smaller, nonsignificant rise in the burden for female subjects with concussions was also observed within the same time period. There were no significant changes in burden for nonconcussed subjects of either sex between the BOS and EOS time points. However, there was a statistically significant difference in the burden between male and female subjects in the nonconcussed group at both the BOS and EOS time points, with males having a higher burden. Conclusions. This method extends the utility of SWI from the enhancement and detection of larger (\u3e 5 mm) CMBs, which are often observed in more severe cases of TBI, to cases involving smaller lesions in which visual detection of injury is difficult. The hypointensity burden metric proposed here shows statistically significant changes over time in the male subjects. A smaller, nonsignificant increase in the burden metric was observed in the female subjects. ©AANS, 2014