Poly(amidoamine)s synthesis, characterisation and interaction with BSA

Cationic poly(amidoamine)s (PAAs) were synthesised and characterised by NMR and gel permeation chromatography. Their thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Although poly(amidoamine)s have been used as endosomolytic polymers for protein intracellular delivery, the interaction of the polymers with the proteins still need to be investigated. BSA was used as a model protein and complexation with the different poly(amidoamine) s was investigated using gel retardation assays, fluorescence spectroscopy and high sensitivity differential scanning calorimetry. Our results indicate that the thermal stability of BSA was affected upon interaction and complexation with the poly(amidoamine)s, however these interactions did not seem to modify the structure of the protein. Polymer flexibility seemed to favour polymer/protein complexation and promoted thermal stability

Poly(amidoamine)-BSA conjugates synthesised by Michael addition reaction retained enzymatic activity

Polymer-protein conjugates are key to overcome some of the therapeutic protein limitations, including inefficient intracellular delivery. Poly(amidoamine)s are bioresponsive polyelectrolytes, which can form complexes with proteins and promote their delivery into the cytosol of cells. To investigate if conjugation would affect the activity of the protein, two poly(amidoamine)-BSA conjugates were synthesised using a “grafted to” method and Michael addition reaction. Following purification, the conjugates were characterised by electrophoresis, size exclusion chromatography (Mn(C1) = 140.7 kDa ; Mn(C2) = 218.6 kDa) and light scattering (Dh(C1) = 37.5 nm ; Dh(C2) = 75.1 nm). As a result of the conjugation with the cationic polymer, the conjugates had a positive zeta potential (?(C1) = +15.4 mV; ?(C2) = +20.2 mV). TNBS assays demonstrated that 16% to 25% of the protein amine groups were modified and HPLC analysis indicated that the amount of protein in the conjugate was 0.76 mg of BSA/mg of PAA (C1) and 0.43 mg of BSA /mg of PAA (C2). Enzymatic assays indicated the conjugates displayed an esterase activity similar (C1) or reduced ~ 35% (C2) compare to BSA. Altogether the results demonstrated that the conjugation of poly(amidoamine)s to a model protein can lead to the formation of bioconjugates that retain the enzymatic activity of the native protein. Such conjugates could have some application in protein delivery and enzyme engineering for biocatalysis and biosensors

Diffractive SUSY particle production at the LHC

We give detailed predictions for diffractive SUSY Higgs boson and top squark associated productions at the LHC via the exclusive double pomeron exchange mechanism. We study how the SUSY Higgs cross section and the signal over background ratio are enhanced as a function of tangent beta in different regimes. The prospects are particularly promising in the ``anti-decoupling'' regime, which we study in detail. We also give the prospects for a precise measurement of the top squark mass using the threshold scan of central diffractive associated top squark events at the LHC.Comment: 14 pages, 6 fig

Update on Fermion Mass Models with an Anomalous Horizontal U(1) Symmetry

We reconsider models of fermion masses and mixings based on a gauge anomalous horizontal U(1) symmetry. In the simplest model with a single flavon field and horizontal charges of the same sign for all Standard Model fields, only very few charge assignements are allowed when all experimental data, including neutrino oscillation data, is taken into account. We show that a precise description of the observed fermion masses and mixing angles can easily be obtained by generating sets of the order one parameters left unconstrained by the U(1) symmetry. The corresponding Yukawa matrices show several interesting features which may be important for flavour changing neutral currents and CP violation effects in supersymmetric models.Comment: 23 pages, 8 figure

Higgs as a pseudo-Goldstone boson, the mu problem and gauge-mediated supersymmetry breaking

We study the interplay between the spontaneous breaking of a global symmetry of the Higgs sector and gauge-mediated supersymmetry breaking, in the framework of a supersymmetric model with global SU(3) symmetry. In addition to solving the supersymmetric flavour problem and alleviating the little hierarchy problem, this scenario automatically triggers the breaking of the global symmetry and provides an elegant solution to the mu/Bmu problem of gauge mediation. We study in detail the processes of global symmetry and electroweak symmetry breaking, including the contributions of the top/stop and gauge-Higgs sectors to the one-loop effective potential of the pseudo-Goldstone Higgs boson. While the joint effect of supersymmetry and of the global symmetry allows in principle the electroweak symmetry to be broken with little fine-tuning, the simplest version of the model fails to bring the Higgs mass above the LEP bound due to a suppressed tree-level quartic coupling. To cure this problem, we consider the possibility of additional SU(3)-breaking contributions to the Higgs potential, which results in a moderate fine-tuning. The model predicts a rather low messenger scale, a small tan beta value, a light Higgs boson with Standard Model-like properties, and heavy higgsinos.Comment: 19 pages, 6 figures. New section 3.3 on the mu/Bmu problem, more detailed analytic computation in section 4.1, error in Fig. 5 corrected, significant redactional changes (including abstract, introduction and conclusion) in order to better emphasize the main results of the paper. Title changed in journal. Final version to appear in Eur. Phys. J.

A New Parametrization of the Seesaw Mechanism and Applications in Supersymmetric Models

We present a new parametrization of the minimal seesaw model, expressing the heavy-singlet neutrino Dirac Yukawa couplings $(Y_\nu)_{ij}$ and Majorana masses $M_{N_i}$ in terms of effective light-neutrino observables and an auxiliary Hermitian matrix $H.$ In the minimal supersymmetric version of the seesaw model, the latter can be related directly to other low-energy observables, including processes that violate charged lepton flavour and CP. This parametrization enables one to respect the stringent constraints on muon-number violation while studying the possible ranges for other observables by scanning over the allowed parameter space of the model. Conversely, if any of the lepton-flavour-violating process is observed, this measurement can be used directly to constrain $(Y_\nu)_{ij}$ and $M_{N_i}.$ As applications, we study flavour-violating $\tau$ decays and the electric dipole moments of leptons in the minimal supersymmetric seesaw model.Comment: Important references adde

Constraints on Natural MNS Parameters from |U_e3|

The MNS matrix structure emerging as a result of recent neutrino measurements strongly suggests two large mixing angles (solar and atmospheric) and one small angle (|U_e3| << 1). Especially when combined with the neutrino mass hierarchy, these values turn out to impose rather stringent constraints on possible flavor models connecting the three active fermion generations. Specifically, we show that an extremely small value of |U_e3| would require fine tuning of Majorana mass matrix parameters, particularly in the context of seesaw models.Comment: 21 pages, ReVTeX, 2 .eps figure files, updated references and acknowledgment

Searches for Lepton Flavour Violation at a Linear Collider

We investigate the prospects for detection of lepton flavour violation in sparticle production and decays at a Linear Collider (LC), in models guided by neutrino oscillation data. We consider both slepton pair production and sleptons arising from the cascade decays of non-leptonic sparticles. We study the expected signals when lepton-flavour-violating (LFV) interactions are induced by renormalization effects in the Constrained Minimal Supersymmetric extension of the Standard Model (CMSSM), focusing on the subset of the supersymmetric parameter space that also leads to cosmologically interesting values of the relic neutralino LSP density. Emphasis is given to the complementarity between the LC, which is sensitive to mixing in both the left and right slepton sectors, and the LHC, which is sensitive primarily to mixing in the right sector. We also emphasize the complementarity between searches for rare LFV processes at the LC and in low-energy experiments.Comment: 19 pages, 10 figure

Neutrino mixing and large CP violation in B physics

We show that in see-saw models of neutrino mass a la SUSY SO(10), the observed large mixing in atmospheric neutrinos naturally leads to large b-s transitions. If the associated new CP phase turns out to be large, this SUSY contributions can drastically affect the CP violation in some of the B decay channels yielding the beta and gamma angles of the unitarity triangle. They can even produce sizeable CP asymmetries in some decay modes which are not CP violating in the standard model context. Hence the observed large neutrino mixing makes observations of low energy SUSY effect in some CP violating decay channels potentially promising in spite of the agreement between the Standard Model and data in K and B physics so far.Comment: References adde