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Neutrino oscillation physics has entered a new precision era, which poses major challenges to the level of control and diagnostics of the neutrino beams. In this paper, we review the design of high-precision beams, their current limitations, and the latest techniques envisaged to overcome such limits. We put emphasis on “monitored neutrino beams” and advanced diagnostics to determine the flux and flavor of the neutrinos produced at the source at the per-cent level. We also discuss ab-initio measurements of the neutrino energy–i.e., measurements performed without relying on the event reconstruction at the ν detector–to remove any flux induced bias in the determination of the cross sections.

Our knowledge of neutrino cross sections at the GeV scale, instrumental to test CP symmetry violation in the leptonic sector, has grown substantially in the last two decades. Still, their precision and understanding are far from the standard needed in contemporary neutrino physics. Nowadays, the knowledge of the neutrino cross section at O(10%) causes the main systematic uncertainty in oscillation experiments and jeopardizes their physics reach. In this paper, we envision the opportunities for a new generation of cross section experiments to be run in parallel with DUNE and HyperKamiokande. We identify the most prominent physics goals by looking at the theory and experimental limitations of the previous generation of experiments. We highlight the priorities in the theoretical understanding of GeV cross sections and the experimental challenges of this new generation of facilities.

The main source of systematic uncertainty on neutrino cross section measurements at the GeV scale is represented by the poor knowledge of the initial flux. The goal of cutting down this uncertainty to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos, by properly instrumenting the decay region of a conventional narrow-band neutrino beam. Large angle muons and positrons from kaons are measured by a sampling calorimeter on the decay tunnel walls (tagger), while muon stations after the hadron dump can be used to monitor the neutrino component from pion decays. This instrumentation can provide a full control on both the muon and electron neutrino fluxes at all energies. Furthermore, the narrow momentum width (<10%) of the beam provides a O(10%) measurement of the neutrino energy on an event by event basis, thanks to its correlation with the radial position of the interaction at the neutrino detector. The ENUBET project has been funded by the ERC in 2016 to prove the feasibility of such a monitored neutrino beam and is cast in the framework of the CERN neutrino platform (NP06) and the Physics Beyond Colliders initiative. In our contribution, we summarize the ENUBET design, physics performance and opportunities for its implementation in a timescale comparable with next long baseline neutrino experiments.

The OPERA experiment, whose aim is the direct observation of nu_mu ~> nu_tau oscillations in appearance mode in the CNGS high-energy neutrino beam, consists of a high-granularity modular target of nuclear emulsions-lead \"bricks\", richly instrumented with electronic detectors necessary for the location of neutrino interactions and kinematic analysis. After the first short runs of August 2006, October 2006 and October 2007, the experiment started early this summer its first long physics run (about 150 days). Operating at the final target mass of 1.35 kton, the 2008 run can realistically offer the first chance to observe a tau originated from a flavour oscillated nu_mu. This contribution will discuss the different aspects of the experiment, the challenges of the data handling and the recent achievements. It will also outline the various steps required for the analysis in nuclear emulsions from the \"brick finding\" to the vertex reconstruction.

Neutrino physics is nowadays receiving more and more attention as a possible source of information for the long standing problem of new Physics beyond the Standard Model. The recent measurements of the third mixing angle \\(\\theta_{13}\\) in the standard mixing oscillation scenario encourage to pursue the still missing results on the leptonic CP violation and the absolute neutrino masses. However, several puzzling and incomplete measurements are in place which deserve an exhaustive evaluation and study. We will report about the present situation of the muon disappearance measurements at small \\(L/E\\) in the context of the current CERN project to revitalize the neutrino field in Europe and the search for sterile neutrinos. We will then illustrate the achievements that a double muon spectrometer can attain in terms of discovery of new neutrino states, performing a newly developed analysis.

With the discovery of non-zero value of \\(\\theta_{13}\\) mixing angle, the next generation of long-baseline neutrino (LBN) experiments offers the possibility of obtaining statistically significant samples of muon and electron neutrinos and anti-neutrinos with large oscillation effects. In this document we intend to highlight the importance of Near Detector facilities in LBN experiments to both constrain the systematic uncertainties affecting oscillation analyses but also to perform, thanks to their close location, measurements of broad benefit for LBN physics goals. A strong European contribution to these efforts is possible.

A selection of topics on open heavy quark production at HERA are reviewed here. Measurements of charm fragmentation parameters will be presented together with developments in the study of D* di-jet angular distributions. Charm production in deep inelastic scattering (DIS) is also discussed. Finally we deal with recent measurements of b cross sections using impact parameters in both DIS and photoproduction regimes.

