Functional Renormalisation Group Approach for Tensorial Group Field Theory: a Rank-3 Model

We set up the Functional Renormalisation Group formalism for Tensorial Group Field Theory in full generality. We then apply it to a rank-3 model over U(1) x U(1) x U(1), endowed with a linear kinetic term and nonlocal interactions. The system of FRG equations turns out to be non-autonomous in the RG flow parameter. This feature is explained by the existence of a hidden scale, the radius of the group manifold. We investigate in detail the opposite regimes of large cut-off (UV) and small cut-off (IR) of the FRG equations, where the system becomes autonomous, and we find, in both case, Gaussian and non-Gaussian fixed points. We derive and interpret the critical exponents and flow diagrams associated with these fixed points, and discuss how the UV and IR regimes are matched at finite N. Finally, we discuss the evidence for a phase transition from a symmetric phase to a broken or condensed phase, from an RG perspective, finding that this seems to exist only in the approximate regime of very large radius of the group manifold, as to be expected for systems on compact manifolds.Comment: 27 pages, 14 figures; v2: some clarifications added, minor changes, matches published versio

An albumin-derived peptide scaffold capable of binding and catalysis

We have identified a 101-amino-acid polypeptide derived from the sequence surrounding the IIA binding site of human albumin. The polypeptide contains residues that make contact with ligands as warfarin in the parent protein, and eight cysteine residues to form disulfide bridges, which stabilize the polypeptide structure. Seventy-four amino acids are located in six [alpha]-helical regions, with the remaining amino acids forming six connecting coil/loop regions. Codon usage optimization was used to express a GST fusion protein in E. coli in yields as high as 4 mg/l. This fusion protein retains its structural integrity and aldolase activity, the ability to direct the stereochemical outcome of a diketone reduction, and its binding capacity to warfarin and efavirenz. Notably, this newly cloned polypeptide represents a valuable starting point for the construction of libraries of binders and catalysts with improved proficiency

In silico screening of mutational effects on enzyme-proteic inhibitor affinity: a docking-based approach

<p>Abstract</p> <p>Background</p> <p>Molecular recognition between enzymes and proteic inhibitors is crucial for normal functioning of many biological pathways. Mutations in either the enzyme or the inhibitor protein often lead to a modulation of the binding affinity with no major alterations in the 3D structure of the complex.</p> <p>Results</p> <p>In this study, a rigid body docking-based approach has been successfully probed in its ability to predict the effects of single and multiple point mutations on the binding energetics in three enzyme-proteic inhibitor systems. The only requirement of the approach is an accurate structural model of the complex between the wild type forms of the interacting proteins, with the assumption that the architecture of the mutated complexes is almost the same as that of the wild type and no major conformational changes occur upon binding. The method was applied to 23 variants of the ribonuclease inhibitor-angiogenin complex, to 15 variants of the barnase-barstar complex, and to 8 variants of the bovine pancreatic trypsin inhibitor-β Trypsin system, leading to thermodynamic and kinetic estimates consistent with in vitro data. Furthermore, simulations with and without explicit water molecules at the protein-protein interface suggested that they should be included in the simulations only when their positions are well defined both in the wild type and in the mutants and they result to be relevant for the modulation of mutational effects on the association process.</p> <p>Conclusion</p> <p>The correlative models built in this study allow for predictions of mutational effects on the thermodynamics and kinetics of association of three substantially different systems, and represent important extensions of our computational approach to cases in which it is not possible to estimate the absolute free energies. Moreover, this study is the first example in the literature of an extensive evaluation of the correlative weights of the single components of the ZDOCK score on the thermodynamics and kinetics of binding of protein mutants compared to the native state.</p> <p>Finally, the results of this study corroborate and extend a previously developed quantitative model for in silico predictions of absolute protein-protein binding affinities spanning a wide range of values, i.e. from -10 up to -21 kcal/mol.</p> <p>The computational approach is simple and fast and can be used for structure-based design of protein-protein complexes and for in silico screening of mutational effects on protein-protein recognition.</p

Hecke cycles on moduli of vector bundles and orbital degeneracy loci

Given a smooth genus two curve $C$, the moduli space SU$_C(3)$ of rank three semi-stable vector bundles on $C$ with trivial determinant is a double cover in $\mathbb{P}^8$ branched over a sextic hypersurface, whose projective dual is the famous Coble cubic, the unique cubic hypersurface that is singular along the Jacobian of $C$. In this paper we continue our exploration of the connections of such moduli spaces with the representation theory of $GL_9$, initiated in \cite{GSW} and pursued in \cite{GS, sam-rains1, sam-rains2, bmt}. Starting from a general trivector $v$ in $\wedge^3\mathbb{C}^9$, we construct a Fano manifold $D_{Z_{10}}(v)$ in $G(3,9)$ as a so-called orbital degeneracy locus, and we prove that it defines a family of Hecke lines in SU$_C(3)$. We deduce that $D_{Z_{10}}(v)$ is isomorphic to the odd moduli space SU$_C(3, \mathcal{O}_C(c))$ of rank three stable vector bundles on $C$ with fixed effective determinant of degree one. We deduce that the intersection of $D_{Z_{10}}(v)$ with a general translate of $G(3,7)$ in $G(3,9)$ is a K3 surface of genus $19$

Cryopreservation protocol for human biliary tree stem/progenitors, hepatic and pancreatic precursors

Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin. Cryopreserved versus freshly isolated hBTSCs were equally able to engraft into immunocompromised mice yielding cells with human-specific gene expression and human albumin levels in murine serum that were higher for cryopreserved than for freshly isolated hBTSCs. The successful cryopreservation of hBTSCs facilitates establishment of hBTSCs cell banking offering logistical advantages for clinical programs for treatment of liver diseases

Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression

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New cinnamic acid sugar esters as potential UVB filters: Synthesis, cytotoxicity, and physicochemical properties

: Cinnamic Acid Sugar Ester Derivatives (CASEDs) are a class of natural compounds that exhibit several interesting biological activities. However, to date, no examples of their use in sunscreen formulations have been reported. Here, we describe the synthesis of a series of novel cinnamic acid esters of glucose (4a-g), ribose (4h) and lactose (4i) starting from the respective acetals 3. The latter were obtained through oxidative alkoxycarbonylation of olefins. For all compounds 3 and 4, UV-Vis spectra were recorded and lipophilicity (i.e., clogP) and cytotoxicity were evaluated. All but one of the synthesized compounds were found to be non-cytotoxic at the concentrations tested and, as expected, absorption spectra depended only on the substituents on the aromatic ring. Finally, the ad hoc synthesized compound 3k, featuring a 4-methoxy substituent on the phenyl ring and a 1,2-O-isopropylidene ribose moiety, provided the most promising results for a possible use as a sunscreen. Indeed, its Sun Protection Factor (SPF), calculated in vitro, was higher with respect to that of ethylhexyl methoxycinnamate (EHMC), which is already utilized in sun care products. Moreover, 3k showed greater antioxidant properties than EHMC, effectively protecting keratinocytes against H2O2-induced oxidative damage. At the same time, it showed no cytotoxic effects and preserved cellular metabolic activity and protein content. Based on these results, we believe that CASEDs could find valid applications in the skincare and cosmetics sectors

Effect of early stress on hippocampal gray matter is influenced by a functional polymorphism in EAAT2 in bipolar disorder

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