Heart Regeneration: Opportunities and Challenges for Drug Discovery with Novel Chemical and Therapeutic Methods or Agents

Following a heart attack, more than a billion cardiac muscle cells (cardiomyocytes) can be killed, leading to heart failure and sudden death. Much research in this area is now focused on the regeneration of heart tissue through differentiation of stem cells, proliferation of existing cardiomyocytes and cardiac progenitor cells, and reprogramming of fibroblasts into cardiomyocytes. Different chemical modalities (i.e. methods or agents), ranging from small molecules and RNA approaches (including both microRNA and anti‐microRNA) to modified peptides and proteins, are showing potential to meet this medical need. In this Review, we outline the recent advances in these areas and describe both the modality and progress, including novel screening strategies to identify hits, and the upcoming challenges and opportunities to develop these hits into pharmaceuticals, at which chemistry plays a key role.     

Adsorption of four non-ionic cellulose derivatives on cellulose model surfaces

The adsorption of four commercial non-ionic cellulose derivatives onto two different model surfaces of cellulose fibres has been studied with surface plasmon reflectance. The model surfaces of cellulose were ultrathin films of either nano fibrillated cellulose or regenerated cellulose on Au(s). Partial least squares models were used in the analysis of the data and it was found that the type of cellulose model surface seems to be most important for both the total adsorption and the initial adsorption rate of the studied cellulose derivatives. It is believed that this can be explained by morphological differences between the surfaces, and it was found that the properties of the cellulose derivatives that affect the adsorption of the two types of cellulose surface differ. For adsorption onto a NFC-based model surface, the type of cellulose derivative and the polydispersity index (PDI) of the cellulose derivative seem to be the two most important variables for the observed adsorption of these cellulose derivatives. For the regenerated cellulose surface the three most important variables are the M _n of the cellulose derivatives, the DS _NMR of the methyl celluloses, and PDI of the cellulose derivatives. Thus the adsorption of cellulose derivatives on the NFC-based cellulose model surface is strongly affected by the type of substituent, while the same cannot be said for a surface regenerated from N-methylmorpholine-N-oxide. Additionally, the DS _NMR of methyl celluloses affects their adsorption differently on the investigated cellulose model surfaces.     

Unbounded derivations tangential to compact groups of automorphisms

We consider unbounded derivations in C¹-algebras commuting with compact groups of ¹-automorphisms. A closed ¹-derivation δ in a C¹-algebra $\text{U}$ is said to be a generator if there exists a strongly continuous one-parameter subgroup t∈$\text{R}$→τ(t)? Aut($\text{U}$) such that $\text{δ =}\text{d}\text{dt}\text{τ(t)¦}{}_{\mathrm{t\; =\; 0}}$. If δ is known to commute with a compact abelian action α:G→Aut($\text{U}$), and if δ(a) = 0 for all a in the fixed point algebra $\text{U}$^α of the action G, then we show that δ is necessarily a generator. Moreover, in any faithful G-covariant representation, there is a commutative operator field γ ∈ ? → v(γ) such that $\text{v(γ)}{}^1\text{= ?v(γ), v(γ)}$ is possibly unbounded but affiliated with the center of {$\text{U}$^α}″, and e^tδ(x) = xe^tv(γ) for all x in the Arveson spectral subspace $\text{U}$^α(γ). In particular, if $\text{U}$ is the CAR algebra over an infinite-dimensional Hilbert space and α is the gauge group, then any such derivation δ is a scalar multiple of the generator of the gauge group.     

On the application of a single‐crystal κ‐diffractometer and a CCD area detector for studies of thin films

A multipurpose six‐axis κ‐diffractometer, together with the brilliance of the ESRF light source and a CCD area detector, has been explored for studying epitaxial relations and crystallinity in thin film systems. The geometrical flexibility of the six‐axis goniometer allows measurement of a large volume in reciprocal space, providing an in‐depth understanding of sample crystal relationships. By a set of examples of LaAlO₃ thin films deposited by the atomic layer deposition technique, the possibilities of the set‐up are presented. A fast panoramic scan provides determination of the crystal orientation matrices, prior to more thorough inspection of single Bragg nodes. Such information, in addition to a broadening analysis of families of single reflections, is shown to correlate well with the crystallinity, crystallite size, strain and epitaxial relationships in the thin films. The proposed set‐up offers fast and easy sample mounting and alignment, along with crucial information on key features of the thin film structures.     

A sublogarithmic convex hull algorithm

We present a parallel algorithm for finding the convex hull of a sorted set of points in the plane. Our algorithm runs inO(logn/log logn) time usingO(n log logn/logn) processors in theCommon crcw pram computational model, which is shown to be time and cost optimal. The algorithm is based onn ^1/3 divide-and-conquer and uses a simple pointer-based data structure.Part of this work was done when the last three authors were at the Department of Computer and Information Science, Linköping University. The research of the second author was supported by the Academy of Finland.     

Deposition of thin films of organic-inorganic hybrid materials based on aromatic carboxylic acids by atomic layer deposition

Thin films of organic-inorganic hybrid materials have been grown by the atomic layer deposition (ALD) technique, using trimethylaluminium (TMA) and aromatic carboxylic acids such as 1,2-benzene dicarboxylic acid, 1,3-benzene dicarboxylic acid, 1,4-benzene dicarboxylic acid, 1,3,5-benzene tricarboxylic acid, 1,2,4,5-benzene tetracarboxylic acid as precursors. Growth rates as function of temperature show that all systems, with the exception of the benzoic acid-TMA system, possess ALD-windows and provides growth rates in the range of 0.25-1.34 nm/cycle. X-ray diffraction studies of the as-deposited films reveal their amorphous character, which is also supported by very low surface roughness as measured by atomic force microscopy. As-deposited films were investigated by Fourier Transform Infrared Spectroscopy proving that the deposited films are of a hybrid character.     

Synthesis and Self‐Aggregation of Enantiopure and Racemic Molecular Tweezers Based on the Bicyclo[3.3.1]nonane Framework

A pair of molecular tweezers (syn‐ 4 ) that consists of quinoline and pyrazine units fused to a bicyclic framework is presented. The tweezers were synthesised both as a racemic mixture (rac‐ 4 ) and an enantiomerically pure form ((R,R,R,R)‐ 4 ) starting from either racemic or enantiomerically pure bicyclo[3.3.1]nonane‐2,6‐dione ( 3 ). Homochiral dimers were observed in the solid state for rac‐ 4 . The self‐association of both rac‐ 4 and (R,R,R,R)‐ 4 was studied in solution. A weak self‐association constant in CDCl₃ was estimated by ¹H NMR spectroscopic dilution titration experiments in both cases, following several proton resonances. For this purpose, a general normalisation model for the accurate determination of association constants from multiple datasets was developed. In contrast to the solid state, no diastereomeric discrimination was observed for rac‐ 4 in solution.