Infinitely divisible metrics and curvature inequalities for operators in the Cowen-Douglas class

The curvature (T)(w) of a contraction T in the Cowen-Douglas class B-1() is bounded above by the curvature (S*)(w) of the backward shift operator. However, in general, an operator satisfying the curvature inequality need not be contractive. In this paper, we characterize a slightly smaller class of contractions using a stronger form of the curvature inequality. Along the way, we find conditions on the metric of the holomorphic Hermitian vector bundle E-T corresponding to the operator T in the Cowen-Douglas class B-1() which ensures negative definiteness of the curvature function. We obtain a generalization for commuting tuples of operators in the class B-1() for a bounded domain in C-m.

Metal nanoparticles as better protein-aggregation prevention agents than chaperones

Prevention or suppression of protein aggregation is of great importance in the context of protein storage, transportation and delivery. Traditionally chaperones or other chemically active agents are used to stop or diffuse native protein aggregation. We have used gold nanoparticles to prevent thermal aggregation of alcohol dehydrogenase (ADH), a protein that maintains the alcohol level in the liver and stomach. A light-scattering assay has been used to investigate the effect of gold nanoparticles on thermal aggregation of ADH and the result of our study has been summarized in Fig. 1. The scattered light intensity from the solution containing ADH decreases when 45 nm gold nanoparticles are added prior to heating (thermal denaturation) the solution, which indicates prevention of aggregation. The aggregation of the protein is suppressed to the extent of 96% with picomolar concentration of 45 nm gold nanoparticles while micromolar amounts of other proteins and biological substances are necessary to achieve the same effect. The extent varies with the size and the concentration of the gold NPs for the same protein concentration.

In vitro Evidence that an Aqueous Extract of Centella asiatica Modulates alpha-Synuclein Aggregation Dynamics

alpha-Synuclein aggregation is one of the major etiological factors implicated in Parkinson's disease (PD). The prevention of aggregation of alpha-synuclein is a potential therapeutic intervention for preventing PD. The discovery of natural products as alternative drugs to treat PD and related disorders is a current trend. The aqueous extract of Centella asiatica (CA) is traditionally used as a brain tonic and CA is known to improve cognition and memory. There are limited data on the role of CA in modulating amyloid-beta (A beta) levels in the brain and in A beta aggregation. Our study focuses on CA as a modulator of the alpha-synuclein aggregation pattern in vitro. Our investigation is focused on: (i) whether the CA leaf aqueous extract prevents the formation of aggregates from monomers (Phase I: alpha-synuclein + extract co-incubation); (ii) whether the CA aqueous extract prevents the formation of fibrils from oligomers (Phase II: extract added after oligomers formation); and (iii) whether the CA aqueous extract disintegrates the pre-formed fibrils (Phase III: extract added to mature fibrils and incubated for 9 days). The aggregation kinetics are studied using a thioflavin-T assay, circular dichroism, and transmission electron microscopy. The results showed that the CA aqueous extract completely inhibited the alpha-synuclein aggregation from monomers. Further, CA extract significantly inhibited the formation of oligomer to aggregates and favored the disintegration of the preformed fibrils. The study provides an insight in finding new natural products for future PD therapeutics.

Tripodal Bile Acid Architectures Based on a Triarylphosphine Oxide Core Obtained by Copper-Catalysed 1,3]-Dipolar Cycloaddition: Synthesis and Preliminary Aggregation Studies

We report the synthesis and aggregation behaviour of new water-soluble, bile acid derived tripodal architectures based on a core derived from triphenylphosphine oxide. We employed the well-established copper-catalysed 1,3]-dipolar cycloaddition (CuAAC) for the construction of these tripodal molecules. The aggregation behaviour of these molecules in aqueous media was studied by different analytical methods such as dye solubilisation, dynamic light scattering, NMR and AFM. These molecular architectures also offer an additional advantage in aiding understanding of the influence of the nature of the bile acid backbone and of the configuration at the steroid C-3 position in these architectures; to the best of our knowledge this has not been reported in the literature. The unique gelation properties of the -derivatives were explained through molecular modelling studies and the mechanical behaviour of these gels was studied by rheology experiments.

