Enregistrement des paramètres ventilatoires par les dispositifs de VNI (un nouvel outil pour la détection précoce d'exacerbation chez des patients BPCO traités au long cours par VNI ?)

Physiological parameters recorded by built-in software of noninvasive ventilation (NIV) devices may exhibit a characteristic pattern leading up to exacerbations in COPD treated by home NIV. To assess whether daily variations in respiratory rate (RR), percentage of respiratory cycles triggered by the patient (%Trigg) and NIV daily use allow early detection of exacerbation. NIV parameters were collected and analyzed from COPD patients treated by long term NIV. Over a period of 6 months, patients completed the EXACT-Pro questionnaire daily. 25th and 75th percentiles of each 24-hour parameter recorded by the ventilator (RR, %Trigg, daily use) were calculated from the fourth day of follow-up and updated daily. For a given day, when the value of a parameter was > 75th or 75th, Low-Value 75ème ou 75ème, valeur basse <25ème). Des modèles de régression logistique stratifiés ont été utilisés pour estimer le risque d exacerbation lorsque 2 jours ou plus (pour FR, %cycles) ou 3 jours ou plus (pour la VNI) sur 5 étaient étiquetés valeurs anormales . 64 patients ont été inclus (moyenne d âge 71 ans, VEMS=31,2% valeur prédite, IMC=27,2kg/m-2, CAT score=18). 21 exacerbations ont été détectées avec EXACT-pro et confirmées par un comité d experts. Le risque d exacerbation était augmenté lorsque la FR (OR=5.6 [1.4;22.4]) et le %cycles (OR=4.0 [1.1;14.5]) étaient considérés comme valeur haute 2 jours ou plus sur 5 jours. Les paramètres enregistrés par les logiciels de VNI peuvent être outil innovant outil pour détecter les exacerbations.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Dipole Antenna Printed on Paper Substrate for WLAN Applications

International audienceThe design of a dipole antenna printed on a paper substrate is presented in this paper. The antenna which integrates a compact balun is devoted for dual-band 2.4/5 GHz WLAN applications. The antenna is based on a double-side printed multilayer paper substrate and is fed with a coaxial cable for the testing. The simulated results of the whole structure are also presented in detail and compared with the measured performances

Twisting algebras using non-commutative torsors

Non-commutative torsors (equivalently, two-cocycles) for a Hopf algebra can be used to twist comodule algebras. After surveying and extending the literature on the subject, we prove a theorem that affords a presentation by generators and relations for the algebras obtained by such twisting. We give a number of examples, including new constructions of the quantum affine spaces and the quantum tori.Comment: 27 pages. Masuoka is a new coauthor. Introduction was revised. Sections 1 and 2 were thoroughly restructured. The presentation theorem in Section 3 is now put in a more general framework and has a more general formulation. Section 4 was shortened. All examples (quantum affine spaces and tori, twisting of SL(2), twisting of the enveloping algebra of sl(2)) are left unchange

Pseudoconvex domains spread over complex homogeneous manifolds

Using the concept of inner integral curves defined by Hirschowitz we generalize a recent result by Kim, Levenberg and Yamaguchi concerning the obstruction of a pseudoconvex domain spread over a complex homogeneous manifold to be Stein. This is then applied to study the holomorphic reduction of pseudoconvex complex homogeneous manifolds X=G/H. Under the assumption that G is solvable or reductive we prove that X is the total space of a G-equivariant holomorphic fiber bundle over a Stein manifold such that all holomorphic functions on the fiber are constant.Comment: 21 page

Safe and Efficient Silencing with a Pol II, but not a Pol lII, Promoter Expressing an Artificial miRNA Targeting Human Huntingtin

