The mass-hierarchy and CP-violation discovery reach of the LBNO long-baseline neutrino experiment

The next generation neutrino observatory proposed by the LBNO collaboration will address fundamental questions in particle and astroparticle physics. The experiment consists of a far detector, in its first stage a 20 kt LAr double phase TPC and a magnetised iron calorimeter, situated at 2300 km from CERN and a near detector based on a highpressure argon gas TPC. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the L/E behaviour, and distinguishing effects arising from δCP and matter. In this paper we have reevaluated the physics potential of this setup for determining the mass hierarchy (MH) and discovering CP-violation (CPV), using a conventional neutrino beam from the CERN SPS with a power of 750 kW. We use conservative assumptions on the knowledge of oscillation parameter priors and systematic uncertainties. The impact of each systematic error and the precision of oscillation prior is shown. We demonstrate that the first stage of LBNO can determine unambiguously the MH to > 5δ C.L. over the whole phase space. We show that the statistical treatment of the experiment is of very high importance, resulting in the conclusion that LBNO has ~ 100% probability to determine the MH in at most 4-5 years of running. Since the knowledge of MH is indispensable to extract δCP from the data, the first LBNO phase can convincingly give evidence for CPV on the 3δ C.L. using today’s knowledge on oscillation parameters and realistic assumptions on the systematic uncertainties.

Novel functional profiling approach combining reverse phase protein microarrays and human 3-D ex vivo tissue cultures: expression of apoptosis-related proteins in human colon cancer

Cancer is caused by a complex pattern of molecular perturbations. To understand the biology of cancer, it is thus important to look at the activation state of key proteins and signaling networks. The limited amount of available sample material from patients and the complexity of protein expression patterns make the use of traditional protein analysis methods particularly difficult. In addition, the only approach that is currently available for performing functional studies is the use of serial biopsies, which is limited by ethical constraints and patient acceptance. The goal of this work was to establish a 3-D ex vivo culture technique in combination with reverse-phase protein microarrays (RPPM) as a novel experimental tool for use in cancer research. The RPPM platform allows the parallel profiling of large numbers of protein analytes to determine their relative abundance and activation level. Cancer tissue and the respective corresponding normal tissue controls from patients with colorectal cancer were cultured ex vivo. At various time points, the cultured samples were processed into lysates and analyzed on RPPM to assess the expression of carcinoembryonic antigen (CEA) and 24 proteins involved in the regulation of apoptosis. The methodology displayed good robustness and low system noise. As a proof of concept, CEA expression was significantly higher in tumor compared with normal tissue (p<0.0001). The caspase 9 expression signal was lower in tumor tissue than in normal tissue (p<0.001). Cleaved Caspase 8 (p=0.014), Bad (p=0.007), Bim (p=0.007), p73 (p=0.005), PARP (p<0.001), and cleaved PARP (p=0.007) were differentially expressed in normal liver and normal colon tissue. We demonstrate here the feasibility of using RPPM technology with 3-D ex vivo cultured samples. This approach is useful for investigating complex patterns of protein expression and modification over time. It should allow functional proteomics in patient samples with various applications such as pharmacodynamic analyses in drug development.

Focal Epilepsy: MR Imaging of Nonhemodynamic Field Effects by Using a Phase-cycled Stimulus-induced Rotary Saturation Approach with Spin-Lock Preparation.

Purpose To investigate whether nonhemodynamic resonant saturation effects can be detected in patients with focal epilepsy by using a phase-cycled stimulus-induced rotary saturation (PC-SIRS) approach with spin-lock (SL) preparation and whether they colocalize with the seizure onset zone and surface interictal epileptiform discharges (IED). Materials and Methods The study was approved by the local ethics committee, and all subjects gave written informed consent. Eight patients with focal epilepsy undergoing presurgical surface and intracranial electroencephalography (EEG) underwent magnetic resonance (MR) imaging at 3 T with a whole-brain PC-SIRS imaging sequence with alternating SL-on and SL-off and two-dimensional echo-planar readout. The power of the SL radiofrequency pulse was set to 120 Hz to sensitize the sequence to high gamma oscillations present in epileptogenic tissue. Phase cycling was applied to capture distributed current orientations. Voxel-wise subtraction of SL-off from SL-on images enabled the separation of T2* effects from rotary saturation effects. The topography of PC-SIRS effects was compared with the seizure onset zone at intracranial EEG and with surface IED-related potentials. Bayesian statistics were used to test whether prior PC-SIRS information could improve IED source reconstruction. Results Nonhemodynamic resonant saturation effects ipsilateral to the seizure onset zone were detected in six of eight patients (concordance rate, 0.75; 95% confidence interval: 0.40, 0.94) by means of the PC-SIRS technique. They were concordant with IED surface negativity in seven of eight patients (0.88; 95% confidence interval: 0.51, 1.00). Including PC-SIRS as prior information improved the evidence of the standard EEG source models compared with the use of uninformed reconstructions (exceedance probability, 0.77 vs 0.12; Wilcoxon test of model evidence, P < .05). Nonhemodynamic resonant saturation effects resolved in patients with favorable postsurgical outcomes, but persisted in patients with postsurgical seizure recurrence. Conclusion Nonhemodynamic resonant saturation effects are detectable during interictal periods with the PC-SIRS approach in patients with epilepsy. The method may be useful for MR imaging-based detection of neuronal currents in a clinical environment. (©) RSNA, 2016 Online supplemental material is available for this article.