A Bast-like valve in the pigeon?

The first description of the presence of a utriculo-endolymphatic valve in human fetuses was given by Bast in 1928. Since then this valve-like structure is called Bast’s valve. Its exact function has not yet been established. The general opinion is that it has a protective function by having the possibility to separate the superior endolymphatic compartments of the labyrinth from the inferior compartment. Phylogenetically seen birds are the first vertebrates with a cochlear duct and a distinct inferior and superior part of the labyrinth. A structure in the pigeon inner ear, resembling Bast’s valve in mammals, is described

An Efficient Index for Reachability Queries in Public Transport Networks

Computing path queries such as the shortest path in public transport networks is challenging because the path costs between nodes change over time. A reachability query from a node at a given start time on such a network retrieves all points of interest (POIs) that are reachable within a given cost budget. Reachability queries are essential building blocks in many applications, for example, group recommendations, ranking spatial queries, or geomarketing. We propose an efficient solution for reachability queries in public transport networks. Currently, there are two options to solve reachability queries. (1) Execute a modified version of Dijkstra’s algorithm that supports time-dependent edge traversal costs; this solution is slow since it must expand edge by edge and does not use an index. (2) Issue a separate path query for each single POI, i.e., a single reachability query requires answering many path queries. None of these solutions scales to large networks with many POIs. We propose a novel and lightweight reachability index. The key idea is to partition the network into cells. Then, in contrast to other approaches, we expand the network cell by cell. Empirical evaluations on synthetic and real-world networks confirm the efficiency and the effectiveness of our index-based reachability query solution

Cyclin G1 regulates the outcome of taxane-induced mitotic checkpoint arrest

Anti-mitotic chemotherapeutic agents such as taxanes activate the spindle assembly checkpoint (SAC) to arrest anaphase onset, but taxane-exposed cells eventually undergo slippage to exit mitosis. The therapeutic efficacy of taxanes depends on whether slippage after SAC arrest culminates in continued cell survival, or in death by apoptosis. However, the mechanisms that determine these outcomes remain unclear. Here, we identify a novel role for cyclin G1 (CCNG1), an atypical cyclin. Increased CCNG1 expression accompanies paclitaxel-induced, SAC-mediated mitotic arrest, independent of p53 integrity or signaling through the SAC component, BUBR1. CCNG1 overexpression promotes cell survival after paclitaxel exposure. Conversely, CCNG1 depletion by RNA interference delays slippage and enhances paclitaxel-induced apoptosis. Consistent with these observations, CCNG1 amplification is associated with significantly shorter post-surgical survival in patients with ovarian cancer who have received adjuvant chemotherapy with taxanes and platinum compounds. Collectively, our findings implicate CCNG1 in regulating slippage and the outcome of taxane-induced mitotic arrest, with potential implications for cancer therapy

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Rare diseases provide a challenge in the evaluation of new therapies. However, orphan drug development is of increasing interest because of the legislation enabling facilitated support by regulatory agencies through scientific advice, and the protection of the molecules with orphan designation. In the landscape of the rare epilepsies, very few syndromes, namely Dravet syndrome, Lennox-Gastaut syndrome and West syndrome, have been subject to orphan drug development. Despite orphan designations for rare epilepsies having dramatically increased in the past 10 years, the number of approved drugs remains limited and restricted to a handful of epilepsy syndromes. In this paper, we describe the current state of orphan drug development for rare epilepsies. We identified a large number of compounds currently under investigation, but mostly in the same rare epilepsy syndromes as in the past. A rationale for further development in rare epilepsies could be based on the match between the drug mechanisms of action and the knowledge of the causative gene mutation or by evidence from animal models. In case of the absence of strong pathophysiological hypotheses, exploratory/basket clinical studies could be helpful to identify a subpopulation that may benefit from the new drug. We provide some suggestions for future improvements in orphan drug development such as promoting paediatric drug investigations, better evaluation of the incidence and the prevalence, together with the natural history data, and the development of new primary outcomes

The challenges of developing rainfall intensity-duration-frequency curves and national flood hazard maps for the Caribbean

