Trip-Based Public Transit Routing

We study the problem of computing all Pareto-optimal journeys in a public transit network regarding the two criteria of arrival time and number of transfers taken. We take a novel approach, focusing on trips and transfers between them, allowing fine-grained modeling. Our experiments on the metropolitan network of London show that the algorithm computes full 24-hour profiles in 70 ms after a preprocessing phase of 30 s, allowing fast queries in dynamic scenarios.Comment: Minor corrections, no substantial changes. To be presented at ESA 201

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

Transit Node Routing Reconsidered

Transit Node Routing (TNR) is a fast and exact distance oracle for road networks. We show several new results for TNR. First, we give a surprisingly simple implementation fully based on Contraction Hierarchies that speeds up preprocessing by an order of magnitude approaching the time for just finding a CH (which alone has two orders of magnitude larger query time). We also develop a very effective purely graph theoretical locality filter without any compromise in query times. Finally, we show that a specialization to the online many-to-one (or one-to-many) shortest path further speeds up query time by an order of magnitude. This variant even has better query time than the fastest known previous methods which need much more space.Comment: 19 pages, submitted to SEA'201

The effect of ozone exposure on the release of eicosanoids in guinea-pig BAL fluid in relation to cellular damage and inflammation

The observed effects after ozone exposure strongly depend on ozone concentration and exposure time. We hypothesized that depending on the O3 exposure protocol, mainly either an oxidant damage or an inflammation will determine the O3 toxicity. We compared two different ozone exposure protocols: an acute exposure (3 ppm 2 h) for studying the oxidant damage and an exposure (1 ppm 12 h) where an inflammatory component is also probably involved. We measured LDH activity and protein and albumin exudation as markers for cellular damage. After the acute exposure an increase in LDH activity was measured and after exposure to 1 ppm ozone for 12 h the exudation of protein and albumin was also enhanced. The histological examinations showed a neutrophilic inflammatory response only after exposure to 1 ppm ozone for 12 h. The acute exposure protocol resulted in an increased release of PGE2, PGD2, PGF2α and 6-ketoPGF1α whereas exposure to 1 ppm ozone for 12 h led to an additional release of LTB4. No effects were measured on the release of TxB2 and LTC4/D4/E4. These changed amounts of eicosanoids will probably contribute to the ozone-induced lung function changes

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

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.

Circuit-selective cell-autonomous regulation of inhibition in pyramidal neurons by Ste20-like kinase

Maintaining an appropriate balance between excitation and inhibition is critical for neuronal information processing. Cortical neurons can cell-autonomously adjust the inhibition they receive to individual levels of excitatory input, but the underlying mechanisms are unclear. We describe that Ste20-like kinase (SLK) mediates cell-autonomous regulation of excitation-inhibition balance in the thalamocortical feedforward circuit, but not in the feedback circuit. This effect is due to regulation of inhibition originating from parvalbumin-expressing interneurons, while inhibition via somatostatin-expressing interneurons is unaffected. Computational modeling shows that this mechanism promotes stable excitatory-inhibitory ratios across pyramidal cells and ensures robust and sparse coding. Patch-clamp RNA sequencing yields genes differentially regulated by SLK knockdown, as well as genes associated with excitation-inhibition balance participating in transsynaptic communication and cytoskeletal dynamics. These data identify a mechanism for cell-autonomous regulation of a specific inhibitory circuit that is critical to ensure that a majority of cortical pyramidal cells participate in information coding

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Characterisation of human kallikrein 6/protease M expression in ovarian cancer

Kallikrein 6 (hK6, also known as protease M/zyme/neurosin) is a member of the human kallikrein gene family. We have previously cloned the cDNA for this gene by differential display and shown the overexpression of the mRNA in breast and ovarian primary tumour tissues and cell lines. To thoroughly characterise the expression of this kallikrein in ovarian cancer, we have developed a novel monoclonal antibody specific to hK6 and employed it in immunohistochemistry with a wide range of ovarian tumour samples. The expression was found elevated in 67 of 80 cases of ovarian tumour samples and there was a significant difference in the expression levels between normal and benign ovarian tissues and the borderline and invasive tumours (P&lt;0.001). There was no difference of expression level between different subtypes of tumours. More significantly, high level of kallikrein 6 expression was found in many early-stage and low-grade tumours, and elevated hK6 proteins were found in benign epithelia coexisting with borderline and invasive tissues, suggesting that overexpression of hK6 is an early phenomenon in the development of ovarian cancer. Quantitative real-time reverse transcription-polymerase chain reactions also showed elevated kallikrein 6 mRNA expression in ovarian tumours. Genomic Southern analysis of 19 ovarian tumour samples suggested that gene amplification is one mechanism for the overexpression of hK6 in ovarian cancer

An Essential Difference between the Flavonoids MonoHER and Quercetin in Their Interplay with the Endogenous Antioxidant Network

Antioxidants can scavenge highly reactive radicals. As a result the antioxidants are converted into oxidation products that might cause damage to vital cellular components. To prevent this damage, the human body possesses an intricate network of antioxidants that pass over the reactivity from one antioxidant to another in a controlled way. The aim of the present study was to investigate how the semi-synthetic flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside (monoHER), a potential protective agent against doxorubicin-induced cardiotoxicity, fits into this antioxidant network. This position was compared with that of the well-known flavonoid quercetin. The present study shows that the oxidation products of both monoHER and quercetin are reactive towards thiol groups of both GSH and proteins. However, in human blood plasma, oxidized quercetin easily reacts with protein thiols, whereas oxidized monoHER does not react with plasma protein thiols. Our results indicate that this can be explained by the presence of ascorbate in plasma; ascorbate is able to reduce oxidized monoHER to the parent compound monoHER before oxidized monoHER can react with thiols. This is a major difference with oxidized quercetin that preferentially reacts with thiols rather than ascorbate. The difference in selectivity between monoHER and quercetin originates from an intrinsic difference in the chemical nature of their oxidation products, which was corroborated by molecular quantum chemical calculations. These findings point towards an essential difference between structurally closely related flavonoids in their interplay with the endogenous antioxidant network. The advantage of monoHER is that it can safely channel the reactivity of radicals into the antioxidant network where the reactivity is completely neutralized