Background Emissions from diesel vehicles and biomass burning are the principal sources of primary ultrafine particles (UFP). The exposure to UFP has been associated to cardiovascular and pulmonary diseases, including lung cancer. Although many aspects of the toxicology of ambient particulate matter (PM) have been unraveled, the molecular mechanisms activated in human cells by the exposure to UFP are still poorly understood. Here, we present an RNA-seq time-course experiment (five time point after single dose exposure) used to investigate the differential and temporal changes induced in the gene expression of human bronchial epithelial cells (BEAS-2B) by the exposure to UFP generated from diesel and biomass combustion. A combination of different bioinformatics tools (EdgeR, next-maSigPro and reactome FI app-Cytoscape and prioritization strategies) facilitated the analyses the temporal transcriptional pattern, functional gene set enrichment and gene networks related to cellular response to UFP particles. Results The bioinformatics analysis of transcriptional data reveals that the two different UFP induce, since the earliest time points, different transcriptional dynamics resulting in the activation of specific genes. The functional enrichment of differentially expressed genes indicates that the exposure to diesel UFP induces the activation of genes involved in TNFα signaling via NF-kB and inflammatory response , and hypoxia . Conversely, the exposure to ultrafine particles from biomass determines less distinct modifications of the gene expression profiles. Diesel UFP exposure induces the secretion of biomarkers associated to inflammation ( CCXL2 , EPGN, GREM1 , IL1A , IL1B , IL6 , IL24 , EREG , VEGF ) and transcription factors (as NFE2L2 , MAFF , HES1 , FOSL1 , TGIF1 ) relevant for cardiovascular and lung disease. By means of network reconstruction, four genes ( STAT3 , HIF1 a, NFKB 1, KRAS ) have emerged as major regulators of transcriptional response of bronchial epithelial cells exposed to diesel exhaust. Conclusions Overall, this work highlights modifications of the transcriptional landscape in human bronchial cells exposed to UFP and sheds new lights on possible mechanisms by means of which UFP acts as a carcinogen and harmful factor for human health.

Decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, is tested in combination with conventional anticancer drugs as a treatment option for various solid tumors. Although epigenome modulation provides a promising avenue in treating resistant cancer types, more studies are required to evaluate its safety and ability to normalize the aberrant transcriptional profiles. As deoxycytidine kinase (DCK)-mediated phosphorylation is a rate-limiting step in DAC metabolic activation, we hypothesized that its intracellular overexpression could potentiate DAC’s effect on cell methylome and thus increase its therapeutic efficacy. Therefore, two breast cancer cell lines, JIMT-1 and T-47D, differing in their molecular characteristics, were transfected with a DCK expression vector and exposed to low-dose DAC (approximately IC20). Although transfection resulted in a significant DCK expression increase, further enhanced by DAC exposure, no transfection-induced changes were found at the global DNA methylation level or in cell viability. In parallel, an integrative approach was applied to decipher DAC-induced, methylation-mediated, transcriptomic reprogramming. Besides large-scale hypomethylation, accompanied by up-regulation of gene expression across the entire genome, DAC also induced hypermethylation and down-regulation of numerous genes in both cell lines. Interestingly, TET1 and TET2 expression halved in JIMT-1 cells after DAC exposure, while DNMTs’ changes were not significant. The protein digestion and absorption pathway, containing numerous collagen and solute carrier genes, ranking second among membrane transport proteins, was the top enriched pathway in both cell lines when hypomethylated and up-regulated genes were considered. Moreover, the calcium signaling pathway, playing a significant role in drug resistance, was among the top enriched in JIMT-1 cells. Although low-dose DAC demonstrated its ability to normalize the expression of tumor suppressors, several oncogenes were also up-regulated, a finding, that supports previously raised concerns regarding its broad reprogramming potential. Importantly, our research provides evidence about the involvement of active demethylation in DAC-mediated transcriptional reprogramming.

This paper discusses the use of scripting procedures and structural computation applied to the stonecutting of vaults. Starting from the conceptualization of trumpet squinches in various treatises, it offers an understanding of the parametric framework used. The operation is then replicated on Wallis’s conical edge surface as described by Guarino Guarini, demonstrating how to create complex surfaces from the basic script. The second part concerns the structural behavior of a conical vault in the same coding environment, thanks to Thrust Network Analysis method. Configurative and geometric analysis of vaults is paired with structural integrity in order to better manage historical buildings.