Nonlinear behavior of shells of revolution under cyclic loading

A large deflection elastic-plastic analysis is presented, applicable to orthotropic axisymmetric plates and shells of revolution subjected to monotonic and cyclic loading conditions. The analysis is based on the finite-element method. It employs a new higher order, fully compatible, doubly curved orthotropic shell-of-revolution element using cubic Hermitian expansions for both meridional and normal displacements. Both perfectly plastic and strain hardening behavior are considered. Strain hardening is incorporated through use of the Prager-Ziegler kinematic hardening theory, which predicts an ideal Bauschinger effect. Numerous sample problems involving monotonic and cyclic loading conditions are analyzed. The monotonic results are compared with other theoretical solutions

Mapping major SARS-CoV-2 drug targets and assessment of druggability using computational fragment screening: Identification of an allosteric small-molecule binding site on the Nsp13 helicase.

The 2019 emergence of, SARS-CoV-2 has tragically taken an immense toll on human life and far reaching impacts on society. There is a need to identify effective antivirals with diverse mechanisms of action in order to accelerate preclinical development. This study focused on five of the most established drug target proteins for direct acting small molecule antivirals: Nsp5 Main Protease, Nsp12 RNA-dependent RNA polymerase, Nsp13 Helicase, Nsp16 2\u27-O methyltransferase and the S2 subunit of the Spike protein. A workflow of solvent mapping and free energy calculations was used to identify and characterize favorable small-molecule binding sites for an aromatic pharmacophore (benzene). After identifying the most favorable sites, calculated ligand efficiencies were compared utilizing computational fragment screening. The most favorable sites overall were located on Nsp12 and Nsp16, whereas the most favorable sites for Nsp13 and S2 Spike had comparatively lower ligand efficiencies relative to Nsp12 and Nsp16. Utilizing fragment screening on numerous possible sites on Nsp13 helicase, we identified a favorable allosteric site on the N-terminal zinc binding domain (ZBD) that may be amenable to virtual or biophysical fragment screening efforts. Recent structural studies of the Nsp12:Nsp13 replication-transcription complex experimentally corroborates ligand binding at this site, which is revealed to be a functional Nsp8:Nsp13 protein-protein interaction site in the complex. Detailed structural analysis of Nsp13 ZBD conformations show the role of induced-fit flexibility in this ligand binding site and identify which conformational states are associated with efficient ligand binding. We hope that this map of over 200 possible small-molecule binding sites for these drug targets may be of use for ongoing discovery, design, and drug repurposing efforts. This information may be used to prioritize screening efforts or aid in the process of deciphering how a screening hit may bind to a specific target protein

Two halves of a meaningful text are statistically different

Which statistical features distinguish a meaningful text (possibly written in an unknown system) from a meaningless set of symbols? Here we answer this question by comparing features of the first half of a text to its second half. This comparison can uncover hidden effects, because the halves have the same values of many parameters (style, genre {\it etc}). We found that the first half has more different words and more rare words than the second half. Also, words in the first half are distributed less homogeneously over the text in the sense of of the difference between the frequency and the inverse spatial period. These differences hold for the significant majority of several hundred relatively short texts we studied. The statistical significance is confirmed via the Wilcoxon test. Differences disappear after random permutation of words that destroys the linear structure of the text. The differences reveal a temporal asymmetry in meaningful texts, which is confirmed by showing that texts are much better compressible in their natural way (i.e. along the narrative) than in the word-inverted form. We conjecture that these results connect the semantic organization of a text (defined by the flow of its narrative) to its statistical features.Comment: 15 pages and 14 table

Thermoelectric Cooling at Cryogenic Temperatures

Experimental results demonstrating Peltier cooling below 10 K are reported, using crystals of the thermoelectric cerium hexaboride (CeB6). Direct measurements of the Peltier cooling showed δT up to ∼0.2 K in magnitude at T∼4–5 K. All three kinetic parameters: resistivity (ρ), heat conductivity (k), and Seebeck coefficient (S), characterizing the thermoelectric figure of merit ZT=S2T/ρk, were measured, giving high-confidence results

Glycogen synthase kinase 3, circadian rhythms, and bipolar disorder: a molecular link in the therapeutic action of lithium

