Interactions between Connected Half-Sarcomeres Produce Emergent Mechanical Behavior in a Mathematical Model of Muscle

Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes ∼300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most ∼30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere

Anisotropic behaviors of massless Dirac fermions in graphene under periodic potential

Charge carriers of graphene show neutrino-like linear energy dispersions as well as chiral behavior near the Dirac point. Here we report highly unusual and unexpected behaviors of these carriers in applied external periodic potentials, i.e., in graphene superlattices. The group velocity renormalizes highly anisotropically even to a degree that it is not changed at all for states with wavevector in one direction but is reduced to zero in another, implying the possibility that one can make nanoscale electronic circuits out of graphene not by cutting it but by drawing on it in a non-destructive way. Also, the type of charge carrier species (e.g. electron, hole or open orbit) and their density of states vary drastically with the Fermi energy, enabling one to tune the Fermi surface-dominant properties significantly with gate voltage. These results address the fundamental question of how chiral massless Dirac fermions propagate in periodic potentials and point to a new possible path for nanoscale electronics.Comment: 10 pages, 9 figure

B Cell Depletion Reduces the Number of Autoreactive T Helper Cells and Prevents Glucose-6-Phosphate Isomerase-Induced Arthritis

The therapeutic benefit of B cell depletion in patients with rheumatoid arthritis has provided proof of concept that B cells are relevant for the pathogenesis of arthritis. It remains unknown which B cell effector functions contribute to the induction or chronification of arthritis. We studied the clinical and immunological effects of B cell depletion in glucose-6-phosphate isomerase-induced arthritis. We targeted CD22 to deplete B cells. Mice were depleted of B cells before or after immunization with glucose-6-phosphate isomerase (G6PI). The clinical and histological effects were studied. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. B cell depletion prior to G6PI-immunization prevented arthritis. B cell depletion after immunization ameliorated arthritis, whereas B cell depletion in arthritic mice was ineffective. Transfer of antibodies from arthritic mice into B cell depleted recipients did not reconstitute arthritis. B cell depleted mice harbored much fewer G6PI-specific Th cells than control animals. B cell depletion prevents but does not cure G6PI-induced arthritis. Arthritis prevention upon B cell depletion is associated with a drastic reduction in the number of G6PI-specific effector Th cells

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

Regeneration limit of classical Shannon capacity

Since Shannon derived the seminal formula for the capacity of the additive linear white Gaussian noise channel, it has commonly been interpreted as the ultimate limit of error-free information transmission rate. However, the capacity above the corresponding linear channel limit can be achieved when noise is suppressed using nonlinear elements; that is, the regenerative function not available in linear systems. Regeneration is a fundamental concept that extends from biology to optical communications. All-optical regeneration of coherent signal has attracted particular attention. Surprisingly, the quantitative impact of regeneration on the Shannon capacity has remained unstudied. Here we propose a new method of designing regenerative transmission systems with capacity that is higher than the corresponding linear channel, and illustrate it by proposing application of the Fourier transform for efficient regeneration of multilevel multidimensional signals. The regenerative Shannon limit -the upper bound of regeneration efficiency -is derived

Sex Differences in Neural Activation to Facial Expressions Denoting Contempt and Disgust

The facial expression of contempt has been regarded to communicate feelings of moral superiority. Contempt is an emotion that is closely related to disgust, but in contrast to disgust, contempt is inherently interpersonal and hierarchical. The aim of this study was twofold. First, to investigate the hypothesis of preferential amygdala responses to contempt expressions versus disgust. Second, to investigate whether, at a neural level, men would respond stronger to biological signals of interpersonal superiority (e.g., contempt) than women. We performed an experiment using functional magnetic resonance imaging (fMRI), in which participants watched facial expressions of contempt and disgust in addition to neutral expressions. The faces were presented as distractors in an oddball task in which participants had to react to one target face. Facial expressions of contempt and disgust activated a network of brain regions, including prefrontal areas (superior, middle and medial prefrontal gyrus), anterior cingulate, insula, amygdala, parietal cortex, fusiform gyrus, occipital cortex, putamen and thalamus. Contemptuous faces did not elicit stronger amygdala activation than did disgusted expressions. To limit the number of statistical comparisons, we confined our analyses of sex differences to the frontal and temporal lobes. Men displayed stronger brain activation than women to facial expressions of contempt in the medial frontal gyrus, inferior frontal gyrus, and superior temporal gyrus. Conversely, women showed stronger neural responses than men to facial expressions of disgust. In addition, the effect of stimulus sex differed for men versus women. Specifically, women showed stronger responses to male contemptuous faces (as compared to female expressions), in the insula and middle frontal gyrus. Contempt has been conceptualized as signaling perceived moral violations of social hierarchy, whereas disgust would signal violations of physical purity. Thus, our results suggest a neural basis for sex differences in moral sensitivity regarding hierarchy on the one hand and physical purity on the other

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Long-Term climate change commitment and reversibility: An EMIC intercomparison

This is the final version of the article. Available from the American Meteorological Society via the DOI in this record.This paper summarizes the results of an intercomparison project with Earth System Models of Intermediate Complexity (EMICs) undertaken in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5). The focus is on long-term climate projections designed to 1) quantify the climate change commitment of different radiative forcing trajectories and 2) explore the extent to which climate change is reversible on human time scales. All commitment simulations follow the four representative concentration pathways (RCPs) and their extensions to year 2300. MostEMICs simulate substantial surface air temperature and thermosteric sea level rise commitment following stabilization of the atmospheric composition at year-2300 levels. The meridional overturning circulation (MOC) is weakened temporarily and recovers to near-preindustrial values in most models for RCPs 2.6-6.0. The MOC weakening is more persistent for RCP8.5. Elimination of anthropogenic CO2 emissions after 2300 results in slowly decreasing atmospheric CO2 concentrations. At year 3000 atmospheric CO2 is still at more than half its year-2300 level in all EMICs forRCPs 4.5-8.5. Surface air temperature remains constant or decreases slightly and thermosteric sea level rise continues for centuries after elimination ofCO2 emissions in allEMICs.Restoration of atmosphericCO2 fromRCPto preindustrial levels over 100-1000 years requires large artificial removal of CO2 from the atmosphere and does not result in the simultaneous return to preindustrial climate conditions, as surface air temperature and sea level response exhibit a substantial time lag relative to atmospheric CO2. © 2013 American Meteorological Society.KZ and AJW acknowledge support from the National Science and Engineering Research Council (NSERC) Discovery Grant Program. AJW acknowledges support from NSERC's G8 Research Councils Initiative on Multilateral Research Funding Program. AVE and IIM were supported by the President of Russia Grant 5467.2012.5, by the Russian Foundation for Basic Research, and by the programs of the Russian Academy of Sciences. EC, TF, HG, and GPB acknowledge support from the Belgian Federal Science Policy Office. FJ, RS, and MS acknowledge support by the Swiss National Science Foundation and by the European Project CARBOCHANGE (Grant 264879), which received funding from the European Commission's Seventh Framework Programme (FP7/2007–2013). PBH and NRE acknowledge support from EU FP7 Grant ERMITAGE 265170

The predictive value of p53, p53R2, and p21 for the effect of chemoradiation therapy on oesophageal squamous cell carcinoma

The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA damage. In the present study, we analysed the expression of some p53 family proteins and their responses to chemoradiation therapy (CRT) in cases of oesophageal squamous cell carcinoma (ESCC). We immunohistochemically investigated the relationship between p53, p53R2, and p21 expression in biopsy specimens of untreated primary tumours and their clinical and histological responses to CRT in 62 patients with ESCC. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The rates of clinical and histological responses (complete or partial) to CRT were 71.0% (clinical) and 52.8% (histological). The rate of positive expression was 43.5% for p53, 37.1% for p53R2, and 54.8% for p21 expression. Statistically significant correlations were found between p53 or p53R2 expression and favourable response to CRT (P=0.0001 or 0.041 clinical, P=0.016 or 0.0018 histological, respectively). Furthermore, in p53-negative tumours, CRT was more effective in tumours with p53R2 negative expression than those with p53R2 positive expression (P=0.0014). We demonstrated that the negative expression of p53 and p53R2 expression was closely related to the effect of CRT and should predict the CRT outcome in patients with ESCC