In many Caribbean countries a lack of established good practice methods means that engineers and planners are often unable to plan for and mitigate floods effectively. In most Caribbean states rainfall intensity – duration – frequency (IDF) curves are not readily available. This is a result of the limited quantity of short duration rainfall data available and also because the few IDF curves that have been developed in the region are generally not in the public domain. The lack of readily available IDF curves in the region often results in engineers responsible for the design of key infrastructure inappropriately “transferring” IDF curves developed for islands, where rainfall is less intense, for use in their designs. There are no countries in the Caribbean with nationally consistent flood hazard maps. This often leaves spatial and emergency planners with insufficient information to make important strategic decisions. This paper details the challenges that were faced in producing rainfall IDF curves for return periods up to 1 in 50 years and nationally consistent extreme fluvial flood extent maps with limited data for selected countries within the Caribbean. Recommendations are made for the future development of rainfall IDF curves and national flood maps in the region both in terms of data and organisational requirements

Travelling on Graphs with Small Highway Dimension

We study the Travelling Salesperson (TSP) and the Steiner Tree problem (STP) in graphs of low highway dimension. This graph parameter was introduced by Abraham et al. [SODA 2010] as a model for transportation networks, on which TSP and STP naturally occur for various applications in logistics. It was previously shown [Feldmann et al. ICALP 2015] that these problems admit a quasi-polynomial time approximation scheme (QPTAS) on graphs of constant highway dimension. We demonstrate that a significant improvement is possible in the special case when the highway dimension is 1, for which we present a fully-polynomial time approximation scheme (FPTAS). We also prove that STP is weakly NP-hard for these restricted graphs. For TSP we show NP-hardness for graphs of highway dimension 6, which answers an open problem posed in [Feldmann et al. ICALP 2015]

Automatic Knowledge Extraction from OCR Documents Using Hierarchical Document Analysis

Industries can improve their business efficiency by analyzing and extracting relevant knowledge from large numbers of documents. Knowledge extraction manually from large volume of documents is labor intensive, unscalable and challenging. Consequently, there have been a number of attempts to develop intelligent systems to automatically extract relevant knowledge from OCR documents. Moreover, the automatic system can improve the capability of search engine by providing application-specific domain knowledge. However, extracting the efficient information from OCR documents is challenging due to highly unstructured format. In this paper, we propose an efficient framework for a knowledge extraction system that takes keywords based queries and automatically extracts their most relevant knowledge from OCR documents by using text mining techniques. The framework can provide relevance ranking of knowledge to a given query. We tested the proposed framework on corpus of documents at GE Power where document consists of more than hundred pages in PDF

Exploiting Available Memory and Disk for Scalable Instant Overview Search

Abstract. Search-As-You-Type (or Instant Search) is a recently intro-duced functionality which shows predictive results while the user types a query letter by letter. In this paper we generalize and propose an ex-tension of this technique which apart from showing on-the-fly the first page of results, it shows various other kinds of information, e.g. the outcome of results clustering techniques, or metadata-based groupings of the results. Although this functionality is more informative than the classic search-as-you type, since it combines Autocompletion, Search-As-You-Type, and Results Clustering, the provision of real-time interaction is more challenging. To tackle this issue we propose an approach based on pre-computed information and we comparatively evaluate various in-dex structures for making real-time interaction feasible, even if the size of the available memory space is limited. This comparison reveals the mem-ory/performance trade-off and allows deciding which index structure to use according to the available main memory and desired performance. Furthermore we show that an incremental algorithm can be used to keep the index structure fresh.

Pelvic mass associated with raised CA 125 for benign condition: a case report

<p>Abstract</p> <p>Background</p> <p>Raised CA 125 with associated pelvic mass is highly suggestive of ovarian malignancy, but there are various other benign conditions that can be associated with pelvic mass and a raised CA 125.</p> <p>Case presentation</p> <p>We present a case of 19 year old, Caucasian British woman who presented initially with sudden onset right sided iliac fossa pain and on imaging was found to have 9.8 × 4.5 cm complex cystic mass in right adnexa with a raised CA 125 of 657, which was initially thought to be highly suspicious of cancer but was subsequently found to be due to pelvic inflammatory disease on histology.</p> <p>Conclusion</p> <p>This case highlights the fact that though a pelvic mass with raised CA 125 is highly suggestive of malignancy, pelvic inflammatory disease should always be considered as a differential diagnosis especially in a young patient and a thorough sexual history and screening for pelvic infection should always be carried out in these patients.</p