Solving the strongly coupled 2D gravity III: String susceptibility and topological N-point functions

We spell out the derivation of novel features, put forward earlier in a letter, of two dimensional gravity in the strong coupling regime, at $C_L=7$, 13, 19. Within the operator approach previously developed, they neatly follow from the appearence of a new cosmological term/marginal operator, different from the standard weak-coupling one, that determines the world sheet interaction. The corresponding string susceptibility is obtained and found real contrary to the continuation of the KPZ formula. Strongly coupled (topological like) models--only involving zero-mode degrees of freedom--are solved up to sixth order, using the ward identities which follow from the dependence upon the new cosmological constant. They are technically similar to the weakly coupled ones, which reproduce the matrix model results, but gravity and matter quantum numbers are entangled differently.Comment: 21 pages, latex, 10 figure

From Weak to Strong Coupling in Two-Dimensional Gravity

The strong coupling physics of two dimensional gravity at C=7, 13, 19 is deciphered, by building up on previous works along the same line (for a recent review, of the background material, see hep-th/9408069). It is shown that chirality becomes deconfined. The string suceptibility is derived, and found to be real contrary to the continuation of the KPZ formula. Topological Liouville string theories (without transverse degree of freedom) are explicitely solved. Altough they involve strongly coupled gravity, they share many features with the standard matrix models.Comment: LPTENS-94/25, Latex file + figure

Solving the Strongly Coupled 2D Gravity: 2. Fractional-Spin Operators, and Topological Three-Point Functions

Progress along the line of a previous article are reported. One main point is to include chiral operators with fractional quantum group spins (fourth or sixth of integers) which are needed to achieve modular invariance. We extend the study of the chiral bootstrap (recently completed by E. Cremmer, and the present authors) to the case of semi-infinite quantum-group representations which correspond to positive integral screening numbers. In particular, we prove the Bidenharn-Elliot and Racah identities for q-deformed 6-j symbols generalized to continuous spins. The decoupling of the family of physical chiral operators (with real conformal weights) at the special values C_{Liouville}= =7, 13, and 19, is shown to provide a full solution of Moore and Seiberg's equations, only involving operators with real conformal weights. Moreover, our study confirms the existence of the strongly coupled topological models. The three-point functions are shown to be given by a product of leg factors similar to the ones of the weakly coupled models. However, contrary to this latter case, the equality between the quantum group spins of the holomorphic and antiholomorphic components is not preserved by the local vertex operator. Thus the ``c=1'' barrier appears as connected with a deconfinement of chirality.Comment: 45 pages Latex file, 14 figures (uuencoded

De la sécurité de l'État à celle de l'individu: l'évolution du concept de sécurité au Canada (1990-1996)

Les transformations récentes du système international ont obligé les États à revoir les fondements conceptuels de leurs politiques de sécurité. Le cas du Canada est révélateur à cet égard, puisque le gouvernement fut l'un des premiers à proposer une redéfinition de la notion de « sécurité ». Il a ainsi formulé, dès 1990, le concept de « sécurité coopérative » puis, en 1995, celui de « sécurité humaine ». L'objet de ce texte est de démontrer que cette évolution marque une rupture très nette avec le corpus conceptuel employé au cours de la guerre froide. Cette rupture est particulièrement évidente au niveau de la définition de la menace, de l'identification de l'objet de la sécurité et de la gestion des moyens utilisés pour contrer la menace. Par ailleurs, ce virage conceptuel ne semble pas accompagné d'une réflexion en profondeur sur les conséquences qu'il entraîne au niveau de la mise en oeuvre des politiques. Les lacunes qui subsistent expliquent, en grande partie, le manque de cohérence des politiques de sécurité actuelles du Canada.The recent transformations in the international System convinced many States to rethink the conceptual framework of their security policies. Canada is a good example, since the government was among the first to propose a new definition of the notion of "security". In 1990, he proposed the concept of "cooperative security" and, in 1995, the notion of "human security". The aim of this paper is first to show how this evolution represents a definitive rupture with the traditional concept used during the Cold War. This is clearly evident at three levels : definition of the threat, identification of the subject of security, and the instrument used to meet the threat. The paper also indicates that this conceptual evolution was not supported by a clear assessment of the consequences and the problems in the implementation of the policies inspired by a concept such as "human security". These lacks could explain many problems in the actual security policy of Canada

The Quantum Group Structure of 2D Gravity and Minimal Models II: The Genus-Zero Chiral Bootstrap

The F and B matrices associated with Virasoro null vectors are derived in closed form by making use of the operator-approach suggested by the Liouville theory, where the quantum-group symmetry is explicit. It is found that the entries of the fusing and braiding matrices are not simply equal to quantum-group symbols, but involve additional coupling constants whose derivation is one aim of the present work. Our explicit formulae are new, to our knowledge, in spite of the numerous studies of this problem. The relationship between the quantum-group-invariant (of IRF type) and quantum-group-covariant (of vertex type) chiral operator-algebras is fully clarified, and connected with the transition to the shadow world for quantum-group symbols. The corresponding 3-j-symbol dressing is shown to reduce to the simpler transformation of Babelon and one of the author (J.-L. G.) in a suitable infinite limit defined by analytic continuation. The above two types of operators are found to coincide when applied to states with Liouville momenta going to $\infty$ in a suitable way. The introduction of quantum-group-covariant operators in the three dimensional picture gives a generalisation of the quantum-group version of discrete three-dimensional gravity that includes tetrahedra associated with 3-j symbols and universal R-matrix elements. Altogether the present work gives the concrete realization of Moore and Seiberg's scheme that describes the chiral operator-algebra of two-dimensional gravity and minimal models.Comment: 56 pages, 22 figures. Technical problem only, due to the use of an old version of uuencode that produces blank characters some times suppressed by the mailer. Same content

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms.

Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth, and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic, and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multiomics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C