Review of the ELI-NP-GBS low level rf and synchronization systems

The Gamma Beam System (GBS) of ELI-NP is a linac based gamma-source in construction at Magurele (RO) by the European consortium EuroGammaS led by INFN. Photons with tunable energy and with intensity and brilliance well beyond the state of the art will be produced by Compton back-scattering between a high quality electron beam (up to 740 MeV) and a 515 nm intense laser pulse. Production of very intense photon flux with narrow bandwidth requires multi-bunch operation at 100 Hz repetition rate. A total of 13 klystrons, 3 S-band (2856 MHz) and 10 C-band (5712 MHz) will power a total of 14 Travelling Wave accelerating sections (2 S-band and 12 C-band) plus 3 S-band Standing Wave cavities (a 1.6 cell RF gun and 2 RF deflectors). Each klystron is individually driven by a temperature stabilized LLRF module, for a maximum flexibility in terms of accelerating gradient, arbitrary pulse shaping (e.g. to compensate beam loading effects in multi-bunch regime) and compensation of long-term thermal drifts. In this paper, the whole LLRF system architecture and bench test results, the RF reference generation and distribution together with an overview of the synchronization system will be described

Proteomic analysis identifies subgroups of patients with active systemic lupus erythematosus

Objective: Systemic lupus erythematosus (SLE) is a clinically and biologically heterogenous autoimmune disease. We aimed to investigate the plasma proteome of patients with active SLE to identify novel subgroups, or endotypes, of patients. Method: Plasma was collected from patients with active SLE who were enrolled in the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR). The plasma proteome was analysed using a data-independent acquisition method, Sequential Window Acquisition of All theoretical mass spectra mass spectrometry (SWATH-MS). Unsupervised, data-driven clustering algorithms were used to delineate groups of patients with a shared proteomic profile. Results: In 223 patients, six clusters were identified based on quantification of 581 proteins. Between the clusters, there were significant differences in age (p = 0.012) and ethnicity (p = 0.003). There was increased musculoskeletal disease activity in cluster 1 (C1), 19/27 (70.4%) (p = 0.002) and renal activity in cluster 6 (C6) 15/24 (62.5%) (p = 0.051). Anti-SSa/Ro was the only autoantibody that significantly differed between clusters (p = 0.017). C1 was associated with p21-activated kinases (PAK) and Phospholipase C (PLC) signalling. Within C1 there were two sub-clusters (C1A and C1B) defined by 49 proteins related to cytoskeletal protein binding. C2 and C6 demonstrated opposite Rho family GTPase and Rho GDI signalling. Three proteins (MZB1, SND1 and AGL) identified in C6 increased the classification of active renal disease although this did not reach statistical significance (p = 0.0617). Conclusions: Unsupervised proteomic analysis identifies clusters of patients with active SLE, that are associated with clinical and serological features, which may facilitate biomarker discovery. The observed proteomic heterogeneity further supports the need for a personalised approach to treatment in SLE

Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women

BackgroundA non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls.MethodsThis was a prospective case–control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression.ResultsThe top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96–0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86–0.9)).ConclusionA patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted

Characterization of the astrophysical diffuse neutrino flux using starting track events in IceCube

A measurement of the diffuse astrophysical neutrino spectrum is presented using IceCube data collected from 2011-2022 (10.3 years). We developed novel detection techniques to search for events with a contained vertex and exiting track induced by muon neutrinos undergoing a charged-current interaction. Searching for these starting track events allows us to not only more effectively reject atmospheric muons but also atmospheric neutrino backgrounds in the southern sky, opening a new window to the sub-100 TeV astrophysical neutrino sky. The event selection is constructed using a dynamic starting track veto and machine learning algorithms. We use this data to measure the astrophysical diffuse flux as a single power law flux (SPL) with a best-fit spectral index of γ=2.58-0.09+0.10 and per-flavor normalization of φper-flavorAstro=1.68-0.22+0.19×10-18×GeV-1 cm-2 s-1 sr-1 (at 100 TeV). The sensitive energy range for this dataset is 3-550 TeV under the SPL assumption. This data was also used to measure the flux under a broken power law, however we did not find any evidence of a low energy cutoff

Elements in the Canine Distemper Virus M 3′ UTR Contribute to Control of Replication Efficiency and Virulence

Canine distemper virus (CDV) is a negative-sense, single-stranded RNA virus within the genus Morbillivirus and the family Paramyxoviridae. The Morbillivirus genome is composed of six transcriptional units that are separated by untranslated regions (UTRs), which are relatively uniform in length, with the exception of the UTR between the matrix (M) and fusion (F) genes. This UTR is at least three times longer and in the case of CDV also highly variable. Exchange of the M-F region between different CDV strains did not affect virulence or disease phenotype, demonstrating that this region is functionally interchangeable. Viruses carrying the deletions in the M 3′ UTR replicated more efficiently, which correlated with a reduction of virulence, suggesting that overall length as well as specific sequence motifs distributed throughout the region contribute to virulence

