Improved base calling for the Illumina Genome Analyzer using machine learning strategies

Ibis is an accurate, fast and easy-to-use base caller for the Illumina Genome Analyzer that reduces error rates and increases output of usable reads

Die Rolle der 12/15-Lipoxygenase in der Anti-Tumor-Immunantwort

12/15-lipoxygenase (12/15-LOX) is a murine enzyme that facilitates the oxygenation of phospholipid (PL)-bound fatty acids, in particular arachidonic acid. Since PLs are the major constituent of biological membranes and modifications to the fatty acid tails largely influence the biophysical properties of biomembranes, 12/15-LOX is thought to be a critical modulator of membrane fluidics as well as PL-mediated signaling in cells of the innate immune response. Recently, it was described that 12/15-LOX is expressed in dendritic cells (DCs) found within secondary lymphatic organs of mice. Here, 12/15-LOX-deficiency was implied with an elevated maturation state of DCs, a lowered activation threshold during CD4 T cell priming, and consequently, an increased potential to develop T-cell-driven auto-immune diseases. As of now, however, data connecting 12/15-LOX to T cell immunity has largely focused on settings that require exogenous antigen presentation in the context of Major Histocompatibility Complex class II (MHC-II). The role of this enzyme during the initiation of a CD8 T cell-driven protective immune response that requires antigen presentation in the context of MHC-I remains largely unexplored. In order to close this critical gap in our understanding of the role that 12/15-LOX occupies in modulating T cell immunity, this work is aimed at identifying the DC subset that primarily expresses 12/15-LOX as well as exploring the consequences of 12/15-LOX deficiency in mounting an efficient anti-tumor T cell response. Herein, it was demonstrated that 12/15-LOX is primarily expressed in DCs of the migratory cDC2 lineage found in murine lymph nodes. Moreover, it was shown that 12/15-LOX ablation results in the inability of mice to reject a syngeneic, but highly immunogenic tumor cell graft, whereas no difference in the anti-tumor response could be identified in a low-immunogenic tumor setting when compared to control animals. Evidence collected in this work points towards inefficient priming of tumor-antigen-specific CD8 T cells with strongly reduced cytotoxic T lymphocyte (CTL) infiltration into late-stage tumors, putting 12/15-LOX-expressing DCs center-stage during initiation of an efficient anti-tumor response.12/15-Lipoxygenase (12/15-LOX) ist ein Enzym der Maus, das die Oxygenierung von Phospholipid (PL)-gebundenen Fettsäuren, insbesondere von Arachidonsäure, katalysiert. PLs sind die Hauptbestandteile aller biologischer Membranen. Modifikationen, die die Fettsäurefortsätze betreffen, beeinflussen zu einem großen Teil die biophysikalischen Eigenschaften dieser Biomembran. Es wird daher angenommen, dass 12/15-LOX ein entscheidender Regulator der Membranfluidität und der PL-assoziierten Signalprozesse in Zellen des angeborenen Immunsystems ist. Kürzlich wurde beschrieben, dass 12/15-LOX in dendritischen Zellen (DZs) der sekundären lymphatischen Organe der Maus exprimiert wird. Darüber hinaus wurde eine 12/15-LOX-Defizienz mit einem erhöhten Reifegrad und eines verringerten Aktivierungsgrenzwerts dieser DZs während der CD4 T-Zell-Aktivierung in Verbindung gebracht, welches sich in einem erhöhten Risiko zur Entwicklung von T-Zell-abhängigen Autoimmunerkrankungen äußert. Derzeit jedoch betreffen Daten, die eine 12/15-LOX-Defizienz mit T-Zell-vermittelter Immunität verbinden, hauptsächlich die Haupthistokompatibilitätskomplex-Klasse-II (MHC-II)-vermittelte T-Zell-Aktivierung, welche auf die Präsentation von Fremd-Antigen spezialisiert ist. Im Gegensatz dazu ist die Rolle des Enzyms in einer CD8-T-Zell-vermittelten, protektiven Immunantwort, welche die Präsentation von Antigenen im MHC-I-Kontext erfordert, weitestgehend unbekannt. Um diese kritische Lücke in unserem Verständnis, wie 12/15-LOX die T-Zell-vermittelte Immunität beeinflusst, zu schließen, soll im Rahmen dieser Arbeit untersucht werden, welche der bisher bekannten DZ-Untergruppen hauptsächlich 12/15-LOX exprimiert und welche Folgen eine 12/15-LOX-Defizienz auf die Initiierung einer T-Zell-vermittelten Anti-Tumor-Antwort hat. Es kann gezeigt werden, dass in murinen Lymphknoten hauptsächlich migratorische, konventionelle Typ 2 DZ 12/15-LOX exprimieren. Darüber hinaus wird anhand von 12/15-LOX-defizienten Mäusen demonstriert, dass ein syngeneisches, jedoch hoch immunogenes Tumorzell-Transplantat in diesen Tieren nicht abgestoßen werden kann, wohingegen sich bei einem wenig immunogenen Transplantat im Vergleich zu Kontrolltieren kein Unterschied in der Anti-Tumor-Antwort erkennen lässt. Die im Rahmen dieser Arbeit gesammelten Hinweise lassen den Schluss zu, dass die Aktivierung von Tumor-Antigen-spezifischen CD8-T-Zellen stark reduziert ist, was sich in einer stark reduzierten Infiltration von Tumoren durch zytotoxische T-Zellen im späten Stadium äußert. 12/15-LOX-exprimierende DZs nehmen daher eine zentrale Rolle während der Initiation einer effektiven Anti-Tumor-Antwort ein

Auctions and fair division games under different price rules: Individual bid functions, prices and efficiency rates

In auctions an outside seIler offers a commodity for sale and collects the revenue w hich is achieved. In fair division games the object is owned by the group of bidders. Consequently the auction's revenue is equally distributed among all bidders. In our experiment participants face four auction types (first versus second price - auction versus fair division game) repeteadly. Due to the strategy method (one bids before learning one's private value) we can investigate the slope and curvature of individual bid functions) the evidence for risk aversion, the comparative statics with respect to the game type, the price expectations and the efficiency rates

The Morphological, Elastic, and Electric Properties of Dust Aggregates in Comets: A Close Look at COSIMA/Rosetta's Data on Dust in Comet 67P/Churyumov-Gerasimenko

The Cometary Secondary Ion Mass Analyzer (COSIMA) onboard ESA's Rosetta orbiter has revealed that dust particles in the coma of Comet 67P/Churyumov-Gerasimenko are aggregates of small grains. We study the morphological, elastic, and electric properties of dust aggregates in the coma of Comet 67P/Churyumov-Gerasimenko using optical microscopic images taken by the COSIMA instrument. Dust aggregates in COSIMA images are well represented as fractals in harmony with morphological data from MIDAS (Micro-Imaging Dust Analysis System) and GIADA (Grain Impact Analyzer and Dust Accumulator) onboard Rosetta. COSIMA's images, together with the data from the other Rosetta's instruments such as MIDAS and GIADA do not contradict the so-called rainout growth of $10~\mu\mathrm{m}$-sized particles in the solar nebula. The elastic and electric properties of dust aggregates measured by COSIMA suggest that the surface chemistry of cometary dust is well represented as carbonaceous matter rather than silicates or ices, consistent with the mass spectra, and that organic matter is to some extent carbonized by solar radiation, as inferred from optical and infrared observations of various comets. Electrostatic lofting of cometary dust by intense electric fields at the terminator of its parent comet is unlikely, unless the surface chemistry of the dust changes from a dielectric to a conductor. Our findings are not in conflict with our current understanding of comet formation and evolution, which begin with the accumulation of condensates in the solar nebula and follow with the formation of a dust mantle in the inner solar system.Comment: 17 pages, 12 figures, 1 tables, to appear in Planetary and Space Scienc

Cross-game Learning and Cognitive Ability in Auctions

Overbidding in sealed-bid second-price auctions (SPAs) has been shown to be persistent and associated with cognitive ability. We study experimentally to what extent cross-game learning can reduce overbidding in SPAs, taking into account cognitive skills. Employing an order-balanced design, we use first-price auctions (FPAs) to expose participants to an auction format in which losses from high bids are more salient than in SPAs. Experience in FPAs causes substantial cross-game learning for cognitively less able participants but does not affect overbidding for the cognitively more able. Vice versa, experiencing SPAs before bidding in an FPA does not substantially affect bidding behavior by the cognitively less able but, somewhat surprisingly, reduces bid shading by cognitively more able participants, resulting in lower profits in FPAs. Thus, 'cross-game learning' may rather be understood as 'cross-game transfer', as it has the potential to benefit bidders with lower cognitive ability whereas it has little or even adverse effects for higher-ability bidders

Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA

DNA sequences determined from ancient organisms have high error rates, primarily due to uracil bases created by cytosine deamination. We use synthetic oligonucleotides, as well as DNA extracted from mammoth and Neandertal remains, to show that treatment with uracil–DNA–glycosylase and endonuclease VIII removes uracil residues from ancient DNA and repairs most of the resulting abasic sites, leaving undamaged parts of the DNA fragments intact. Neandertal DNA sequences determined with this protocol have greatly increased accuracy. In addition, our results demonstrate that Neandertal DNA retains in vivo patterns of CpG methylation, potentially allowing future studies of gene inactivation and imprinting in ancient organisms

Reducing Carbon Emissions from the Tourist Accommodation Sector on Non-Interconnected Islands : A Case Study of a Medium-Sized Hotel in Rhodes, Greece

Acknowledgments: The authors would like to thank Mikhalis Markopoulos and Manolis Markopoulos for their assistance in gathering comprehensive information about the special demands of hotels, the hotel’s energy consumption and energy bills.Peer reviewedPublisher PD

Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment

Introduction: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and treatment have rarely been reported. Methods: Thirty-seven children diagnosed with CNO were treated with naproxen continuously for the first 6 months. If assessment at that time revealed progressive disease or no further improvement, sulfasalazine and short-term corticosteroids were added. The aims of our short-term follow-up study were to describe treatment response in detail and to identify potential risk factors for an unfavorable outcome. Results: Naproxen treatment was highly effective in general, inducing a symptom-free status in 43% of our patients after 6 months. However, four nonsteroidal anti-inflammatory drug (NSAID) partial-responders were additionally treated with sulfasalazine and short-term corticosteroids. The total number of clinical detectable lesions was significantly reduced. Mean disease activity estimated by the patient/physician and the physical aspect of health-related quality of life including functional ability (global assessment/childhood health assessment questionnaire and childhood health assessment questionnaire) and pain improved significantly. Forty-one percent of our patients showed radiological relapses, but 67% of them were clinically silent. Conclusions: Most children show a favorable clinical course in the first year of anti-inflammatory treatment with NSAIDs. Relapses and new radiological lesions can occur at any time and at any site in the skeleton but may not be clinically symptomatic. Whole-body magnetic resonance imaging proved to be very sensitive for initial and follow-up diagnostics

Deep learning-based classification of blue light cystoscopy imaging during transurethral resection of bladder tumors

Bladder cancer is one of the top 10 frequently occurring cancers and leads to most cancer deaths worldwide. Recently, blue light (BL) cystoscopy-based photodynamic diagnosis was introduced as a unique technology to enhance the detection of bladder cancer, particularly for the detection of flat and small lesions. Here, we aim to demonstrate a BL image-based artificial intelligence (AI) diagnostic platform using 216 BL images, that were acquired in four different urological departments and pathologically identified with respect to cancer malignancy, invasiveness, and grading. Thereafter, four pre-trained convolution neural networks were utilized to predict image malignancy, invasiveness, and grading. The results indicated that the classification sensitivity and specificity of malignant lesions are 95.77% and 87.84%, while the mean sensitivity and mean specificity of tumor invasiveness are 88% and 96.56%, respectively. This small multicenter clinical study clearly shows the potential of AI based classification of BL images allowing for better treatment decisions and potentially higher detection rates

Recombinant Goose Circoviruses Circulating in Domesticated and Wild Geese in Poland

Circoviruses are circular single-stranded DNA (ssDNA) viruses that infect a variety of animals, both domestic and wild. Circovirus infection in birds is associated with immunosuppression and this in turn predisposes the infected animals to secondary infections that can lead to mortality. Farmed geese (Anser anser) in many parts of the world are infected with circoviruses. The majority of the current genomic information for goose circoviruses (GoCVs) (n = 40) are from birds sampled in China and Taiwan, and only two genome sequences are available from Europe (Germany and Poland). In this study, we sampled 23 wild and 19 domestic geese from the Gopło Lake area in Poland. We determined the genomes of GoCV from 21 geese; 14 domestic Greylag geese (Anser anser), three wild Greylag geese (A. anser), three bean geese (A. fabalis), and one white fronted goose (A. albifrons). These genomes share 83–95% nucleotide pairwise identities with previously identified GoCV genomes, most are recombinants with exchanged fragment sizes up to 50% of the genome. Higher diversity levels can be seen within the genomes from domestic geese compared with those from wild geese. In the GoCV capsid protein (cp) and replication associated protein (rep) gene sequences we found that episodic positive selection appears to largely mirror those of beak and feather disease virus and pigeon circovirus. Analysis of the secondary structure of the ssDNA genome revealed a conserved stem-loop structure with the G-C rich stem having a high degree of negative selection on these nucleotides