Flag structure for operators in the Cowen-Douglas class

The explicit description of homogeneous operators and localization of a Hilbert module naturally leads to the definition of a class of Cowen-Douglas operators possessing a flag structure. These operators are irreducible. We show that the flag structure is rigid in the sense that the unitary equivalence class of the operator and the flag structure determine each other. We obtain a complete set of unitary invariants which are somewhat more tractable than those of an arbitrary operator in the Cowen-Douglas class. (C) 2014 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Revisiting neutrino masses from Planck scale operators

Planck scale lepton number violation is an interesting and natural possibility to explain nonzero neutrino masses. We consider such operators in the context of Randall-Sundrum (RS1) scenarios. Implementation of this scenario with a single Higgs localized on the IR brane (standard RS1) is not phenomenologically viable as they lead to inconsistencies in the charged lepton mass fits. In this paper we propose a setup with two Higgs doublets. We present a detailed numerical analysis of the fits to fermion masses and mixing angles. This model solves the issues regarding the fermion mass fits but solutions with consistent electroweak symmetry breaking are highly fine-tuned. A simple resolution is to consider supersymmetry in the bulk and a detailed discussion of which is provided. Constraints from flavor are found to be strong and minimal flavor violation (MFV) is imposed to alleviate them.

Fine-Tuning Dual Emission and Aggregation-Induced Emission Switching in NPI-BODIPY Dyads

Three new NPI-BODIPY dyads 1-3 (NPI = 1,8-naphthalimide, BODIPY = boron-dipyrromethene) were synthesized, characterized, and studied. The NPI and BODIPY moieties in these dyads are electronically separated by oxoaryl bridges, and the compounds only differ structurally with respect to methyl substituents on the BODIPY fluorophore. The NPI and BODIPY moieties retain their optical features in molecular dyads 1-3. Dyads 1-3 show dual emission in solution originating from the two separate fluorescent units. The variations of the dual emission in these compounds are controlled by the structural flexibilities of the systems. Dyads 13, depending on their molecular flexibilities, show considerably different spectral shapes and dissimilar intensity ratios of the two emission bands. The dyads also show significant aggregation-induced emission switching (AIES) on formation of nano-aggregates in THF/H2O with changes in emission color from green to red. Whereas the flexible and aggregation-prone compound 1 shows AIES, rigid systems with less favorable intermolecular interactions (i.e., 2 and 3) show aggregation-induced quenching of emission. Correlations of the emission intensity and structural flexibility were found to be reversed in solution and aggregated states. Photophysical and structural investigations suggested that intermolecular interactions (e. g., pi-pi stacking) play a major role in controlling the emission of these compounds in the aggregated state.

Efficient simulation of unitary operators by combining two numerical algorithms: An NMR simulation of the mirror-inversion propagator of an XY spin chain

Precise experimental implementation of unitary operators is one of the most important tasks for quantum information processing. Numerical optimization techniques are widely used to find optimized control fields to realize a desired unitary operator. However, finding high-fidelity control pulses to realize an arbitrary unitary operator in larger spin systems is still a difficult task. In this work, we demonstrate that a combination of the GRAPE algorithm, which is a numerical pulse optimization technique, and a unitary operator decomposition algorithm Ajoy et al., Phys. Rev. A 85, 030303 (2012)] can realize unitary operators with high experimental fidelity. This is illustrated by simulating the mirror-inversion propagator of an XY spin chain in a five-spin dipolar coupled nuclear spin system. Further, this simulation has been used to demonstrate the transfer of entangled states from one end of the spin chain to the other end.

Jacobi forms and differential operators

We affirmatively answer a question due to S. Bocherer concerning the feasibility of removing one differential operator from the standard collection of m + 1 of them used to embed the space of Jacobi forms of weight 2 and index m into several pieces of elliptic modular forms. (C) 2014 Elsevier Inc. All rights reserved.

Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

Huntington's disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK. (C) 2014 Elsevier Inc. All rights reserved.

Admissible fundamental operators(star)

Let F and G be two bounded operators on two Hilbert spaces. Let their numerical radii be no greater than one. This note investigates when there is a Gamma-contraction (S, P) such that F is the fundamental operator of (S, P) and G is the fundamental operator of (S*, P*). Theorem 1 puts a necessary condition on F and G for them to be the fundamental operators of (S, P) and (S*, P*) respectively. Theorem 2 shows that this necessary condition is also sufficient provided we restrict our attention to a certain special case. The general case is investigated in Theorem 3. Some of the results obtained for Gamma-contractions are then applied to tetrablock contractions to figure out when two pairs (F1, F2) and (G(1), G(2)) acting on two Hilbert spaces can be fundamental operators of a tetrablock contraction (A, B, P) and its adjoint (A*, B*, P*) respectively. This is the content of Theorem 3. (C) 2015 Elsevier Inc. All rights reserved.

