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This paper presents new structural data about mitochondria using correlative light and electron microscopy (CLEM) and cryo-electron tomography. These state-of-the-art structural biology methods allow studying biological objects at nanometer scales under natural conditions. Non-invasiveness of these methods makes them comparable to observing animals in their natural environment on a safari. The paper highlights two areas of research that can only be accomplished using these methods. The study visualized location of the Aβ42 amyloid aggregates in relation to mitochondria to test a hypothesis of development of mitochondrial dysfunction in Alzheimer's disease. The results showed that the Aβ42 aggregates do not interact with mitochondria, although some of them are closely located. Therefore, the study demonstrated that mitochondrial dysfunction is not directly associated with the effects of aggregates on mitochondrial structure. Other processes should be considered as sources of mitochondrial dysfunction. Second unique area presented in this work is high-resolution visualization of the mitochondrial membranes and proteins in them. Analysis of the cryo-ET data reveals toroidal holes in the lamellar structures of cardiac mitochondrial cristae, where ATP synthases are located. The study proposes a new mechanism for sorting and clustering protein complexes in the membrane based on topology. According to this suggestion, position of the OXPHOS system proteins in the membrane is determined by its curvature. High-resolution tomography expands and complements existing ideas about the structural and functional organization of mitochondria. This makes it possible to study the previously inaccessible structural interactions of proteins with each other and with membranes in vivo. [ABSTRACT FROM AUTHOR]

Atmospheric muon neutrinos are produced by meson decays in cosmic-ray-induced air showers. The flux depends on meteorological quantities such as the air temperature, which affects the density of air. Competition between decay and re-interaction of those mesons in the first particle production generations gives rise to a higher neutrino flux when the air density in the stratosphere is lower, corresponding to a higher temperature. A measurement of a temperature dependence of the atmospheric ν μ flux provides a novel method for constraining hadronic interaction models of air showers. It is particularly sensitive to the production of kaons. Studying this temperature dependence for the first time requires a large sample of high-energy neutrinos as well as a detailed understanding of atmospheric properties. We report the significant ( > 10 σ ) observation of a correlation between the rate of more than 260,000 neutrinos, detected by IceCube between 2012 and 2018, and atmospheric temperatures of the stratosphere, measured by the Atmospheric Infrared Sounder (AIRS) instrument aboard NASA's AQUA satellite. For the observed 10 % seasonal change of effective atmospheric temperature we measure a 3.5(3) % change in the muon neutrino flux. This observed correlation deviates by about 2-3 standard deviations from the expected correlation of 4.3 % as obtained from theoretical predictions under the assumption of various hadronic interaction models. [ABSTRACT FROM AUTHOR]

High-energy tau neutrinos are rarely produced in atmospheric cosmic-ray showers or at cosmic particle accelerators, but are expected to emerge during neutrino propagation over cosmic distances due to flavor mixing. When high energy tau neutrinos interact inside the IceCube detector, two spatially separated energy depositions may be resolved, the first from the charged current interaction and the second from the tau lepton decay. We report a novel analysis of 7.5 years of IceCube data that identifies two candidate tau neutrinos among the 60 "High-Energy Starting Events" (HESE) collected during that period. The HESE sample offers high purity, all-sky sensitivity, and distinct observational signatures for each neutrino flavor, enabling a new measurement of the flavor composition. The measured astrophysical neutrino flavor composition is consistent with expectations, and an astrophysical tau neutrino flux is indicated at 2.8 σ significance. [ABSTRACT FROM AUTHOR]

The reconstruction of event-level information, such as the direction or energy of a neutrino interacting in IceCube DeepCore, is a crucial ingredient to many physics analyses. Algorithms to extract this high level information from the detector's raw data have been successfully developed and used for high energy events. In this work, we address unique challenges associated with the reconstruction of lower energy events in the range of a few to hundreds of GeV and present two separate, state-of-the-art algorithms. One algorithm focuses on the fast directional reconstruction of events based on unscattered light. The second algorithm is a likelihood-based multipurpose reconstruction offering superior resolutions, at the expense of larger computational cost. [ABSTRACT FROM AUTHOR]

