Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes

Ancora is a web resource that provides data and tools for exploring genomic organization of highly conserved noncoding elements for multiple genomes

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

Faster algorithms for 1-mappability of a sequence

In the k-mappability problem, we are given a string x of length n and integers m and k, and we are asked to count, for each length-m factor y of x, the number of other factors of length m of x that are at Hamming distance at most k from y. We focus here on the version of the problem where k = 1. The fastest known algorithm for k = 1 requires time O(mn log n/ log log n) and space O(n). We present two algorithms that require worst-case time O(mn) and O(n log^2 n), respectively, and space O(n), thus greatly improving the state of the art. Moreover, we present an algorithm that requires average-case time and space O(n) for integer alphabets if m = {\Omega}(log n/ log {\sigma}), where {\sigma} is the alphabet size

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

Is there a social gradient of sarcopenia? A meta-analysis and systematic review protocol

Introduction: Sarcopenia (or loss of muscle mass and function) is a relatively new area within the field of musculoskeletal research and medicine. Investigating whether there is a social gradient, including occupation type and income level, of sarcopenia, as observed for other diseases, will contribute significantly to the limited evidence base for this disease. This new information may inform the prevention and management of sarcopenia and widen the evidence base to support existing and future health campaigns. Methods and analysis: We will conduct a systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to identify articles that investigate associations between social determinants of health and sarcopenia in adults aged 50 years and older. Eligibility of the selected studies will be determined by two independent reviewers. The methodological quality of eligible studies will be assessed according to predetermined criteria. Established statistical methods to identify and control for heterogeneity will be used, and where appropriate, we will conduct a meta-analysis. In the event that heterogeneity prevents numerical synthesis, a best evidence analysis will be employed. This systematic review protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines and will be registered with the International Prospective Register of Systematic Reviews (PROSPERO). Ethics and dissemination: This systematic review will use published data, thus ethical permissions will not be required. In addition to peer-reviewed publication, our results will be presented at (inter)national conferences relevant to the field of sarcopenia, ageing and/or musculoskeletal health and disseminated both electronically and in print. PROSPERO registration number: CRD4201707225

Caregiving, Metabolic Syndrome Indicators, and 1-year Decline in Walking Speed: Results of Caregiver-SOF

BACKGROUND Chronic stress may lead to health decline through metabolic syndrome. Thus, persons in stressful caregiving situations who also have more indicators of metabolic syndrome may experience more decline than other caregivers or noncaregivers. METHODS The sample included 921 women (338 caregivers and 583 noncaregivers) from the Caregiver-Study of Osteoporotic Fractures study. Participants had home-based baseline and 1-year follow-up interviews between 1999 and 2003. At baseline, caregivers were categorized as long term (³4 years) versus short term (<4 years), and caring for someone with Alzheimer's disease/dementia or not. A metabolic risk composite score was the sum of four indicators: body mass index ³30, and diagnosis or using medications for hypertension, diabetes, or high cholesterol. Walking speed (m/second) was measured at both interviews. RESULTS Walking speed declined for the total sample (adjusted mean = −0.005 m/second, ±0.16) over an average of 1.04 years (±0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk score was associated with greater decline for the total sample and long-term and dementia caregivers, but not other caregivers or noncaregivers. Metabolic risk score modified the adjusted associations between years of caregiving and dementia caregiving with walking speed decline (p values for interaction terms were 0.039 and 0.057, respectively). The biggest declines were in long-term caregivers and dementia caregivers who also had 3–4 metabolic indicators (−0.10 m/second and −0.155 m/second, respectively). CONCLUSIONS Walking speed declined the most among older women who had both stressful caregiving situations and more metabolic syndrome indicators, suggesting these caregiver subgroups may have increased risk of health decline.AG18037, AG05407, AR35582, AG05394, AR35584, and AR3558

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

Compressed Subsequence Matching and Packed Tree Coloring

We present a new algorithm for subsequence matching in grammar compressed strings. Given a grammar of size $n$ compressing a string of size $N$ and a pattern string of size $m$ over an alphabet of size $\sigma$, our algorithm uses $O(n+\frac{n\sigma}{w})$ space and $O(n+\frac{n\sigma}{w}+m\log N\log w\cdot occ)$ or $O(n+\frac{n\sigma}{w}\log w+m\log N\cdot occ)$ time. Here $w$ is the word size and $occ$ is the number of occurrences of the pattern. Our algorithm uses less space than previous algorithms and is also faster for $occ=o(\frac{n}{\log N})$ occurrences. The algorithm uses a new data structure that allows us to efficiently find the next occurrence of a given character after a given position in a compressed string. This data structure in turn is based on a new data structure for the tree color problem, where the node colors are packed in bit strings.Comment: To appear at CPM '1

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

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