BACKGROUND: Bipolar disorder (BPD) is a widespread condition characterized by recurring states of mania and depression. Lithium, a direct inhibitor of glycogen synthase kinase 3 (GSK3) activity, and a mainstay in BPD therapeutics, has been proposed to target GSK3 as a mechanism of mood stabilization. In addition to mood imbalances, patients with BPD often suffer from circadian disturbances. GSK3, an essential kinase with widespread roles in development, cell survival, and metabolism has been demonstrated to be an essential component of the Drosophila circadian clock. We sought to investigate the role of GSK3 in the mammalian clock mechanism, as a possible mediator of lithium's therapeutic effects. METHODS: GSK3 activity was decreased in mouse embryonic fibroblasts (MEFs) genetically and pharmacologically, and changes in the cyclical expression of core clock genes – mPer2 in particular – were examined. RESULTS: We demonstrate that genetic depletion of GSK3 in synchronized oscillating MEFs results in a significant delay in the periodicity of the endogenous clock mechanism, particularly in the cycling period of mPer2. Furthermore, we demonstrate that pharmacological inhibition of GSK3 activity by kenpaullone, a known antagonist of GSK3 activity, as well as by lithium, a direct inhibitor of GSK3 and the most common treatment for BPD, induces a phase delay in mPer2 transcription that resembles the effect observed with GSK3 knockdown. CONCLUSION: These results confirm GSK3 as a plausible target of lithium action in BPD therapeutics, and suggest the circadian clock mechanism as a significant modulator of lithium's clinical benefits

Laser-Powered Thermoelectric Generators Operating at Cryogenic Temperatures

A thermoelectric generator, operating in a cryostat at liquid helium temperatures, is described. Energy to the generator is supplied via an external laser beam. For this prototype device the associated heat load at permanent operation is comparable with the heat load associated with power delivery via metallic wires. Estimates indicate that still better performance can be enabled with existing thermoelectric materials, thereby far exceeding efficiency of traditional cryostat wiring. We used a prototype generator to produce electric power for measuring critical currents in Nb3Sn-films at 4K

Statistical Mechanics of Semi-Supervised Clustering in Sparse Graphs

We theoretically study semi-supervised clustering in sparse graphs in the presence of pairwise constraints on the cluster assignments of nodes. We focus on bi-cluster graphs, and study the impact of semi-supervision for varying constraint density and overlap between the clusters. Recent results for unsupervised clustering in sparse graphs indicate that there is a critical ratio of within-cluster and between-cluster connectivities below which clusters cannot be recovered with better than random accuracy. The goal of this paper is to examine the impact of pairwise constraints on the clustering accuracy. Our results suggests that the addition of constraints does not provide automatic improvement over the unsupervised case. When the density of the constraints is sufficiently small, their only impact is to shift the detection threshold while preserving the criticality. Conversely, if the density of (hard) constraints is above the percolation threshold, the criticality is suppressed and the detection threshold disappears.Comment: 8 pages, 4 figure

Two-Center Black Holes Duality-Invariants for stu Model and its lower-rank Descendants

We classify 2-center extremal black hole charge configurations through duality-invariant homogeneous polynomials, which are the generalization of the unique invariant quartic polynomial for single-center black holes based on homogeneous symmetric cubic special Kaehler geometries. A crucial role is played by an horizontal SL(p,R) symmetry group, which classifies invariants for p-center black holes. For p = 2, a (spin 2) quintet of quartic invariants emerge. We provide the minimal set of independent invariants for the rank-3 N = 2, d = 4 stu model, and for its lower-rank descendants, namely the rank-2 st^2 and rank-1 t^3 models; these models respectively exhibit seven, six and five independent invariants. We also derive the polynomial relations among these and other duality invariants. In particular, the symplectic product of two charge vectors is not independent from the quartic quintet in the t^3 model, but rather it satisfies a degree-16 relation, corresponding to a quartic equation for the square of the symplectic product itself.Comment: 1+31 pages; v2: amendments in Sec. 9, App. C added, other minor refinements, Refs. added; v3: Ref. added, typos fixed. To appear on J.Math.Phy

Optimal refrigerator

We study a refrigerator model which consists of two $n$-level systems interacting via a pulsed external field. Each system couples to its own thermal bath at temperatures $T_h$ and $T_c$, respectively ($\theta\equiv T_c/T_h<1$). The refrigerator functions in two steps: thermally isolated interaction between the systems driven by the external field and isothermal relaxation back to equilibrium. There is a complementarity between the power of heat transfer from the cold bath and the efficiency: the latter nullifies when the former is maximized and {\it vice versa}. A reasonable compromise is achieved by optimizing the product of the heat-power and efficiency over the Hamiltonian of the two system. The efficiency is then found to be bounded from below by $\zeta_{\rm CA}=\frac{1}{\sqrt{1-\theta}}-1$ (an analogue of the Curzon-Ahlborn efficiency), besides being bound from above by the Carnot efficiency $\zeta_{\rm C} = \frac{1}{1-\theta}-1$. The lower bound is reached in the equilibrium limit $\theta\to 1$. The Carnot bound is reached (for a finite power and a finite amount of heat transferred per cycle) for $\ln n\gg 1$. If the above maximization is constrained by assuming homogeneous energy spectra for both systems, the efficiency is bounded from above by $\zeta_{\rm CA}$ and converges to it for $n\gg 1$.Comment: 12 pages, 3 figure