Observation of seven astrophysical tau neutrino candidates with IceCube

We report on a measurement of astrophysical tau neutrinos with 9.7 years of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ντ events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ντ energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π±/K± decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ντ astrophysical neutrinos. Thus, we rule out the absence of astrophysical ντ at the 5σ level. The measured astrophysical ντ flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations

A Search for Coincident Neutrino Emission from Fast Radio Bursts with Seven Years of IceCube Cascade Events

This paper presents the results of a search for neutrinos that are spatially and temporally coincident with 22 unique, nonrepeating fast radio bursts (FRBs) and one repeating FRB (FRB 121102). FRBs are a rapidly growing class of Galactic and extragalactic astrophysical objects that are considered a potential source of high-energy neutrinos. The IceCube Neutrino Observatory\u27s previous FRB analyses have solely used track events. This search utilizes seven years of IceCube cascade events which are statistically independent of track events. This event selection allows probing of a longer range of extended timescales due to the low background rate. No statistically significant clustering of neutrinos was observed. Upper limits are set on the time-integrated neutrino flux emitted by FRBs for a range of extended time windows

All-sky Search for Transient Astrophysical Neutrino Emission with 10 Years of IceCube Cascade Events

Neutrino flares in the sky are searched for in data collected by IceCube between 2011 and 2021 May. This data set contains cascade-like events originating from charged-current electron neutrino and tau neutrino interactions and all-flavor neutral-current interactions. IceCube’s previous all-sky searches for neutrino flares used data sets consisting of track-like events originating from charged-current muon neutrino interactions. The cascade data set is statistically independent of the track data sets, and while inferior in angular resolution, the low-background nature makes it competitive and complementary to previous searches. No statistically significant flare of neutrino emission was observed in an all-sky scan. Upper limits are calculated on neutrino flares of varying duration from 1 hr to 100 days. Furthermore, constraints on the contribution of these flares to the diffuse astrophysical neutrino flux are presented, showing that multiple unresolved transient sources may contribute to the diffuse astrophysical neutrino flux

Search for Continuous and Transient Neutrino Emission Associated with IceCube’s Highest-energy Tracks: An 11 yr Analysis

IceCube alert events are neutrinos with a moderate-to-high probability of having astrophysical origin. In this study, we analyze 11 yr of IceCube data and investigate 122 alert events and a selection of high-energy tracks detected between 2009 and the end of 2021. This high-energy event selection (alert events + high-energy tracks) has an average probability of ≥0.5 of being of astrophysical origin. We search for additional continuous and transient neutrino emission within the high-energy events’ error regions. We find no evidence for significant continuous neutrino emission from any of the alert event directions. The only locally significant neutrino emission is the transient emission associated with the blazar TXS 0506+056, with a local significance of 3σ, which confirms previous IceCube studies. When correcting for 122 test positions, the global p-value is 0.156 and compatible with the background hypothesis. We constrain the total continuous flux emitted from all 122 test positions at 100 TeV to be below 1.2 × 10−15 (TeV cm2 s)−1 at 90% confidence assuming an E −2 spectrum. This corresponds to 4.5% of IceCube’s astrophysical diffuse flux. Overall, we find no indication that alert events in general are linked to lower-energetic continuous or transient neutrino emission

Search for dark matter from the center of the Earth with 10 years of IceCube data

The nature of Dark Matter (DM) remains one of the most important unresolved questions of fundamental physics. Many models, including Weakly Interacting Massive Particles (WIMPs), assume DM to be a particle and predict a weak coupling with Standard Model matter. If DM particles can scatter off nuclei in the vicinity of a massive object such as a star or a planet, they may lose kinetic energy and become gravitationally trapped in the center of such objects, including Earth. As DM accumulates in the center of the Earth, self-annihilation of WIMPs into Standard Model particles can result in an excess of neutrinos which are detectable at the IceCube Neutrino Observatory, situated at the geographic South Pole. A search for excess neutrinos from these annihilations has been performed using 8 years of IceCube data, and results have been interpreted in the context of a number of WIMP annihilation channels (XX → τ+τ−/W+W−/bb¯) and masses ranging from 10 GeV to 10 TeV. We present the latest results from this analysis and compare the outcome with previous analyses by IceCube and other experiments, showing competitive results, which are even world-leading in some parts of the parameter space