Change of direction in the biomechanics of atherosclerosis

The non-uniform distribution of atherosclerosis within the arterial system has been attributed to pro-atherogenic influences of low, oscillatory haemodynamic wall shear stress (WSS) on endothelial cells (EC). This theory is challenged by the changes in lesion location that occur with age in human and rabbit aortas. Furthermore, a number of point-wise comparisons of lesion prevalence and WSS have failed to support it. Here we investigate the hypothesis that multidirectional flow-characterized as the average magnitude of WSS components acting transversely to the mean vector (transWSS)-plays a key role. Maps of lesion prevalence around aortic branch ostia in immature and mature rabbits were compared with equivalent maps of time average WSS, the OSI (an index characterizing oscillatory flow) and transWSS, obtained from computational simulations; Spearman's rank correlation coefficients were calculated for aggregated data and 95% confidence intervals were obtained by bootstrapping methods. Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages. Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS. No correlation supported the low, oscillatory WSS theory. The data are consistent with the view that multidirectional near-wall flow is highly pro-atherogenic. Effects of multidirectional flow on EC, and methods for investigating them, are reviewed. The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI

Estimating arterial cyclic strain from the spacing of endothelial nuclei

Background: The non-uniform distribution of atherosclerosis within the arterial system is widely attributed to variation in haemodynamic wall shear stress. It may also depend on variation in pressure-induced stresses and strains within the arterial wall; these have been less widely investigated, at least in part because of a lack of suitable techniques. Objectives: Here we show that local arterial strain can be determined from impressions left by endothelial cells on the surface of vascular corrosion casts made at different pressures, even though only one pressure can be examined in each vessel. The pattern of pits in the cast caused by protruding endothelial nuclei was subject to “retro-deformation” to identify the pattern that would have occurred in the absence of applied stresses. Methods: Retaining the nearest-neighbour pairs found under this condition, changes in nearest-neighbour vectors were calculated for the pattern seen in the cast, and the ratio of mean changes at different pressures determined. This approach removes errors in simple nearest-neighbour analyses caused by the nearest neighbour changing as deformation occurs. Results: The accuracy, precision and robustness of the approach were validated using simulations. The method was implemented using confocal microscopy of casts of the rabbit aorta made at systolic and diastolic pressures; results agreed well with the ratio of the macroscopic dimensions of the casts. Conclusions: Applying the new technique to areas around arterial branches could support or refute the hypothesis that the development of atherosclerosis is influenced by mural strain, and the method may be applicable to other tissues

The Stress-Energy Tensor of Flavor Fields from AdS/CFT

We use the AdS/CFT correspondence to study the transport properties of massive N=2 hypermultiplet fields in an N=4 SU(Nc) super-Yang-Mills theory plasma in the large Nc, large 't Hooft coupling limit, and in the presence of a baryon number chemical potential and external electric and magnetic fields. In particular, we compute the flavor fields' contribution to the stress-energy tensor. We find infrared divergences in the stress-energy tensor, arising from the flavor fields' constant rate of energy and momentum loss. We regulate these divergences and extract the energy and momentum loss rates from the divergent terms. We also check our result in various limits in which the divergences are absent. The supergravity dual is a system of D7-branes, with a particular configuration of worldvolume fields, probing an AdS-Schwarzschild background. The supergravity calculation amounts to computing the stress-energy tensor of the D7-branes.Comment: 32 pages; v2, added one footnote in section 2.2, added one reference, version published in JHE

Lattice gauge theory for physics beyond the Standard Model

This document is one of a series of whitepapers from the USQCD collaboration. Here, we discuss opportunities for lattice field theory research to make an impact on models of new physics beyond the Standard Model, including composite Higgs, composite dark matter, and supersymmetric theories.Comment: 24 page

Lattice Gauge Theory for Physics Beyond the Standard Model

This document is one of a series of whitepapers from the USQCD collaboration. Here, we discuss opportunities for lattice field theory research to make an impact on models of new physics beyond the Standard Model, including composite Higgs, composite dark matter, and supersymmetric theories

Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model

Atherosclerosis may be triggered by an elevated net transport of lipid-carrying macromolecules from plasma into the arterial wall. We hypothesised that whether lesions are of the thin-cap fibroatheroma (TCFA) type or are less fatty and more fibrous depends on the degree of elevation of transport, with greater uptake leading to the former. We further hypothesised that the degree of elevation can depend on haemodynamic wall shear stress characteristics and nitric oxide synthesis. Placing a tapered cuff around the carotid artery of apolipoprotein E -/- mice modifies patterns of shear stress and eNOS expression, and triggers lesion development at the upstream and downstream cuff margins; upstream but not downstream lesions resemble the TCFA. We measured wall uptake of a macromolecular tracer in the carotid artery of C57bl/6 mice after cuff placement. Uptake was elevated in the regions that develop lesions in hyperlipidaemic mice and was significantly more elevated where plaques of the TCFA type develop. Computational simulations and effects of reversing the cuff orientation indicated a role for solid as well as fluid mechanical stresses. Inhibiting NO synthesis abolished the difference in uptake between the upstream and downstream sites. The data support the hypothesis that excessively elevated wall uptake of plasma macromolecules initiates the development of the TCFA, suggest that such uptake can result from solid and fluid mechanical stresses, and are consistent with a role for NO synthesis. Modification of wall transport properties might form the basis of novel methods for reducing plaque rupture

Nonperturbative investigations of SU(3) gauge theory with eight dynamical flavors

We present our lattice studies of SU(3) gauge theory with $N_f$ = 8 degenerate fermions in the fundamental representation. Using nHYP-smeared staggered fermions we study finite-temperature transitions on lattice volumes as large as $L^3 \times N_t = 48^3 \times 24$, and the zero-temperature composite spectrum on lattice volumes up to $64^3 \times 128$. The spectrum indirectly indicates spontaneous chiral symmetry breaking, but finite-temperature transitions with fixed $N_t \leq 24$ enter a strongly coupled lattice phase as the fermion mass decreases, which prevents a direct confirmation of spontaneous chiral symmetry breaking in the chiral limit. In addition to the connected spectrum we focus on the lightest flavor-singlet scalar particle. We find it to be degenerate with the pseudo-Goldstone states down to the lightest masses reached so far by non-perturbative lattice calculations. Using the same lattice approach, we study the behavior of the composite spectrum when the number of light fermions is changed from eight to four. A heavy flavor-singlet scalar in the 4-flavor theory affirms the contrast between QCD-like dynamics and the low-energy behavior of the 8-flavor theory.Comment: 31 pages, 36 figures, 8 tables. v2: update to published versio

The Global Diversity of Parasitic Isopods Associated with Crustacean Hosts (Isopoda: Bopyroidea and Cryptoniscoidea)

Parasitic isopods of Bopyroidea and Cryptoniscoidea (commonly referred to as epicarideans) are unique in using crustaceans as both intermediate and definitive hosts. In total, 795 epicarideans are known, representing ∼7.7% of described isopods. The rate of description of parasitic species has not matched that of free-living isopods and this disparity will likely continue due to the more cryptic nature of these parasites. Distribution patterns of epicarideans are influenced by a combination of their definitive (both benthic and pelagic species) and intermediate (pelagic copepod) host distributions, although host specificity is poorly known for most species. Among epicarideans, nearly all species in Bopyroidea are ectoparasitic on decapod hosts. Bopyrids are the most diverse taxon (605 species), with their highest diversity in the North West Pacific (139 species), East Asian Sea (120 species), and Central Indian Ocean (44 species). The diversity patterns of Cryptoniscoidea (99 species, endoparasites of a diverse assemblage of crustacean hosts) are distinct from bopyrids, with the greatest diversity of cryptoniscoids in the North East Atlantic (18 species) followed by the Antarctic, Mediterranean, and Arctic regions (13, 12, and 8 species, respectively). Dajidae (54 species, ectoparasites of shrimp, mysids, and euphausids) exhibits highest diversity in the Antarctic (7 species) with 14 species in the Arctic and North East Atlantic regions combined. Entoniscidae (37 species, endoparasites within anomuran, brachyuran and shrimp hosts) show highest diversity in the North West Pacific (10 species) and North East Atlantic (8 species). Most epicarideans are known from relatively shallow waters, although some bopyrids are known from depths below 4000 m. Lack of parasitic groups in certain geographic areas is likely a sampling artifact and we predict that the Central Indian Ocean and East Asian Sea (in particular, the Indo-Malay-Philippines Archipelago) hold a wealth of undescribed species, reflecting our knowledge of host diversity patterns

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License