Many-body aspects of positron annihilation in the electron gas

We investigate positron annihilation in electron liquid as a case study for many-body theory, in particular the optimized Fermi Hypernetted Chain (FHNC-EL) method. We examine several approximation schemes and show that one has to go up to the most sophisticated implementation of the theory available at the moment in order to get annihilation rates that agree reasonably well with experimental data. Even though there is basically just one number to look at, the electron-positron pair distribution function at zero distance, it is exactly this number that dictates how the full pair distribution behaves: In most cases, it falls off monotonously towards unity as the distance increases. Cases where the electron-positron pair distribution exhibits a dip are precursors to the formation of bound electron--positron pairs. The formation of electron-positron pairs is indicated by a divergence of the FHNC-EL equations, from this we can estimate the density regime where positrons must be localized. This occurs in our calculations in the range 9.4 <= r_s <=10, where r_s is the dimensionless density parameter of the electron liquid.Comment: To appear in Phys. Rev. B (2003

A novel treatment of cystic fibrosis acting on-target:cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment