Do stochastic inhomogeneities affect dark-energy precision measurements?

The effect of a stochastic background of cosmological perturbations on the luminosity-redshift relation is computed to second order through a recently proposed covariant and gauge-invariant light-cone averaging procedure. The resulting expressions are free from both ultraviolet and infrared divergences, implying that such perturbations cannot mimic a sizable fraction of dark energy. Different averages are estimated and depend on the particular function of the luminosity distance being averaged. The energy flux being minimally affected by perturbations at large z is proposed as the best choice for precision estimates of dark-energy parameters. Nonetheless, its irreducible (stochastic) variance induces statistical errors on Ω(Λ)(z) typically lying in the few-percent range.

Backreaction during inflation: a physical gauge invariant formulation.

Within a genuinely gauge invariant approach recently developed for the computation of the cosmological backreaction, we study, in a cosmological inflationary context and with respect to various observers, the impact of scalar fluctuations on the space-time dynamics in the long wavelength limit. We stress that such a quantum backreaction effect is evaluated in a truly gauge independent way using a set of effective equations which describe the dynamics of the averaged geometry. In particular we show under what conditions the free falling (geodetic) observers do not experience any scalar-induced backreaction in the effective Hubble rate and fluid equation of state.

Early-onset Type II diabetes mellitus in Italian families due to mutations in the genes encoding hepatic nuclear factor 1 alpha and glucokinase.

AIMS/HYPOTHESIS: Maturity-onset-diabetes of the young (MODY) is caused by mutations in at least five different genes. Our aim was to determine the prevalence of the most common MODY genes in Italian families with early-onset Type II (non-insulin-dependent) diabetes mellitus. METHODS: We screened 28 Italian early-onset Type II diabetic families (diagnosis < 35 years) for mutations in the hepatic nuclear factor-4 alpha, (MODY1), glucokinase (MODY2) and hepatic nuclear factor-1 alpha (MODY3). Both strands of exons, flanking introns and minimal promoter regions of the above-mentioned genes were amplified using polymerase chain reaction and were sequenced directly. RESULTS: We identified four different mutations, three of which are not described, (W113X, G42P43fsCC --> A, H514R) and four new polymorphisms (G184G, T513T, IVS3-nt47delG, IVS1- nt53C --> G) in the hepatic nuclear factor-1 alpha gene, two new potential mutations (G44S, IVS4nt + 7C --> T) and three new polymorphisms (promoter-nt84C --> G, IVS9 + nt8C --> T, IVS9 + nt49G --> A) in the glucokinase gene, and a new polymorphism (IVS1c-nt11T --> G) in the hepatic nuclear factor-4 alpha gene. CONCLUSION/INTERPRETATION: Mutations in the hepatic nuclear factor-1 alpha and glucokinase are associated with Type II diabetes in 14 % and 7 % of Italian families, respectively. Our findings provide an impetus for screening Italian MODY and early-non Type II diabetic families for mutations in the above mentioned genes to identify relatives at risk who could benefit from primary prevention care. [

Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4 alpha binding site in the promoter of the hepatocyte nuclear factor-1 alpha gene.

Recent studies have shown that mutations in the transcription factor hepatocyte nuclear factor (HNF)-1 alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). These studies have identified mutations in the mRNA and protein coding regions of this gene that result in the synthesis of an abnormal mRNA or protein. Here, we report an Italian family in which an A-->C substitution at nucleotide-58 of the promoter region of the HNF-1 alpha gene cosegregates with MODY. This mutation is located in a highly conserved region of the promoter and disrupts the binding site for the transcription factor HNF-4 alpha, mutations in the gene encoding HNF-4 alpha being another cause of MODY (MODY1). This result demonstrates that decreased levels of HNF-1 alpha per se can cause MODY. Moreover, it indicates that both the promoter and coding regions of the HNF-1 alpha gene should be screened for mutations in subjects thought to have MODY because of mutations in this gene.