Suppression of protein aggregation by gold nanoparticles: a new way to store and transport proteins

Suppression of the aggregation of proteins has tremendous implications in biology and medicine. In the pharmaceuticals industry, aggregation of therapeutically important proteins and peptides while stored, reduces the efficacy and promptness of action leading to, in many instances, intoxication of the patient by the aggregate. Here we report the effect of gold nanoparticles (Au-NPs) in preventing the thermal and chemical aggregation of two unrelated proteins of different size, alcohol dehydrogenase (ADH, 84 kDa) and insulin (6 kDa), respectively, in physiological pH. Our principal observation is that there is a significant reduction (up to 95%) in the extent of aggregation of ADH and insulin in the presence of gold nanoparticles (Au-NPs). Aggregation of these proteins at micromolar concentration is prevented using nanomolar or less amounts of gold nanoparticles which is remarkable since chaperones which prevent such aggregation in vivo are required in micromolar quantity. The prevention of aggregation of these two different proteins under two different denaturing environments has established the role of Au-NPs as a protein aggregation prevention agent. The extent of prevention increases rapidly with the increase in the size of the gold nanoparticles. Protein molecules get physisorbed on the gold nanoparticle surface and thus become inaccessible by the denaturing agent in solution. This adsorption of proteins on AuNPs has been established by a variety of techniques and assays.

Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant alpha-Synuclein

Accumulating evidence suggests that deposition of neurotoxic a-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson's disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against a-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of a-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of a-synuclein amyloidosis and toxicity in Parkinson's disease and other synucleinopathies.

Interferon-Gamma and Nitric Oxide Synthase 2 Mediate the Aggregation of Resident Adherent Peritoneal Exudate Cells: Implications for the Host Response to Pathogens

Interferon-gamma (Ifn gamma), a key macrophage activating cytokine, plays pleiotropic roles in host immunity. In this study, the ability of Ifn gamma to induce the aggregation of resident mouse adherent peritoneal exudate cells (APECs), consisting primarily of macrophages, was investigated. Cell-cell interactions involve adhesion molecules and, upon addition of Ifn gamma, CD11b re-localizes preferentially to the sites of interaction on APECs. A functional role of CD11b in enhancing aggregation is demonstrated using Reopro, a blocking reagent, and siRNA to Cd11b. Studies with NG-methyl-L-arginine (LNMA), an inhibitor of Nitric oxide synthase (Nos), NO donors, e.g., S-nitroso-N-acetyl-DL-penicillamine (SNAP) or Diethylenetriamine/ nitric oxide adduct (DETA/NO), and Nos2(-/-) mice identified Nitric oxide (NO) induced by Ifn gamma as a key regulator of aggregation of APECs. Further studies with Nos2(-/-) APECs revealed that some Ifn. responses are independent of NO: induction of MHC class II and CD80. On the other hand, Nos2 derived NO is important for other functions: motility, phagocytosis, morphology and aggregation. Studies with cytoskeleton depolymerizing agents revealed that Ifn gamma and NO mediate the cortical stabilization of Actin and Tubulin which contribute to aggregation of APECs. The biological relevance of aggregation of APECs was delineated using infection experiments with Salmonella Typhimurium (S. Typhimurium). APECs from orally infected, but not uninfected, mice produce high amounts of NO and aggregate upon ex vivo culture in a Nos2-dependent manner. Importantly, aggregated APECs induced by Ifn gamma contain fewer intracellular S. Typhimurium compared to their single counterparts post infection. Further experiments with LNMA or Reopro revealed that both NO and CD11b are important for aggregation; in addition, NO is bactericidal. Overall, this study elucidates novel roles for Ifn gamma and Nos2 in regulating Actin, Tubulin, CD11b, motility and morphology during the aggregation response of APECs. The implications of aggregation or ``group behavior'' of APECs are discussed in the context of host resistance to infectious organisms.