Huntington\u27s disease is a devastating, incurable neurodegenerative disease affecting up to 12 per 100,000 patients worldwide. The disease is caused by a mutation in the Huntingtin (Htt) gene. There is interest in reducing mutant Huntingtin by targeting it at the mRNA level, but the maximum tolerable dose and long-term effects of such a treatment are unknown. Using a self-complementary AAV9 vector, we delivered a mir-155-based artificial miRNA under the control of the chicken β-actin or human U6 promoter. In mouse brain, the artificial miRNA reduced the human huntingtin mRNA by 50%. The U6, but not the CβA promoter, produced the artificial miRNA at supraphysiologic levels. Embedding the antisense strand in a U6-mir-30 scaffold reduced expression of the antisense strand but increased the sense strand. In mice treated with scAAV9-U6-mir-155-HTT or scAAV9-CβA-mir-155-HTT, activated microglia were present around the injection site 1 month post-injection. Six months post-injection, mice treated with scAAV9-CβA-mir-155-HTT were indistinguishable from controls. Those that received scAAV9-U6-mir-155-HTT showed behavioral abnormalities and striatal damage. In conclusion, miRNA backbone and promoter can be used together to modulate expression levels and strand selection of artificial miRNAs, and in brain, the CβA promoter can provide an effective and safe dose of a human huntingtin miRNA

Sturmian morphisms, the braid group B_4, Christoffel words and bases of F_2

We give a presentation by generators and relations of a certain monoid generating a subgroup of index two in the group Aut(F_2) of automorphisms of the rank two free group F_2 and show that it can be realized as a monoid in the group B_4 of braids on four strings. In the second part we use Christoffel words to construct an explicit basis of F_2 lifting any given basis of the free abelian group Z^2. We further give an algorithm allowing to decide whether two elements of F_2 form a basis or not. We also show that, under suitable conditions, a basis has a unique conjugate consisting of two palindromes.Comment: 25 pages, 4 figure

Therapeutic rAAVrh10 Mediated SOD1 Silencing in Adult SOD1(G93A) Mice and Nonhuman Primates

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; survival in ALS is typically 3-5 years. No treatment extends patient survival by more than three months. Approximately 20% of familial ALS and 1-3% of sporadic ALS patients carry a mutation in the gene encoding superoxide dismutase 1 (SOD1). In a transgenic ALS mouse model expressing the mutant SOD1(G93A) protein, silencing the SOD1 gene prolongs survival. One study reports a therapeutic effect of silencing the SOD1 gene in systemically treated adult ALS mice; this was achieved with a short hairpin RNA, a silencing molecule that has raised multiple safety concerns, and recombinant adeno-associated virus (rAAV) 9. We report here a silencing method based on an artificial microRNA termed miR-SOD1 systemically delivered using adeno-associated virus rAAVrh10, a serotype with a demonstrated safety profile in CNS clinical trials. Silencing of SOD1 in adult SOD1(G93A) transgenic mice with this construct profoundly delayed both disease onset and death in the SOD1(G93A) mice, and significantly preserved muscle strength and motor and respiratory functions. We also document that intrathecal delivery of the same rAAVrh10-miR-SOD1 in nonhuman primates significantly and safely silences SOD1 in lower motor neurons. This study supports the view that rAAVrh10-miR-SOD1 merits further development for the treatment of SOD1-linked ALS in humans

Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited Hepatocytes for Treatment of alpha-1 Antitrypsin Deficiency

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create a recipient strain (NSG-PiZ) for human hepatocyte xenotransplantation. Results indicate that NSG-PiZ recipients support heightened engraftment of normal human primary hepatocytes as compared with NSG recipients. This model can therefore be used to test hepatocyte cell therapies for AATD, but more broadly it serves as a simple, highly reproducible liver xenograft model. Finally, a promoterless adeno-associated virus (AAV) vector, expressing a wild-type AAT and a synthetic miRNA to silence the endogenous allele, was integrated into the albumin locus. This gene-editing approach leads to a selective advantage of edited hepatocytes, by silencing the mutant protein and augmenting normal AAT production, and improvement of the liver pathology

Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited Hepatocytes for Treatment of α-1 Antitrypsin Deficiency.

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In α-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create a recipient strain (NSG-PiZ) for human hepatocyte xenotransplantation. Results indicate that NSG-PiZ recipients support heightened engraftment of normal human primary hepatocytes as compared with NSG recipients. This model can therefore be used to test hepatocyte cell therapies for AATD, but more broadly it serves as a simple, highly reproducible liver xenograft model. Finally, a promoterless adeno-associated virus (AAV) vector, expressing a wild-type AAT and a synthetic miRNA to silence the endogenous allele, was integrated into the albumin locus. This gene-editing approach leads to a selective advantage of edited hepatocytes, by silencing the mutant protein and augmenting normal AAT production, and improvement of the liver pathology. Mol Ther 2017 Nov 1; 25(11):2477-2489