Squashed Holography with Scalar Condensates

We evaluate the partition function of the free and interacting O(N) vector model on a two-parameter family of squashed three spheres in the presence of a scalar deformation. We also find everywhere regular solutions of Einstein gravity coupled to a scalar field in AdS and in dS with the same double squashed boundary geometry. Remarkably, the thermodynamic properties of the AdS solutions qualitatively agree with the behavior predicted by the free O(N) model with a real mass deformation. The dS bulk solutions specify the semiclassical `no-boundary' measure over anisotropic deformations of inflationary, asymptotic de Sitter space. Through dS/CFT the partition function of the interacting O(N) model yields a holographic toy model of the no-boundary measure. We find this yields a qualitatively similar probability distribution which is normalizable and globally peaked at the round three sphere, with a low amplitude for strong anisotropies.Comment: 35 pages, version 2: presentation changed and comments adde

Aspetti problematici del processo di elezione del Presidente degli Stati Uniti

L'Autore affronta alcune problematiche di carattere costituzionale e politico relative al processo di elezione del Presidente degli Stati Uniti, analizzando il sistema delle primarie, il criterio di selezione dei cosiddetti Grandi Elettori e il modello del Collegio Elettorale

Il Super Tuesday del 2016. La voce del Sud alle primarie presidenziali degli Stati Uniti

Il Super Tuesday del 2016. La voce del Sud alle primarie presidenziali degli Stati Unit

I caucuses dello Iowa del 2016 e la corsa alle nomination del Partito democratico e del Partito repubblicano statunitensi

Osservatorio CostituzionaleThis article provides an analysis of the results of the 2016 Iowa’s Democratic and Republican presidential caucuses. The Iowa caucus represents the first electoral event in the presidential nomination process for both Democratic Party and Republican Party since 1972 and 1976 respectively. The Author examines the two party’s delegate selection systems adopted for the 2016 caucuses in the Midwestern State, and offers an overview of the 2016 presidential candidates

L'evoluzione dell'istituto dello state of the union address e la carica progressista nell'ultimo biennio del secondo mandato Obama

L'articolo mette in luce le varie fasi di trasformazione della forma di governo statunitense, a partire dalla presidenza Washington sino alla seconda metà del secondo mandato Obama, utilizzando quale parametro l'evoluzione dello "stato dell'unione", istituto del quale si analizzano i profili costituzionali e l'impatto sul piano politico-istituzionale

Il momentum dei candidati anti-establishment alle primarie presidenziali del New Hampshire del 2016

Il momentum dei candidati anti-establishment alle primarie presidenziali del New Hampshire del 2016This article provides an analysis of the 2016 New Hampshire Democratic and Republican presidential primaries. The Author examines the role of New Hampshire in the presidential nomination process and arrives at the following conclusions. On the one hand, New Hampshire's ability to determine who win the nomination have weakened in the last two decades while on the other hand, the progressive shortening of the primary season increased the possibility for an underdog candidate winning or performing better-than-expected in New Hampshire to ride momentum to the nomination

Le elezioni presidenziali e congressuali statunitensi del 2016 tra polarizzazione e party reconstruction

Le elezioni presidenziali e congressuali statunitensi del 2016 tra polarizzazione e party reconstructionDonald Trump won the 2016 U.S. Presidential election, thus becoming the 45th President of the United States. The real-estate tycoon from New York defeated Hillary Clinton, the first woman to be nominated as the presidential candidate of a major U.S. political party, while the Republican Party maintained the majority in both chambers of the U.S. Congress. In this sense, the GOP achieved the so-called “government trifecta”, gaining control of both Executive and Legislative branch at the federal level. Clinton won the popular vote, but lost the Electoral College, thus becoming the second candidate in modern U.S. history to experience that outcome after Al Gore in 2000. In this article, we will provide a preliminary analysis of the results of the 2016 presidential and congressional elections, and we will examine as well the process of electing the President and Vice-President of the United States, focusing on the Electoral College system and its impact on contemporary American politics

Filibuster e nuclear optional Senato USA. L’effetto domino della nomina di Neil Gorsuch alla Corte Suprema degli Stati Uniti

L’eredità di Antonin Scalia. Gli equilibri nella Corte Suprema e l’opposizione repubblicana contro la nomina di Merrick Garland. L’aggiornamento delle procedure del Senato attraverso la “nuclear option” per la nomina di Neil Gorsuch. I risvolti costituzionalistici della nuclear option adottata dai Repubblican

Synthesis of glycomimetics of the natural Siglec-8 ligand and their pharmacodynamic characterization

Glycans are an important class of natural products, since all living cells are covered by different types of carbohydrates forming the glycocalyx. Therefore, any cell-cell recognition process is based on the ability of one cell to recognize the specific glycan pattern which is presented on the other cell surface. This is particularly important for the activation of the immune system, which needs to selectively recognize and kill invading pathogens while not damaging self cells. However, sometimes this delicate equilibrium shifts towards unwanted pathological conditions where the immune system is not able anymore to distinguish between self and non-self cells, causing autoimmune diseases. Additionally, undesired overexpression of immune cells can also lead to medical conditions, like allergic inflammation. Therefore, it is fundamental to rely on specific mechanisms to control immune system homeostasis and avoid abnormal up-regulation of these cells. For this reason, immune cells display inhibitory receptors which suppress their activation via different mechanisms, such as inducing cell death. One type of inhibitory proteins expressed on immune cells are siglecs, a class of I-type transmembrane proteins which selectively recognize sialic acid-containing structures. Siglecs possess multifarious functions, according to the structure and cell type expressing them, but the majority of them acts as inhibitory receptor thanks to the presence of ITIM and ITIM-like motifs in their intracellular domain. One member of this family is Siglec-8, which is expressed only on eosinophils, mast cells, and to some extent on basophils. It exerts its inhibitory function by promoting eosinophils apoptosis and inhibition of mast cells degranulation, representing therefore an interesting pharmacological target for the treatment of diseases in which these cell types are overexpressed, among which asthma and allergic inflammations. This thesis describes a medicinal chemistry approach for the development of high-affinity Siglec-8 ligands to identify potential drug candidates for the treatment of eosinophil- and mast cell-associated diseases. This drug discovery process started from the known structure of the preferred natural Siglec-8 ligand identified via a glycan array approach, the tetrasaccharide 6’-sulfo-sialyl Lewisx (6’-sulfo-sLex). The complex chemical structure of this compound neither allows an easy and straightforward synthesis of derivatives, nor do its chemical properties meet the requirements for drug-like molecules. First, the minimal binding epitope of 6’-sulfo-sLex was identified in the corresponding Neu5Ac-α2-3-Gal6S disaccharide. Although it has a simplified chemical structure, the affinity was reduced only by a factor 2 (Paper 1). In-depth analysis of the pharmacophores, with the aid of computational studies, allowed the development of a glycomimetic analogue, where the galactose moiety was replaced by a carbocyclic structure. Affinity was improved thanks to a reduced desolvation penalty by removing non-interacting hydroxyl groups. When finally the C-9 hydroxyl group of the sialic acid was transferred into an aromatic sulfonamide, affinity was further improved almost 20-fold. Generally, carbohydrate-binding proteins are characterized by weak affinities in the low millimolar range towards their ligands due to shallow and solvent-exposed binding sites. One way to deal with this problem is to design multivalent structures to achieve huge affinity improvements. Even in the case of a protein with a single binding site like Siglec-8, multivalency can enhance affinity through statistical rebinding, which relies on the increased local concentration of binding moiety. Thus, once the bound ligand dissociates, another one is in close proximity and immediately replaces it. To study this statistical rebinding effect in Siglec-8, different oligovalent ligands were synthesised and tested (Manuscript 1). Thermodynamic analysis showed that each binding epitope contributed enthalpically to the same extent as in the monovalent interaction, while entropic penalties were observed. Dissection of the entropic term in its components for some compounds revealed that greatly favourable solvation entropies were counterbalanced by bigger conformation entropy penalties. Additionally, to take the multivalent presentation concept to its extreme, a glycopolymer was synthesized and tested in cell-based bioassays to demonstrate the binding to Siglec-8. On the other hand, the biological outcome obtained with the best monovalent sulphonamide glycomimetic was much smaller. However, this assay proved the potential of the developed glycomimetic structures, and provided additional proof of the potential pharmacological applications that compounds with improved affinity could have. To further improve the affinity of our glycomimetic Siglec-8 ligands, different strategies were explored (Manuscript 2). Firstly, bioisosteres of the carboxylic acid and sulfate group led to a complete loss of activity towards Siglec-8, confirming the crucial role for these two functionalities. Secondly, the previously unexplored C-4 position of the sialic acid was modified leading to amide derivatives with improved affinity. Finally, second generation sulphonamides were synthesized. While changing the electronic properties of the naphthalene moiety did not influence affinity, the extended aromatic system proved to be more important for having high-affinity compounds

Holographic Tunneling Wave Function

The Hartle-Hawking wave function in cosmology can be viewed as a decaying wave function with anti-de Sitter (AdS) boundary conditions. We show that the growing wave function in AdS familiar from Euclidean AdS/CFT is equivalent, semiclassically and up to surface terms, to the tunneling wave function in cosmology. The cosmological measure in the tunneling state is given by the partition function of certain relevant deformations of CFTs on a locally AdS boundary. We compute the partition function of finite constant mass deformations of the O(N) vector model on the round three sphere and show this qualitatively reproduces the behaviour of the tunneling wave function in Einstein gravity coupled to a positive cosmological constant and a massive scalar. We find the amplitudes of inhomogeneities are not damped in the holographic tunneling state.Comment: 22 pages, 5 figures, Revisions according to the JHEP edito