Sapienza University of Rome

About: Sapienza University of Rome is a education organization based out in Rome, Lazio, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 62002 authors who have published 155468 publications receiving 4397244 citations. The organization is also known as: La Sapienza & Università La Sapienza di Roma.

Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells

Abstract: Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the α(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for α(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.

Domain Generalization by Solving Jigsaw Puzzles

Abstract: Human adaptability relies crucially on the ability to learn and merge knowledge both from supervised and unsupervised learning: the parents point out few important concepts, but then the children fill in the gaps on their own. This is particularly effective, because supervised learning can never be exhaustive and thus learning autonomously allows to discover invariances and regularities that help to generalize. In this paper we propose to apply a similar approach to the task of object recognition across domains: our model learns the semantic labels in a supervised fashion, and broadens its understanding of the data by learning from self-supervised signals how to solve a jigsaw puzzle on the same images. This secondary task helps the network to learn the concepts of spatial correlation while acting as a regularizer for the classification task. Multiple experiments on the PACS, VLCS, Office-Home and digits datasets confirm our intuition and show that this simple method outperforms previous domain generalization and adaptation solutions. An ablation study further illustrates the inner workings of our approach.

Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection

Abstract: methods We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks’ gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously). results In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, i ∞ to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects. conclusions Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.

Measurement of neutrino oscillation by the K2K experiment

Abstract: We present measurements of {nu}{sub {mu}} disappearance in K2K, the KEK to Kamioka long-baseline neutrino oscillation experiment. One-hundred and twelve beam-originated neutrino events are observed in the fiducial volume of Super-Kamiokande with an expectation of 158.1{sub -8.6}{sup +9.2} events without oscillation. A distortion of the energy spectrum is also seen in 58 single-ring muonlike events with reconstructed energies. The probability that the observations are explained by the expectation for no neutrino oscillation is 0.0015% (4.3{sigma}). In a two-flavor oscillation scenario, the allowed {delta}m{sup 2} region at sin{sup 2}2{theta}=1 is between 1.9 and 3.5x10{sup -3} eV{sup 2} at the 90% C.L. with a best-fit value of 2.8x10{sup -3} eV{sup 2}.