MiniBooNE Results and Neutrino Schemes with 2 sterile Neutrinos: Possible Mass Orderings and Observables related to Neutrino Masses

The MiniBooNE and LSND experiments are compatible with each other when two sterile neutrinos are added to the three active ones. In this case there are eight possible mass orderings. In two of them both sterile neutrinos are heavier than the three active ones. In the next two scenarios both sterile neutrinos are lighter than the three active ones. The remaining four scenarios have one sterile neutrino heavier and another lighter than the three active ones. We analyze all scenarios with respect to their predictions for mass-related observables. These are the sum of neutrino masses as constrained by cosmological observations, the kinematic mass parameter as measurable in the KATRIN experiment, and the effective mass governing neutrinoless double beta decay. It is investigated how these non-oscillation probes can distinguish between the eight scenarios. Six of the eight possible mass orderings predict positive signals in the KATRIN and future neutrinoless double beta decay experiments. We also remark on scenarios with three sterile neutrinos. In addition we make some comments on the possibility of using decays of high energy astrophysical neutrinos to discriminate between the mass orderings in presence of two sterile neutrinos.Comment: 33 pages, 8 figures. Comments added, to appear in JHE

Perturbative Matching of the staggered four-fermion operators for e'/e

Using staggered fermions, we calculate the perturbative corrections to the bilinear and four-fermion operators that are used in the numerical study of weak matrix elements for $\epsilon'/\epsilon$. We present results for one-loop matching coefficients between continuum operators, calculated in the Naive Dimensional Regularization (NDR) scheme, and gauge invariant staggered fermion operators. These results, combined with existing results for penguin diagrams, provide the complete one-loop renormalization of the staggered four-fermion operators.Comment: 36 pages. will appear in physical review

Inclusion into PLGA nanoparticles greatly improves the effectiveness of \u3b1-bisabolol to inhibit human Dendritic Cell pro-inflammatory activity

a-bisabolol, a natural sesquiterpene alcohol, has generated considerable interest for its antiinflammatory activity. Since the mechanisms of this anti-inflammatory action remain poorly understood, we investigated whether a-bisabolol affects the release of pro-inflammatory cytokines IL-12, IL-23, IL-6, and TNFa by human dendritic cells (DCs). We found that a-bisabolol did not induce the secretion of these cytokines and did not affect their release induced upon DC challenge with lipopolysaccharide (LPS), a well-known immune cell stimulator. As a-bisabolol is scarcely ingested by the cells, we wondered hether the inclusion of a-bisabolol into nanoparticles could favor its internalization by DCs and consequently its effects on cytokine secretion. We then prepared and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, with a dynamic light scattering peak centered at 154 nm and a half width at half maximum of about 48 nm. These particles were unable to affect per se cytokine secretion by both resting and LPS stimulated DCs and were internalized by human DCs as demonstrated by confocal microscopy analysis. We then loaded PLGA nanoparticles with a-bisabolol and we observed that PLGA-associated a-bisabolol did not stimulate the cytokine release by resting DCs, but decreased IL-12, IL-23, IL-6, and TNFa secretion by LPS-stimulated DCs. Our results indicate that abisabolol inclusion into PLGA anoparticles represents a very promising tool for designing new antiinflammatory, anti-pyretic and, possibly, immunosuppressive therapeutic strategie

Super Yang-Mills on the lattice with domain wall fermions

The dynamical N=1, SU(2) Super Yang-Mills theory is studied on the lattice using a new lattice fermion regulator, domain wall fermions. This formulation even at non-zero lattice spacing does not require fine-tuning, has improved chiral properties and can produce topological zero-mode phenomena. Numerical simulations of the full theory on lattices with the topology of a torus indicate the formation of a gluino condensate which is sustained at the chiral limit. The condensate is non-zero even for small volume and small supersymmetry breaking mass where zero mode effects due to gauge fields with fractional topological charge appear to play a role.Comment: LaTeX, 35 pages, 11 eps figures. A few changes in sec. 5.3, figure 11 added. To appear in Phys. Rev.

CD44v6 as innovative sarcoma target for CAR-redirected CIK cells

Purpose of our study was to explore a new immunotherapy for high grade soft tissue sarcomas (STS) based on cytokine-induced killer cells (CIK) redirected with a chimeric antigen receptor (CAR) against the tumor-promoting antigen CD44v6. We aimed at generating bipotential killers, combining the CAR specificity with the intrinsic tumor-killing ability of CIK cells (CAR+.CIK). We set a patient-derived experimental platform. CAR+.CIK were generated by transduction of CIK precursors with a lentiviral vector encoding for anti-CD44v6-CAR. CAR+.CIK were characterized and assessed in vitro against multiple histotypes of patient-derived STS. The anti-sarcoma activity of CAR+.CIK was confirmed in a STS xenograft model. CD44v6 was expressed by 40% (11/27) of patient-derived STS. CAR+.CIK were efficiently expanded from patients (n = 12) and killed multiple histotypes of STS (including autologous targets, n = 4). The killing activity was significantly higher compared with unmodified CIK, especially at low effector/target (E/T) ratios: 98% vs 82% (E/T = 10:1) and 68% vs 26% (1:4), (p<0.0001). Specificity of tumor killing was confirmed by blocking with anti-CD44v6 antibody. CAR+.CIK produced higher amounts of IL6 and IFN-γ compared to control CIK. CAR+.CIK were highly active in mice bearing subcutaneous STS xenografts, with significant delay of tumor growth (p<0.0001) without toxicities. We report first evidence of CAR+.CIK's activity against high grade STS and propose CD44v6 as an innovative target in this setting. CIK are a valuable platform for the translation of CAR-based strategies to challenging field of solid tumors. Our findings support the exploration of CAR+.CIK in clinical trials against high grade STS

Concentration-QT modelling of the novel DHFR inhibitor P218 in healthy male volunteers.

AIMS: Given the increasing emergence of drug resistance in Plasmodium, new antimalarials are urgently required. P218 is an aminopyridine that inhibits dihydrofolate reductase being developed as a malaria chemoprotective drug. Assessing the effect of new compounds on cardiac intervals is key during early drug development to determine their cardiac safety. METHODS: This double-blind, randomized, placebo-controlled, parallel group study evaluated the effect of P218 on electrocardiographic parameters following oral administration of seven single-ascending doses up to 1000 mg in 56 healthy volunteers. Participants were randomized to treatment or placebo at a 3:1 ratio. P218 was administered in the fasted state with standardized lunch served 4 hours after dosing. 12-lead ECGs were recorded in triplicate at regular intervals on the test day, and at 48, 72, 120, 168, 192 and 240 hours thereafter. Blood samples for pharmacokinetic evaluations were collected at similar time points. Concentration-effect modelling was used to assess the effect of P218 and its metabolites on cardiac intervals. RESULTS: Concentration-effect analysis showed that P218 does not prolong the QTcF, J-Tpeak or TpTe interval at all doses tested. No significant changes in QRS or PR intervals were observed. Two-sided 90% confidence intervals of subinterval effects of P218 and its metabolites were consistently below the regulatory concern threshold for all doses. Study sensitivity was confirmed by significant shortening of QTcF after a meal. CONCLUSION: Oral administration of P218 up to 1000 mg does not prolong QTcF and does not significantly change QRS or PR intervals, suggesting low risk for drug-induced proarrhythmia

Safety and clinical outcomes of abiraterone acetate (aa) after docetaxel (doc) in octogenarians with metastatic castration-resistant prostate cancer (mcrpc)

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