Nuclear ab initio calculations of He-6 beta-decay for beyond the Standard Model studies

Precision measurements of beta-decay observables offer the possibility to search for deviations from the Standard Model. A possible discovery of such deviations requires accompanying first-principles calculations. Here we compute the nuclear structure corrections for the beta-decay of He-6 which is of central interest in several experimental efforts. We employ the impulse approximation together with wave functions calculated using the ab initio no-core shell model with potentials based on chiral effective field theory. We use these state-of-the-art calculations to give a novel and comprehensive analysis of theoretical uncertainties. We find that nuclear corrections, which we compute within the sensitivity of future experiments, create significant deviation from the naive Gamow-Teller predictions, making their accurate assessment essential in searches for physics beyond the Standard Model. (C) 2022 The Author(s). Published by Elsevier B.V

Robust semi-automated path extraction for visualising stenosis of the coronary arteries

Computed tomography angiography (CTA) is useful for diagnosing and planning treatment of heart disease. However, contrast agent in surrounding structures (such as the aorta and left ventricle) makes 3-D visualisation of the coronary arteries difficult. This paper presents a composite method employing segmentation and volume rendering to overcome this issue. A key contribution is a novel Fast Marching minimal path cost function for vessel centreline extraction. The resultant centreline is used to compute a measure of vessel lumen, which indicates the degree of stenosis (narrowing of a vessel). Two volume visualisation techniques are presented which utilise the segmented arteries and lumen measure. The system is evaluated and demonstrated using synthetic and clinically obtained datasets

Novel Mannitol-Based Small Molecules for Inhibiting Aggregation of α-Synuclein Amyloids in Parkinson's Disease

The aggregation of the amyloidogenic protein α-synuclein (α-Syn) into toxic oligomers and mature fibrils is the major pathological hallmark of Parkinson's disease (PD). Small molecules that inhibit α-Syn aggregation thus may be useful therapeutics for PD. Mannitol and naphthoquinone-tryptophan (NQTrp) have been shown in the past to inhibit α-Syn aggregation by different mechanisms. Herein, we tested whether the conjugation of Mannitol and NQTrp may result in enhance efficacy toward α-Syn. The molecules were conjugated either by a click linker or via a PEG linker. The effect of the conjugate molecules on α-Syn aggregation in vitro was monitored using Thioflavin T fluorescence assay, circular dichroism, transmission electron microscopy, and Congo red birefringence assay. One of the conjugate molecules was found to be more effective than the two parent molecules and as effective as a mixture of the two. The conjugate molecules attenuated the disruptive effect of α-Syn on artificial membrane of Large Unilamellar Vesicles as monitored by dye leakage assay. The conjugates were found to be have low cytotoxicity and reduced toxicity of α-Syn toward SH-SY5Y neuroblastoma cells. These novel designed entities can be attractive scaffold for the development of therapeutic agents for PD

Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease