Geometric Path Integrals. A Language for Multiscale Biology and Systems Robustness

In this paper we suggest that, under suitable conditions, supervised learning can provide the basis to formulate at the microscopic level quantitative questions on the phenotype structure of multicellular organisms. The problem of explaining the robustness of the phenotype structure is rephrased as a real geometrical problem on a fixed domain. We further suggest a generalization of path integrals that reduces the problem of deciding whether a given molecular network can generate specific phenotypes to a numerical property of a robustness function with complex output, for which we give heuristic justification. Finally, we use our formalism to interpret a pointedly quantitative developmental biology problem on the allowed number of pairs of legs in centipedes

Solvable model of dissipative dynamics in the deep strong coupling regime

We describe the dynamics of a qubit interacting with a bosonic mode coupled to a zero-temperature bath in the deep strong coupling (DSC) regime. We provide an analytical solution for this open system dynamics in the off-resonance case of the qubit-mode interaction. Collapses and revivals of parity chain populations and the oscillatory behavior of the mean photon number are predicted. At the same time, photon number wave packets, propagating back and forth along parity chains, become incoherently mixed. Finally, we investigate numerically the effect of detuning on the validity of the analytical solution.Comment: 6 pages, 8 figure

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa.

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa

Updated Nucleosynthesis Constraints on Unstable Relic Particles

We revisit the upper limits on the abundance of unstable massive relic particles provided by the success of Big-Bang Nucleosynthesis calculations. We use the cosmic microwave background data to constrain the baryon-to-photon ratio, and incorporate an extensively updated compilation of cross sections into a new calculation of the network of reactions induced by electromagnetic showers that create and destroy the light elements deuterium, he3, he4, li6 and li7. We derive analytic approximations that complement and check the full numerical calculations. Considerations of the abundances of he4 and li6 exclude exceptional regions of parameter space that would otherwise have been permitted by deuterium alone. We illustrate our results by applying them to massive gravitinos. If they weigh ~100 GeV, their primordial abundance should have been below about 10^{-13} of the total entropy. This would imply an upper limit on the reheating temperature of a few times 10^7 GeV, which could be a potential difficulty for some models of inflation. We discuss possible ways of evading this problem.Comment: 40 pages LaTeX, 18 eps figure

Football, religion and ethnicity Irish identity in Scotland

SIGLEAvailable from British Library Document Supply Centre-DSC:4574.825(9) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Hippocampal atrophy and intrinsic brain network alterations relate to impaired capacity for mind wandering in neurodegeneration

Mind wandering represents the human capacity for internally focussed thought, and relies upon dynamic interactions between default and frontoparietal networks. The majority of studies in the field have characterised mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. The present study used a validated thought sampling task, to probe the capacity for mind wandering in two neurodegenerative disorders; the behavioural variant of frontotemporal dementia (n=28) and Alzheimer’s disease (n=22), compared to healthy older controls (n=28). These disorders were selected due to their canonical profiles of neural dysfunction across key sites of the default and frontoparietal networks. Behaviourally, mind wandering frequency was found to be reduced in the patient groups, leading to an increase in stimulus-bound thoughts. These behavioural profiles were associated with distinct regions of grey matter loss, as revealed by voxel-based morphometry, predominantly in the hippocampal complex and striatum. Resting state functional connectivity further revealed associations between impaired mind wandering performance and altered connectivity within and between regions of the frontoparietal and default networks. Together, these findings are the first to describe altered mind wandering in neurodegenerative disorders, which was associated with hippocampal atrophy and aberrations in the functional integrity of the default and frontoparietal networks. These results corroborate current theoretical frameworks emphasising that cooperation between default and frontoparietal regions is critical for producing and sustaining internally focussed thought. Notably this study reveals a new dimension of cognitive dysfunction not previously documented in neurodegenerative disorders

Lung-Targeted Delivery of Dimethyl Fumarate Promotes the Reversal of Age-Dependent Established Lung Fibrosis

Idiopathic pulmonary fibrosis (IPF), a severe and deadly form of lung fibrosis, is widely regarded as a disease of aging. We previously demonstrated that aged mice with persistent lung fibrosis and IPF lung myofibroblasts exhibit deficient Nrf2-mediated antioxidant responses. Tecfidera is an orally administered FDA-approved drug for the treatment of multiple sclerosis, where the active pharmaceutical ingredient is dimethyl fumarate (DMF), an active Nrf2 activator. However, no studies have evaluated the efficacy of DMF for age-associated persistent lung fibrosis. Here, we demonstrate that in IPF lung fibroblasts, DMF treatment inhibited both TGF-β-mediated pro-fibrotic phenotypes and led to a reversal of established pro-fibrotic phenotypes. We also evaluated the pre-clinical efficacy of lung-targeted (inhaled) vs. systemic (oral) delivery of DMF in an aging murine model of bleomycin-induced persistent lung fibrosis. DMF or vehicle was administered daily to aged mice by oral gavage or intranasal delivery from 3-6 weeks post-injury when mice exhibited non-resolving lung fibrosis. In contrast to systemic (oral) delivery, only lung-targeted (inhaled) delivery of DMF restored lung Nrf2 expression levels, reduced lung oxidative stress, and promoted the resolution of age-dependent established fibrosis. This is the first study to demonstrate the efficacy of lung-targeted DMF delivery to promote the resolution of age-dependent established lung fibrosis. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]