Non-standard interactions of neutrinos arising in many theories beyond the Standard Model can significantly alter matter effects in atmospheric neutrino propagation through the Earth. In this paper, a search for deviations from the prediction of the standard 3-flavour atmospheric neutrino oscillations using the data taken by the ANTARES neutrino telescope is presented. Ten years of atmospheric neutrino data collected from 2007 to 2016, with reconstructed energies in the range from ∼16 GeV to 100 GeV, have been analysed. A log-likelihood ratio test of the dimensionless coefficients εμτ and εττ − εμμ does not provide clear evidence of deviations from standard interactions. For normal neutrino mass ordering, the combined fit of both coefficients yields a value 1.7σ away from the null result. However, the 68% and 95% confidence level intervals for εμτ and εττ − εμμ, respectively, contain the null value. Best fit values, one standard deviation errors and bounds at the 90% confidence level for these coefficients are given for both normal and inverted mass orderings. The constraint on εμτ is among the most stringent to date and it further restrains the strength of possible non-standard interactions in the μ − τ sector. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is the key whole-body imaging technology for observing processes within a living object providing excellent resolution and contrast between soft tissues. In the present work, we exploited the non-destructive properties of MRI to track longitudinally the dynamic changes that take place in developing pupae of the Emperor Moth (Saturnia pavonia) during the last days before eclosion. While in diapause pupae, body fluid was almost homogeneously distributed over the internal compartments, as soon as wings, legs, flight muscles and the head region were fully developed, a significant redistribution of water levels occurred between thoracic and abdominal regions. During the last two days before eclosion, the developing moths transferred substantial amounts of liquid into the gut and the labial gland, and in case of females, into developing eggs. Concomitantly, the volume of the air sacs increased drastically and their expansion/compression became clearly visible in time-resolved MR images. Furthermore, besides ventilation of the tracheal system, air sacs are likely to serve as volume reservoir for liquid transfer during development of the moths inside their pupal case. In parallel, we were able to monitor noninvasively lipid consumption, cardiac activity and haemolymph circulation during final metamorphosis. [ABSTRACT FROM AUTHOR]

The next generation of water Cherenkov neutrino telescopes in the Mediterranean Sea are under construction offshore France (KM3NeT/ORCA) and Sicily (KM3NeT/ARCA). The KM3NeT/ORCA detector features an energy detection threshold which allows to collect atmospheric neutrinos to study flavour oscillation. This paper reports the KM3NeT/ORCA sensitivity to this phenomenon. The event reconstruction, selection and classification are described. The sensitivity to determine the neutrino mass ordering was evaluated and found to be 4.4 σ if the true ordering is normal and 2.3 σ if inverted, after 3 years of data taking. The precision to measure Δ m 32 2 and θ 23 were also estimated and found to be 85. 10 - 6 eV 2 and (- 3.1 + 1.9) ∘ for normal neutrino mass ordering and, 75. 10 - 6 eV 2 and (- 7.0 + 2.0) ∘ for inverted ordering. Finally, a unitarity test of the leptonic mixing matrix by measuring the rate of tau neutrinos is described. Three years of data taking were found to be sufficient to exclude event rate variations larger than 20% at 3 σ level. [ABSTRACT FROM AUTHOR]

KM3NeT/ORCA is a next-generation neutrino telescope optimised for atmospheric neutrino oscillations studies. In this paper, the sensitivity of ORCA to the presence of a light sterile neutrino in a 3+1 model is presented. After three years of data taking, ORCA will be able to probe the active-sterile mixing angles θ14, θ24, θ34 and the effective angle θμe, over a broad range of mass squared difference ∆ m 41 2 ∼ [10−5, 10] eV2, allowing to test the eV-mass sterile neutrino hypothesis as the origin of short baseline anomalies, as well as probing the hypothesis of a very light sterile neutrino, not yet constrained by cosmology. ORCA will be able to explore a relevant fraction of the parameter space not yet reached by present measurements. [ABSTRACT FROM AUTHOR]

