On the Optimum Long Baseline for the Next Generation Neutrino Oscillation Experiments

For high energy long baseline neutrino oscillation experiments, we propose a Figure of Merit criterion to compare the statistical quality of experiments at various oscillation distances under the condition of identical detectors and a given neutrino beam. We take into account all possible experimental errors under general consideration. In this way the Figure of Merit is closely related to the usual statistical criterion of number of sigmas. We use a realistic neutrino beam for an entry level neutrino factory and a possible superbeam from a meson source and a 100 kt detector for the calculation. We considered in detail four oscillation distances, 300 km, 700 km, 2100 km and 3000 km, in the neutrino energy range of 0.5-20 GeV for a 20 GeV entry level neutrino factory and a 50 GeV superbeam. We found that the very long baselines of 2100 km and 3000 km are preferred for the neutrino factory according to the figure of merit criterion. Our results also show that, for a neutrino factory, lower primary muon energies such as 20 GeV are preferred rather than higher ones such as 30 or 50 GeV. For the superbeam, the combination of a long baseline such as 300 km and a very long baseline like 2100 km will form a complete measurement of the oscillation parameters besides the CP phase. To measure the CP phase in a superbeam, a larger detector (a factor 3 beyond what is considered in this article) and/or a higher intensity beam will be needed to put some significant constraints on the size of the CP angle.Comment: 21 LaTeX pages, 13 PS figures, typos corrected, references adde

The changes of immunoglobulin G N-glycosylation in blood lipids and dyslipidaemia

Background Alternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension. Methods Herein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20–68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography. Results Blood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P \u3c 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P \u3c 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644–0.740). Conclusions Our findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia

Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)

IntroductionSafranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity.Methods and resultsHere, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ.ConclusionThis study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ

Discrete element simulation and experimental study of powder spreading process in additive manufacturing

Powders used in additive manufacturing (AM) are spread into a compact layer of particles for sintering and this process is repeated layer by layer to form the final products. Spreading of rod-shaped particles in realistic AM settings is simulated using the discrete element method (DEM) to investigate the effects of particle shape and operating conditions on the bed quality, characterised by its surface roughness and solid volume fraction. It is discovered that larger particle aspect ratios, Ar, or higher spreader translational velocities result in a lower bed quality, i.e. a larger surface roughness and a smaller volume fraction. The surface roughness increases monotonically with Ar. However, the volume fraction exhibits a maximum at Ar = 1.5 for randomly packed powder beds that are formed by the roller type spreaders moving at low translational velocities. It is also found that a roller outperforms a blade spreader in terms of the quality of the prepared bed at the same operating conditions. The micro-structural analysis of the beds also shows particle alignment in response to the induced flow, which is qualitatively confirmed by a set of purposely-designed experiments. In addition, a shape segregation is documented for powders with mixed aspect ratios (Ar) such that particles with larger Ar tend to accumulate on the upper layers of the bed

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Increased origin activity in transformed versus normal cells: identification of novel protein players involved in DNA replication and cellular transformation

Using libraries of replication origins generated previously, we identified three clones that supported the autonomous replication of their respective plasmids in transformed, but not in normal cells. Assessment of their in vivo replication activity by in situ chromosomal DNA replication assays revealed that the chromosomal loci corresponding to these clones coincided with chromosomal replication origins in all cell lines, which were more active by 2–3-fold in the transformed by comparison to the normal cells. Evaluation of pre-replication complex (pre-RC) protein abundance at these origins in transformed and normal cells by chromatin immunoprecipitation assays, using anti-ORC2, -cdc6 and -cdt1 antibodies, showed that they were bound by these pre-RC proteins in all cell lines, but a 2–3-fold higher abundance was observed in the transformed by comparison to the normal cells. Electrophoretic mobility shift assays (EMSAs) performed on the most efficiently replicating clone, using nuclear extracts from the transformed and normal cells, revealed the presence of a DNA replication complex in transformed cells, which was barely detectable in normal cells. Subsequent supershift EMSAs suggested the presence of transformation-specific complexes. Mass spectrometric analysis of these complexes revealed potential new protein players involved in DNA replication that appear to correlate with cellular transformation