A Theoretical Investigation of the Drag of Generalized Aircraft Configurations in Supersonic Flow

It seems possible that, in supersonic flight, unconventional arrangements of wings and bodies may offer advantages in the form of drag reduction. It is the purpose of this report to consider the methods for determining the pressure drag for such unconventional configurations, and to consider a few of the possibilities for drag reduction in highly idealized aircraft. The idealized aircraft are defined by distributions of lift and volume in three-dimensional space, and Hayes' method of drag evaluation, which is well adapted to such problems, is the fundamental tool employed. Other methods of drag evaluation are considered also wherever they appear to offer amplifications. The basic singularities such as sources, dipoles, lifting elements and volume elements are discussed, and some of the useful inter-relations between these elements are presented. Hayes' method of drag evaluation is derived in detail starting with the general momentum theorem. In going from planar systems to spatial systems certain new problems arise. For example, interference between lift and thickness distributions generally appears, and such effects are used to explain the difference between the non-zero wave drag of Sears-Haack bodies and the zero wave drag of Ferrari's ring wing plus central body. Another new feature of the spatial systems is that optimum configurations generally are not unique, there being an infinite family of lift or thickness distributions producing the same minimum drag. However it is shown that all members of an optimum family produce the same flow field in a certain region external to the singularity distribution. Other results of the study indicate that certain spatial distributions may produce materially less wave drag and vortex drag than comparable planar systems. It is not at all certain that such advantages can be realized in practical aircraft designs, but further investigation seems to be warranted

The self-consistent gravitational self-force

I review the problem of motion for small bodies in General Relativity, with an emphasis on developing a self-consistent treatment of the gravitational self-force. An analysis of the various derivations extant in the literature leads me to formulate an asymptotic expansion in which the metric is expanded while a representative worldline is held fixed; I discuss the utility of this expansion for both exact point particles and asymptotically small bodies, contrasting it with a regular expansion in which both the metric and the worldline are expanded. Based on these preliminary analyses, I present a general method of deriving self-consistent equations of motion for arbitrarily structured (sufficiently compact) small bodies. My method utilizes two expansions: an inner expansion that keeps the size of the body fixed, and an outer expansion that lets the body shrink while holding its worldline fixed. By imposing the Lorenz gauge, I express the global solution to the Einstein equation in the outer expansion in terms of an integral over a worldtube of small radius surrounding the body. Appropriate boundary data on the tube are determined from a local-in-space expansion in a buffer region where both the inner and outer expansions are valid. This buffer-region expansion also results in an expression for the self-force in terms of irreducible pieces of the metric perturbation on the worldline. Based on the global solution, these pieces of the perturbation can be written in terms of a tail integral over the body's past history. This approach can be applied at any order to obtain a self-consistent approximation that is valid on long timescales, both near and far from the small body. I conclude by discussing possible extensions of my method and comparing it to alternative approaches.Comment: 44 pages, 4 figure

Trade-offs between morphology and thermal niches mediate adaptation in response to competing selective pressures

The effects of climate change—such as increased temperature variability and novel predators—rarely happen in isolation, but it is unclear how organisms cope with mul- tiple stressors simultaneously. To explore this, we grew replicate Paramecium caudatum populations in either constant or variable temperatures and exposed half to predation. We then fit thermal performance curves (TPCs) of intrinsic growth rate (rmax) for each replicate population (N = 12) across seven temperatures (10°C–38°C). TPCs of P. caudatum exposed to both temperature variability and predation re- sponded only to one or the other (but not both), resulting in unpredictable outcomes. These changes in TPCs were accompanied by changes in cell morphology. Although cell volume was conserved across treatments, cells became narrower in response to temperature variability and rounder in response to predation. Our findings sug- gest that predation and temperature variability produce conflicting pressures on both thermal performance and cell morphology. Lastly, we found a strong correlation between changes in cell morphology and TPC parameters in response to predation, suggesting that responses to opposing selective pressures could be constrained by trade-offs. Our results shed new light on how environmental and ecological pressures interact to elicit changes in characteristics at both the individual and population levels. We further suggest that morphological responses to interactive environmen- tal forces may modulate population-level responses, making prediction of long-term responses to environmental change challenging

Trade-Offs Between Morphology and Thermal Niches Mediate Adaptation in Response to Competing Selective Pressures