The KM3NeT research infrastructure is under construction in the Mediterranean Sea. It consists of two water Cherenkov neutrino detectors, ARCA and ORCA, aimed at neutrino astrophysics and oscillation research, respectively. Instrumenting a large volume of sea water with ∼ 6200 optical modules comprising a total of ∼ 200 , 000 photomultiplier tubes, KM3NeT will achieve sensitivity to ∼ 10 MeV neutrinos from Galactic and near-Galactic core-collapse supernovae through the observation of coincident hits in photomultipliers above the background. In this paper, the sensitivity of KM3NeT to a supernova explosion is estimated from detailed analyses of background data from the first KM3NeT detection units and simulations of the neutrino signal. The KM3NeT observational horizon (for a 5 σ discovery) covers essentially the Milky-Way and for the most optimistic model, extends to the Small Magellanic Cloud ( ∼ 60 kpc ). Detailed studies of the time profile of the neutrino signal allow assessment of the KM3NeT capability to determine the arrival time of the neutrino burst with a few milliseconds precision for sources up to 5–8 kpc away, and detecting the peculiar signature of the standing accretion shock instability if the core-collapse supernova explosion happens closer than 3–5 kpc, depending on the progenitor mass. KM3NeT's capability to measure the neutrino flux spectral parameters is also presented. [ABSTRACT FROM AUTHOR]

Invasive coronary angiography remains the gold standard for diagnosing coronary artery disease, which may be complicated by both, patient-specific anatomy and image quality. Deep learning techniques aimed at detecting coronary artery stenoses may facilitate the diagnosis. However, previous studies have failed to achieve superior accuracy and performance for real-time labeling. Our study is aimed at confirming the feasibility of real-time coronary artery stenosis detection using deep learning methods. To reach this goal we trained and tested eight promising detectors based on different neural network architectures (MobileNet, ResNet-50, ResNet-101, Inception ResNet, NASNet) using clinical angiography data of 100 patients. Three neural networks have demonstrated superior results. The network based on Faster-RCNN Inception ResNet V2 is the most accurate and it achieved the mean Average Precision of 0.95, F1-score 0.96 and the slowest prediction rate of 3 fps on the validation subset. The relatively lightweight SSD MobileNet V2 network proved itself as the fastest one with a low mAP of 0.83, F1-score of 0.80 and a mean prediction rate of 38 fps. The model based on RFCN ResNet-101 V2 has demonstrated an optimal accuracy-to-speed ratio. Its mAP makes up 0.94, F1-score 0.96 while the prediction speed is 10 fps. The resultant performance-accuracy balance of the modern neural networks has confirmed the feasibility of real-time coronary artery stenosis detection supporting the decision-making process of the Heart Team interpreting coronary angiography findings. [ABSTRACT FROM AUTHOR]

The Glashow resonance describes the resonant formation of a W− boson during the interaction of a high-energy electron antineutrino with an electron1, peaking at an antineutrino energy of 6.3 petaelectronvolts (PeV) in the rest frame of the electron. Whereas this energy scale is out of reach for currently operating and future planned particle accelerators, natural astrophysical phenomena are expected to produce antineutrinos with energies beyond the PeV scale. Here we report the detection by the IceCube neutrino observatory of a cascade of high-energy particles (a particle shower) consistent with being created at the Glashow resonance. A shower with an energy of 6.05 ± 0.72 PeV (determined from Cherenkov radiation in the Antarctic Ice Sheet) was measured. Features consistent with the production of secondary muons in the particle shower indicate the hadronic decay of a resonant W− boson, confirm that the source is astrophysical and provide improved directional localization. The evidence of the Glashow resonance suggests the presence of electron antineutrinos in the astrophysical flux, while also providing further validation of the standard model of particle physics. Its unique signature indicates a method of distinguishing neutrinos from antineutrinos, thus providing a way to identify astronomical accelerators that produce neutrinos via hadronuclear or photohadronic interactions, with or without strong magnetic fields. As such, knowledge of both the flavour (that is, electron, muon or tau neutrinos) and charge (neutrino or antineutrino) will facilitate the advancement of neutrino astronomy.A particle shower detected by the IceCube Neutrino Observatory at the very high energy of the Glashow resonance demonstrates its potential for the study of high-energy particle physics and astrophysics. [ABSTRACT FROM AUTHOR]

Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection from Gene Enrichment) to accurately and impartially identify fusions. FUDGE couples target-selected and strand-specific CRISPR-Cas9 activity for fusion gene driver enrichment — without prior knowledge of fusion partner or breakpoint-location — to long read nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints within 2 days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay for diagnostic pan-cancer fusion detection. Fusion genes are a hallmarks of cancer, though breakpoint-position promiscuity restricts diagnostic detection. Here, the authors present FUDGE, a CRISPR-Cas9-based enrichment strategy for nanopore sequencing to identify target fusions irrespective of genomic breakpoint or fusion partner. [ABSTRACT FROM AUTHOR]

Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of transcription factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental transcription factor SOX6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high SOX6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental transcription factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy. Ewing sarcoma is characterized by the fusion of EWSR1 and FLI1. Here, the authors show that EWSR1-FLI1 increases the activity of the developmental transcription factor SOX6, which promotes tumor growth but also increases sensitivity to oxidative stress. [ABSTRACT FROM AUTHOR]

An offline search for a neutrino counterpart to gravitational-wave (GW) events detected during the second observation run (O2) of Advanced-LIGO and Advanced-Virgo performed with ANTARES data is presented. In addition to the search for long tracks induced by ν μ ( ν ¯ μ ) charged current interactions, a search for showering events induced by interactions of neutrinos of any flavour is conducted. The severe spatial and time coincidence provided by the gravitational-wave alert allows regions above the detector horizon to be probed, extending the ANTARES sensitivity over the entire sky. The results of this all-neutrino-flavour and all-sky time dependent analysis are presented. The search for prompt neutrino emission within ±500 s around the time of six GW events yields no neutrino counterparts. Upper limits on the neutrino spectral fluence and constraints on the isotropic energy radiated via high-energy neutrinos (from a few TeV to a few tens of PeV) are set for each GW event analysed. [ABSTRACT FROM AUTHOR]

KM3NeT is a research infrastructure located in the Mediterranean Sea, that will consist of two deep-sea Cherenkov neutrino detectors. With one detector (ARCA), the KM3NeT Collaboration aims at identifying and studying TeV–PeV astrophysical neutrino sources. With the other detector (ORCA), the neutrino mass ordering will be determined by studying GeV-scale atmospheric neutrino oscillations. The first KM3NeT detection units were deployed at the Italian and French sites between 2015 and 2017. In this paper, a description of the detector is presented, together with a summary of the procedures used to calibrate the detector in-situ. Finally, the measurement of the atmospheric muon flux between 2232–3386 m seawater depth is obtained. [ABSTRACT FROM AUTHOR]

The Neutrino Mass Ordering (NMO) remains one of the outstanding questions in the field of neutrino physics. One strategy to measure the NMO is to observe matter effects in the oscillation pattern of atmospheric neutrinos above ∼ 1 GeV , as proposed for several next-generation neutrino experiments. Moreover, the existing IceCube DeepCore detector can already explore this type of measurement. We present the development and application of two independent analyses to search for the signature of the NMO with three years of DeepCore data. These analyses include a full treatment of systematic uncertainties and a statistically-rigorous method to determine the significance for the NMO from a fit to the data. Both analyses show that the dataset is fully compatible with both mass orderings. For the more sensitive analysis, we observe a preference for normal ordering with a p-value of p IO = 15.3 % and CL s = 53.3 % for the inverted ordering hypothesis, while the experimental results from both analyses are consistent within their uncertainties. Since the result is independent of the value of δ CP and obtained from energies E ν ≳ 5 GeV , it is complementary to recent results from long-baseline experiments. These analyses set the groundwork for the future of this measurement with more capable detectors, such as the IceCube Upgrade and the proposed PINGU detector. [ABSTRACT FROM AUTHOR]

