M. T. Joyner & Son- Mrs. R. H. Walker, September 19, 1928

Correspondence: From L.A. Joyner, M.T. Joyner & Son, 515 Main Street, Jacksonville, Florida, to Rosa G. Holmes Walker, Jacksonville, Florida, letter asking for a couple of days grace

Buckling without bending: a new paradigm in morphogenesis

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out-of-phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in-phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2d morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluid-like film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential". Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale-invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bio-inspired applications, and address how our model is and is not unique to the developing nervous system.Comment: version accepted by Physical Review

The unique chemistry of Eastern Mediterranean water masses selects for distinct microbial communities by depth

Peer reviewedPublisher PD

Robust Chauvenet Outlier Rejection

Sigma clipping is commonly used in astronomy for outlier rejection, but the number of standard deviations beyond which one should clip data from a sample ultimately depends on the size of the sample. Chauvenet rejection is one of the oldest, and simplest, ways to account for this, but, like sigma clipping, depends on the sample's mean and standard deviation, neither of which are robust quantities: Both are easily contaminated by the very outliers they are being used to reject. Many, more robust measures of central tendency, and of sample deviation, exist, but each has a tradeoff with precision. Here, we demonstrate that outlier rejection can be both very robust and very precise if decreasingly robust but increasingly precise techniques are applied in sequence. To this end, we present a variation on Chauvenet rejection that we call "robust" Chauvenet rejection (RCR), which uses three decreasingly robust/increasingly precise measures of central tendency, and four decreasingly robust/increasingly precise measures of sample deviation. We show this sequential approach to be very effective for a wide variety of contaminant types, even when a significant -- even dominant -- fraction of the sample is contaminated, and especially when the contaminants are strong. Furthermore, we have developed a bulk-rejection variant, to significantly decrease computing times, and RCR can be applied both to weighted data, and when fitting parameterized models to data. We present aperture photometry in a contaminated, crowded field as an example. RCR may be used by anyone at https://skynet.unc.edu/rcr, and source code is available there as well.Comment: 62 pages, 48 figures, 7 tables, accepted for publication in ApJ

Global Experiential and Didactic Education Opportunities at US Colleges and Schools of Pharmacy

Objective. To assess the characteristics of global experiential and didactic education offerings in the pharmacy curricula

Osteopontin Inhibits Interleukin-1β-Stimulated Increases in Matrix Metalloproteinase Activity in Adult Rat Cardiac Fibroblasts: Role of Protein Kinase C-ζ

We have shown that osteopontin (OPN), an extracellular matrix protein, plays an important role in post myocardial infarction (MI) remodeling by promoting collagen synthesis and accumulation. Interleukin-1β (IL-1β), increased in the heart following MI, increases matrix metalloproteinase (MMP) activity in cardiac fibroblasts in vitro. Here, we show that OPN alone has no effect on MMP activity or expression. However, it reduces IL-1β-stimulated increases in MMP activity and expression in adult rat cardiac fibroblasts. Pretreatment with bovine serum albumin had no effect on MMP activity or protein content, whereas GRGDS (glycine-arginine-glycine-aspartic acid-serine)- pentapeptide (which interrupts binding of RGD-containing proteins to cell surface integrins) and monoclonal antibody m7E3 (a rat β3 integrins antagonist) inhibited the effects of OPN. Inhibition of PKC using chelerythrine inhibited the activities of both MMP-2 and MMP-9. Stimulation of cells using IL-1β increased phosphorylation and translocation of PKC to membrane fractions, which was inhibited by OPN. OPN inhibited IL-1β-stimulated increases in translocation of PKC-ζ from cytosolic to membrane fractions. Furthermore, the levels of phospho-PKC-ζ were lower in the cytosolic fractions of OPN knock-out mice hearts as compared with wild type 6 days post-MI. Inhibition of PKC-ζ using PKC-ζ pseudosubstrate inhibited IL-1β-stimulated increases in MMP-2 and MMP-9 activities. These observations suggest that OPN, acting via 3 integrins, inhibits IL-1β-stimulated increases in MMP-2 and MMP-9 activity, at least in part, via the involvement of PKC-ζ. Thus, OPN may play a key role in collagen deposition during myocardial remodeling following MI by modulating cytokine-stimulated MMP activity