Abstract The effects of climate change—such as increased temperature variability and novel predators—rarely happen in isolation, but it is unclear how organisms cope with multiple stressors simultaneously. To explore this, we grew replicate Paramecium caudatum populations in either constant or variable temperatures and exposed half to predation. We then fit thermal performance curves (TPCs) of intrinsic growth rate (rmax) for each replicate population (N = 12) across seven temperatures (10°C–38°C). TPCs of P. caudatum exposed to both temperature variability and predation responded only to one or the other (but not both), resulting in unpredictable outcomes. These changes in TPCs were accompanied by changes in cell morphology. Although cell volume was conserved across treatments, cells became narrower in response to temperature variability and rounder in response to predation. Our findings suggest that predation and temperature variability produce conflicting pressures on both thermal performance and cell morphology. Lastly, we found a strong correlation between changes in cell morphology and TPC parameters in response to predation, suggesting that responses to opposing selective pressures could be constrained by trade-offs. Our results shed new light on how environmental and ecological pressures interact to elicit changes in characteristics at both the individual and population levels. We further suggest that morphological responses to interactive environmental forces may modulate population-level responses, making prediction of long-term responses to environmental change challenging

The glycine receptor alpha 3 subunit mRNA expression shows sex-dependent differences in the adult mouse brain

BackgroundThe glycinergic system plays an important inhibitory role in the mouse central nervous system, where glycine controls the excitability of spinal itch- and pain-mediating neurons. Impairments of the glycine receptors can cause motor and sensory deficits. Glycine exerts inhibition through interaction with ligand-gated ion channels composed of alpha and beta subunits. We have investigated the mRNA expression of the glycine receptor alpha 3 (Glra3) subunit in the nervous system as well as in several peripheral organs of female and male mice.ResultsSingle-cell RNA sequencing (scRNA-seq) data analysis on the Zeisel et al. (2018) dataset indicated widespread but low expression of Glra3 in vesicular glutamate transporter 2 (Vglut2, Slc17a6) positive and vesicular inhibitory amino acid transporter (Viaat, Slc32a1)positive neurons of the mouse central nervous system. Highest occurrence of Glra3 expression was identified in the cortex, amygdala, and striatal regions, as well as in the hypothalamus, brainstem and spinal cord. Bulk quantitative real-time-PCR (qRT-PCR) analysis demonstrated Glra3 expression in cortex, amygdala, striatum, hypothalamus, thalamus, pituitary gland, hippocampus, cerebellum, brainstem, and spinal cord. Additionally, male mice expressed higher levels of Glra3 in all investigated brain areas compared with female mice. Lastly, RNAscope spatially validated Glra3 expression in the areas indicated by the single-cell and bulk analyses. Moreover, RNAscope analysis confirmed co-localization of Glra3 with Slc17a6 or Slc32a1 in the central nervous system areas suggested from the single-cell data.ConclusionsGlra3 expression is low but widespread in the mouse central nervous system. Clear sex-dependent differences have been identified, indicating higher levels of Glra3 in several telencephalic and diencephalic areas, as well as in cerebellum and brainstem, in male mice compared with female mice

Probing the role of the cation–π interaction in the binding sites of GPCRs using unnatural amino acids

We describe a general application of the nonsense suppression methodology for unnatural amino acid incorporation to probe drug–receptor interactions in functional G protein-coupled receptors (GPCRs), evaluating the binding sites of both the M2 muscarinic acetylcholine receptor and the D2 dopamine receptor. Receptors were expressed in Xenopus oocytes, and activation of a G protein-coupled, inward-rectifying K^+ channel (GIRK) provided, after optimization of conditions, a quantitative readout of receptor function. A number of aromatic amino acids thought to be near the agonist-binding site were evaluated. Incorporation of a series of fluorinated tryptophan derivatives at W6.48 of the D2 receptor establishes a cation–π interaction between the agonist dopamine and W6.48, suggesting a reorientation of W6.48 on agonist binding, consistent with proposed “rotamer switch” models. Interestingly, no comparable cation–π interaction was found at the aligning residue in the M2 receptor

Equation level matching: An extension of the method of matched asymptotic expansion for problems of wave propagation

We introduce an alternative to the method of matched asymptotic expansions. In the "traditional" implementation, approximate solutions, valid in different (but overlapping) regions are matched by using "intermediate" variables. Here we propose to match at the level of the equations involved, via a "uniform expansion" whose equations enfold those of the approximations to be matched. This has the advantage that one does not need to explicitly solve the asymptotic equations to do the matching, which can be quite impossible for some problems. In addition, it allows matching to proceed in certain wave situations where the traditional approach fails because the time behaviors differ (e.g., one of the expansions does not include dissipation). On the other hand, this approach does not provide the fairly explicit approximations resulting from standard matching. In fact, this is not even its aim, which to produce the "simplest" set of equations that capture the behavior

Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren

<STRONG>Background</STRONG> Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation. <STRONG>Methods and Findings</STRONG> We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37–39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12–1.20; 33–36 wk adjusted OR 1.53, 95% CI 1.43–1.63; 28–32 wk adjusted OR 2.66, 95% CI 2.38–2.97; 24–27 wk adjusted OR 6.92, 95% CI 5.58–8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37–39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases. <STRONG>Conclusions</STRONG> Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range