Despite low sensitivity, culture of periprosthetic tissue (PPT) specimens on agars and in broths has traditionally been used for the detection of causative microorganisms in patients suspected for prosthetic joint infection (PJI). The aim of this study was to evaluate the added diagnostic value of culturing PPT in blood culture bottles (BCB) over the conventional combination of standard agar and broth alone. This prospective cohort study was conducted over a 12-month period and included consecutive patients undergoing revision arthroplasty. Overall, 113 episodes from 90 subjects were studied; 45 subjects (50.0%) met the Infectious Diseases Society of America (IDSA) criteria for PJI, of whom the majority (75.6%) had an acute infection. Sensitivity and specificity of culture were assessed using IDSA criteria for PJI as gold standard. Although the increase in sensitivity from 84.44 (CI 70.54; 93.51) to 93.33% (81.73; 98.60) was not significant, added diagnostic value of culturing PPT in BCBs was demonstrated by the significantly higher number of detected pathogens in culture sets with BCBs compared to culture without BCBs (61 pathogens in conventional set versus 89 when BCBs were included for 57 PJI episodes, P = <0.0001). In 17 (29.8%) episodes, microorganisms were cultured from BCBs only, and in 9 (52.9%) of these episodes, virulent pathogens were found. This study demonstrates that PPT culture in BCBs leads to isolation of additional microorganisms, both virulent and low-virulent, which were not cultured with use of agars and broths alone. Isolation of additional causative microorganisms has serious consequences for the treatment strategy in PJI. [ABSTRACT FROM AUTHOR]

Porcine circovirus type 3 (PCV3) was firstly detected in 2016 in USA. Later PCV3 was discovered in Asia, Europe, and South America. The present investigation demonstrates for the first time the circulation of PCV3 among pigs in Russia. The viruses were detected at two geographically distant unrelated commercial farms with records of reproductive failure (abortions, stillbirth), porcine dermatitis, and nephropathy syndrome (PDNS). The two farms were located in the region of Smolensk (western part of Russia) and the region of Tyumen (West Siberia, Russia). We investigated samples collected from pigs of different ages. We performed PCR for the PCV3 DNA detection. The DNA of PCV3 was detected in serum, kidney, heart, spleen, pleural effusion, and peritoneal cavity fluid samples. Two viral genomes were sequenced and the corresponding strains were named PCV3-RU/SM17 (the strain from Smolensk region) and PCV3-RU/TY17 (the strain from Tyumen region). The full genome sequences of both strains were 2000 nucleotides in length and contained at least two ORFs, encoding the Cap and Rep proteins. Full sequence alignment revealed a 99.3% identity between the PCV3-RU/SM17 and PCV3-RU/TY17 strains. Molecular analysis showed that the two strains from Russia are highly homologous to viruses identified in other countries, with a 98.5-99.6% homology for PCV3-RU/TY17 and 97.9-99.0 for PCV3-RU/SM17. The PCV3-RU/SM17 and PCV3-RU/TY17 strains were found to form a monophyletic group in a phylogenetic tree based on PCV3 complete genome sequences. [ABSTRACT FROM AUTHOR]

Advanced LIGO detected a significant gravitational wave signal (GW170104) originating from the coalescence of two black holes during the second observation run on January 4th, 2017. An all-sky high-energy neutrino follow-up search has been made using data from the Antares neutrino telescope, including both upgoing and downgoing events in two separate analyses. No neutrino candidates were found within $$\pm 500$$ s around the GW event time nor any time clustering of events over an extended time window of $$\pm 3$$ months. The non-detection is used to constrain isotropic-equivalent high-energy neutrino emission from GW170104 to less than $$\sim {1.2}\times 10^{{55}}$$ erg for a $$E^{-2}$$ spectrum. This constraint is valid in the energy range corresponding to the 5-95% quantiles of the neutrino flux [3.2 TeV; 3.6 PeV], if the GW emitter was below the Antares horizon at the alert time. [ABSTRACT FROM AUTHOR]

IceCube is a neutrino observatory deployed in the glacial ice at the geographic South Pole. The $$\nu _\mu $$ energy unfolding described in this paper is based on data taken with IceCube in its 79-string configuration. A sample of muon neutrino charged-current interactions with a purity of 99.5% was selected by means of a multivariate classification process based on machine learning. The subsequent unfolding was performed using the software Truee. The resulting spectrum covers an E $$_\nu $$ -range of more than four orders of magnitude from 125 GeV to 3.2 PeV. Compared to the Honda atmospheric neutrino flux model, the energy spectrum shows an excess of more than $$1.9\,\sigma $$ in four adjacent bins for neutrino energies $$E_\nu \ge 177.8\,\text {TeV}$$ . The obtained spectrum is fully compatible with previous measurements of the atmospheric neutrino flux and recent IceCube measurements of a flux of high-energy astrophysical neutrinos. [ABSTRACT FROM AUTHOR]

We present a search for a neutrino signal from darkmatter self-annihilations in theMilkyWay using the Ice-Cube Neutrino Observatory (IceCube). In 1005 days of data we found no significant excess of neutrinos over the background of neutrinos produced in atmospheric air showers from cosmic ray interactions. We derive upper limits on the velocity averaged product of the darkmatter self-annihilation cross section and the relative velocity of the dark matter particles 〈σAv〉. Upper limits are set for darkmatter particle candidate masses ranging from 10GeV up to 1TeV while considering annihilation through multiple channels. This work sets the most stringent limit on a neutrino signal from dark matter with mass between 10 and 100GeV, with a limit of 1.18 · 10-23 cm³s-1 for 100GeV dark matter particles self-annihilating via τ+τ- to neutrinos (assuming the Navarro–Frenk–White dark matter halo profile). [ABSTRACT FROM AUTHOR]

A novel algorithm to reconstruct neutrino-induced particle showers within the ANTARES neutrino telescope is presented. The method achieves a median angular resolution of $$6^\circ $$ for shower energies below 100 TeV. Applying this algorithm to 6 years of data taken with the ANTARES detector, 8 events with reconstructed shower energies above 10 TeV are observed. This is consistent with the expectation of about 5 events from atmospheric backgrounds, but also compatible with diffuse astrophysical flux measurements by the IceCube collaboration, from which 2-4 additional events are expected. A $$90\%$$ C.L. upper limit on the diffuse astrophysical neutrino flux with a value per neutrino flavour of $$\text {E}^2\cdot \Phi ^{90\%} = 4.9 \cdot 10^{-8}\,\mathrm {GeV} \cdot \mathrm {cm^{-2} \cdot s^{-1}\cdot sr^{-1}}$$ is set, applicable to the energy range from 23 TeV to 7.8 PeV, assuming an unbroken $$\text {E}^{-2}$$ spectrum and neutrino flavour equipartition at Earth. [ABSTRACT FROM AUTHOR]

Studying atmospheric neutrino oscillations in the few-GeV range with a multi-megaton detector promises to determine the neutrino mass hierarchy. This is the main science goal pursued by the future KM3NeT/ORCA water Cherenkov detector in the Mediterranean Sea. In this paper, the processes that limit the obtainable resolution in both energy and direction in charged-current neutrino events in the ORCA detector are investigated. These processes include the composition of the hadronic fragmentation products, the subsequent particle propagation and the photon-sampling fraction of the detector. GEANT simulations of neutrino interactions in seawater produced by GENIE are used to study the effects in the 1-20 GeV range. It is found that fluctuations in the hadronic cascade in conjunction with the variation of the inelasticity y are most detrimental to the resolutions. The effect of limited photon sampling in the detector is of significantly less importance. These results will therefore also be applicable to similar detectors/media, such as those in ice. [ABSTRACT FROM AUTHOR]

A prototype detection unit of the KM3NeT deep-sea neutrino telescope has been installed at 3500m depth 80 km offshore the Italian coast. KM3NeT in its final configuration will contain several hundreds of detection units. Each detection unit is a mechanical structure anchored to the sea floor, held vertical by a submerged buoy and supporting optical modules for the detection of Cherenkov light emitted by charged secondary particles emerging from neutrino interactions. This prototype string implements three optical modules with 31 photomultiplier tubes each. These optical modules were developed by the KM3NeT Collaboration to enhance the detection capability of neutrino interactions. The prototype detection unit was operated since its deployment in May 2014 until its decommissioning in July 2015. Reconstruction of the particle trajectories from the data requires a nanosecond accuracy in the time calibration. A procedure for relative time calibration of the photomultiplier tubes contained in each optical module is described. This procedure is based on the measured coincidences produced in the sea by the $$^{40}$$ K background light and can easily be expanded to a detector with several thousands of optical modules. The time offsets between the different optical modules are obtained using LED nanobeacons mounted inside them. A set of data corresponding to 600 h of livetime was analysed. The results show good agreement with Monte Carlo simulations of the expected optical background and the signal from atmospheric muons. An almost background-free sample of muons was selected by filtering the time correlated signals on all the three optical modules. The zenith angle of the selected muons was reconstructed with a precision of about 3 $$^\circ $$ . [ABSTRACT FROM AUTHOR]

Neuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs. We here used whole-exome sequencing, mRNA expression profiling, array CGH and DNA methylation analysis to characterize 16 paired samples at diagnosis and relapse from individuals with neuroblastoma. The mutational burden significantly increased in relapsing tumors, accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression. Promoter methylation patterns were consistent over disease course and were patient specific. Recurrent alterations at relapse included mutations in the putative CHD5 neuroblastoma tumor suppressor, chromosome 9p losses, DOCK8 mutations, inactivating mutations in PTPN14 and a relapse-specific activity pattern for the PTPN14 target YAP. Recurrent new mutations in HRAS, KRAS and genes mediating cell-cell interaction in 13 of 16 relapse tumors indicate disturbances in signaling pathways mediating mesenchymal transition. Our data shed light on genetic alteration frequency, identity and evolution in neuroblastoma. [ABSTRACT FROM AUTHOR]

Analysis of the Fermi-LAT data has revealed two extended structures above and below the Galactic Centre emitting gamma rays with a hard spectrum, the so-called Fermi bubbles. Hadronic models attempting to explain the origin of the Fermi bubbles predict the emission of high-energy neutrinos and gamma rays with similar fluxes. The ANTARES detector, a neutrino telescope located in the Mediterranean Sea, has a good visibility to the Fermi bubble regions. Using data collected from 2008 to 2011 no statistically significant excess of events is observed and therefore upper limits on the neutrino flux in TeV range from the Fermi bubbles are derived for various assumed energy cutoffs of the source. [ABSTRACT FROM AUTHOR]

Atmospheric neutrinos are produced during cascades initiated by the interaction of primary cosmic rays with air nuclei. In this paper, a measurement of the atmospheric $\nu_{\mu} + \bar{\nu}_{\mu}$ energy spectrum in the energy range 0.1–200 TeV is presented, using data collected by the ANTARES underwater neutrino telescope from 2008 to 2011. Overall, the measured flux is ∼25 % higher than predicted by the conventional neutrino flux, and compatible with the measurements reported in ice. The flux is compatible with a single power-law dependence with spectral index γmeas=3.58±0.12. With the present statistics the contribution of prompt neutrinos cannot be established. [ABSTRACT FROM AUTHOR]

The photoproduction of $ \omega$ mesons on LH , C and Nb has been measured for incident photon energies from 900 to 1300MeV using the CB/TAPS detector at ELSA. The $ \omega$ lineshape does not show any significant difference between the LH and the Nb targets. The experiment was motivated by transport calculations that predicted a sensitivity of the $ \omega$ lineshape to in-medium modifications near the production threshold on a free nucleon of $\ensuremath{E_{\gamma}^{lab}=1109}$ MeV. A comparison with recent calculations is given. [ABSTRACT FROM AUTHOR]

The (AntaresModules for Acoustic Detection Under the Sea) AMADEUS systemwithin the (Astronomy with a Neutrino Telescope and Abyss environmental RESsearch) ANTARES neutrino telescope is designed to investigate detection techniques for acoustic signals produced by particle cascades. While passing through a liquid a cascade deposits energy and produces a measurable pressure pulse. This can be used for the detection of neutrinos with energies exceeding 1018 eV. The AMADEUS setup consists of 36 hydrophones grouped in six local clusters measuring about one cubic meter each. This article focuses on acoustic particle detection, the hardware of the AMADEUS detector and techniques used for acoustic signal processing. [ABSTRACT FROM AUTHOR]

The reaction γ p → pπ0η has been studied with the CBELSA detector at the tagged photon beam of the Bonn electron stretcher facility. The reaction shows contributions from Δ+(1232)η , N(1535)+π0 and pa 0(980) as intermediate states. A partial-wave analysis suggests that the reaction proceeds via formation of six Δ -resonances, Δ(1600) P 33 , Δ(1920) P 33 , Δ(1700) D 33 , Δ(1940) D 33 , Δ(1905) F 35 , Δ(2360) D 33 , and two nucleon resonances N(1880) P 11 and N(2200) P 13 , for which pole positions and decay branching ratios are given. [ABSTRACT FROM AUTHOR]