Quantifying sympathetic neuro-haemodynamic transduction at rest in humans:Insights into sex, ageing and blood pressure control

KEY POINTS: We have developed a simple analytical method for quantifying the transduction of sympathetic activity into vascular tone. This method demonstrates that as women age, the transfer of sympathetic nerve activity into vascular tone is increased, so that for a given level of sympathetic activity there is more vasoconstriction. In men, this measure decreases with age. Test–re‐test analysis demonstrated that the new method is a reliable estimate of sympathetic transduction. We conclude that increased sympathetic vascular coupling contributes to the age‐related increase in blood pressure that occurs in women only. This measure is a reliable estimate of sympathetic transduction in populations with high sympathetic nerve activity. Thus, it will provide information regarding whether treatment targeting the sympathetic nervous system, which interrupts the transfer of sympathetic nerve activity into vascular tone, will be effective in reducing blood pressure in hypertensive patients. This may provide insight into which populations will respond to certain types of anti‐hypertensive medication. ABSTRACT: Sex and age differences in the sympathetic control of resting blood pressure (BP) may be due to differences in the transduction of sympathetic nerve activity (SNA) into vascular tone. Current methods for dynamically quantifying transduction focus on the relationship between SNA and vasoconstriction during a pressor stimulus, which increases BP and may be contra‐indicated in patients. We describe a simple analytical method for quantifying transduction under resting conditions. We performed linear regression analysis of binned muscle SNA burst areas against diastolic BP (DBP). We assessed whether the slope of this relationship reflects the transduction of SNA into DBP. To evaluate this, we investigated whether this measure captures differences in transduction in different populations. Specifically, we (1) quantified transduction in young men (YM), young women (YW), older men (OM) and postmenopausal women (PMW); and (2) measured changes in transduction during β‐blockade using propranolol in YW, YM and PMW. YM had a greater transduction vs. OM (0.10 ± 0.01 mmHg (% s)(−1), n = 23 vs. 0.06 ± 0.01 mmHg (% s)(−1), n = 18; P = 0.003). Transduction was lowest in YW (0.02 ± 0.01 mmHg (% s)(−1), n = 23) and increased during β‐blockade (0.11 ± 0.01 mmHg (% s)(−1); P < 0.001). Transduction in PMW (0.07 ± 0.01 mmHg (% s)(−1), n = 23) was greater compared to YW (P = 0.001), and was not altered during β‐blockade (0.06 ± 0.01 mmHg (% s)(−1); P = 0.98). Importantly, transduction increased in women with age, but decreased in men. Transduction in women intersected that in men at 55 ± 1.5 years. This measure of transduction captures age‐ and sex‐differences in the sympathetic regulation of DBP and may be valuable in quantifying transduction in disease. In particular, this measure may help target treatment strategies in specific hypertensive subpopulations

Semiclassical approach to discrete symmetries in quantum chaos

We use semiclassical methods to evaluate the spectral two-point correlation function of quantum chaotic systems with discrete geometrical symmetries. The energy spectra of these systems can be divided into subspectra that are associated to irreducible representations of the corresponding symmetry group. We show that for (spinless) time reversal invariant systems the statistics inside these subspectra depend on the type of irreducible representation. For real representations the spectral statistics agree with those of the Gaussian Orthogonal Ensemble (GOE) of Random Matrix Theory (RMT), whereas complex representations correspond to the Gaussian Unitary Ensemble (GUE). For systems without time reversal invariance all subspectra show GUE statistics. There are no correlations between non-degenerate subspectra. Our techniques generalize recent developments in the semiclassical approach to quantum chaos allowing one to obtain full agreement with the two-point correlation function predicted by RMT, including oscillatory contributions.Comment: 26 pages, 8 Figure