Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation at the SHH locus

During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease

Cyclotron radiation emission spectroscopy signal classification with machine learning in project 8

The cyclotron radiation emission spectroscopy (CRES) technique pioneered by Project 8measures electromagnetic radiation fromindividual electrons gyrating in a backgroundmagnetic field to construct a highly precise energy spectrumfor beta decay studies and other applications. The detector,magnetic trap geometry and electron dynamics give rise to amultitude of complex electron signal structures which carry information about distinguishing physical traits.Withmachine learningmodels, we develop a scheme based on these traits to analyze and classifyCRES signals. Proper understanding and use of these traits will be instrumental to improve cyclotron frequency reconstruction and boost the potential of Project 8 to achieveworld-leading sensitivity on the tritiumendpointmeasurement in the future

Locust: C++ software for simulation of RF detection

The Locust simulation package is a newC++software tool developed to simulate the measurement of time-varying electromagnetic fields using RF detection techniques. Modularity and flexibility allow for arbitrary input signals, while concurrently supporting tight integration with physics-based simulations as input. External signals driven by the Kassiopeia particle tracking package are discussed, demonstrating conditional feedback between Locust and Kassiopeia during software execution. An application of the simulation to the Project8 experiment is described

Analysis of test beam data taken with a prototype of TPC with resistive Micromegas for the T2K Near Detector upgrade

In this paper we describe the performance of a prototype of the High Angle Time Projection Chambers (HA-TPCs) that are being produced for the Near Detector (ND280) upgrade of the T2K experiment. The two HA-TPCs of ND280 will be instrumented with eight Encapsulated Resistive Anode Micromegas (ERAM) on each endplate, thus constituting in total 32 ERAMs. This innovative technique allows the detection of the charge emitted by ionization electrons over several pads, improving the determination of the track position. The TPC prototype has been equipped with the first ERAM module produced for T2K and with the HA-TPC readout electronics chain and it has been exposed to the DESY Test Beam in order to measure spatial and dE/dx resolution. In this paper we characterize the performances of the ERAM and, for the first time, we compare them with a newly developed simulation of the detector response. Spatial resolution better than 800 ${\mu \rm m}$ and dE/dx resolution better than 10% are observed for all the incident angles and for all the drift distances of interest. All the main features of the data are correctly reproduced by the simulation and these performances fully fulfill the requirements for the HA-TPCs of T2K

Characterization of Charge Spreading and Gain of Encapsulated Resistive Micromegas Detectors for the Upgrade of the T2K Near Detector Time Projection Chambers

An upgrade of the near detector of the T2K long baseline neutrino oscillation experiment is currently being conducted. This upgrade will include two new Time Projection Chambers, each equipped with 16 charge readout resistive Micromegas modules. A procedure to validate the performance of the detectors at different stages of production has been developed and implemented to ensure a proper and reliable operation of the detectors once installed. A dedicated X-ray test bench is used to characterize the detectors by scanning each pad individually and to precisely measure the uniformity of the gain and the deposited energy resolution over the pad plane. An energy resolution of about 10% is obtained. A detailed physical model has been developed to describe the charge dispersion phenomena in the resistive Micromegas anode. The detailed physical description includes initial ionization, electron drift, diffusion effects and the readout electronics effects. The model provides an excellent characterization of the charge spreading of the experimental measurements and allowed the simultaneous extraction of gain and RC information of the modules

Measurements of the νμ\nu_{\mu} and νˉμ\bar{\nu}_{\mu}-induced Coherent Charged Pion Production Cross Sections on 12C^{12}C by the T2K experiment

We report an updated measurement of the $\nu_{\mu}$-induced, and the first measurement of the $\bar{\nu}_{\mu}$-induced coherent charged pion production cross section on $^{12}C$ nuclei in the T2K experiment. This is measured in a restricted region of the final-state phase space for which $p_{\mu,\pi} > 0.2$ GeV, $\cos(\theta_{\mu}) > 0.8$ and $\cos(\theta_{\pi}) > 0.6$, and at a mean (anti)neutrino energy of 0.85 GeV using the T2K near detector. The measured $\nu_{\mu}$ CC coherent pion production flux-averaged cross section on $^{12}C$ is $(2.98 \pm 0.37 (stat.) \pm 0.31 (syst.) \substack{ +0.49 \\ -0.00 } \mathrm{ (Q^2\,model)}) \times 10^{-40}~\mathrm{cm}^{2}$. The new measurement of the $\bar{\nu}_{\mu}$-induced cross section on $^{12}{C}$ is $(3.05 \pm 0.71 (stat.) \pm 0.39 (syst.) \substack{ +0.74 \\ -0.00 } \mathrm{(Q^2\,model)}) \times 10^{-40}~\mathrm{cm}^{2}$. The results are compatible with both the NEUT 5.4.0 Berger-Sehgal (2009) and GENIE 2.8.0 Rein-Sehgal (2007) model predictions