Reliability Analysis of Concurrent Systems using LTSA

The analysis for software dependability is considered an important task within the software engineering life cycle. However, it is often impossible to carry out this task due to the complexity of available tools, lack of expert personnel and time-to-market pressures. As a result, released software versions may present unverified dependability properties subjecting customers to blind software reliability assessment. In particular, concurrent systems present certain behaviour that require a more complex system analysis not easily grasped at system design and architecture level

Locomotor adaptability in persons with unilateral transtibial amputation

Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb

Quantification of the performance of chaotic micromixers on the basis of finite time Lyapunov exponents

Chaotic micromixers such as the staggered herringbone mixer developed by Stroock et al. allow efficient mixing of fluids even at low Reynolds number by repeated stretching and folding of the fluid interfaces. The ability of the fluid to mix well depends on the rate at which "chaotic advection" occurs in the mixer. An optimization of mixer geometries is a non trivial task which is often performed by time consuming and expensive trial and error experiments. In this paper an algorithm is presented that applies the concept of finite-time Lyapunov exponents to obtain a quantitative measure of the chaotic advection of the flow and hence the performance of micromixers. By performing lattice Boltzmann simulations of the flow inside a mixer geometry, introducing massless and non-interacting tracer particles and following their trajectories the finite time Lyapunov exponents can be calculated. The applicability of the method is demonstrated by a comparison of the improved geometrical structure of the staggered herringbone mixer with available literature data.Comment: 9 pages, 8 figure

Behavioural syndrome in a solitary predator is independent of body size and growth rate.

Models explaining behavioural syndromes often focus on state-dependency, linking behavioural variation to individual differences in other phenotypic features. Empirical studies are, however, rare. Here, we tested for a size and growth-dependent stable behavioural syndrome in the juvenile-stages of a solitary apex predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk. Pike swimming activity, latency to prey attack, number of successful and unsuccessful prey attacks was measured during the presence/absence of visual contact with a competitor or predator. Foraging behaviour across risks was considered an appropriate indicator of boldness in this solitary predator where a trade-off between foraging behaviour and threat avoidance has been reported. Support was found for a behavioural syndrome, where the rank order differences in the foraging behaviour between individuals were maintained across time and risk situation. However, individual behaviour was independent of body size and growth in conditions of high food availability, showing no evidence to support the state-dependent personality hypothesis. The importance of a combination of spatial and temporal environmental variation for generating growth differences is highlighted

Aspects of holography for theories with hyperscaling violation

We analyze various aspects of the recently proposed holographic theories with general dynamical critical exponent z and hyperscaling violation exponent $\theta$. We first find the basic constraints on $z, \theta$ from the gravity side, and compute the stress-energy tensor expectation values and scalar two-point functions. Massive correlators exhibit a nontrivial exponential behavior at long distances, controlled by $\theta$. At short distance, the two-point functions become power-law, with a universal form for $\theta > 0$. Next, the calculation of the holographic entanglement entropy reveals the existence of novel phases which violate the area law. The entropy in these phases has a behavior that interpolates between that of a Fermi surface and that exhibited by systems with extensive entanglement entropy. Finally, we describe microscopic embeddings of some $\theta \neq 0$ metrics into full string theory models -- these metrics characterize large regions of the parameter space of Dp-brane metrics for $p\neq 3$. For instance, the theory of N D2-branes in IIA supergravity has z=1 and $\theta = -1/3$ over a wide range of scales, at large $g_s N$.Comment: 35 pages; v2: new references added; v3: proper reference [14] added; v4: minor clarification

Regulatory control and the costs and benefits of biochemical noise

Experiments in recent years have vividly demonstrated that gene expression can be highly stochastic. How protein concentration fluctuations affect the growth rate of a population of cells, is, however, a wide open question. We present a mathematical model that makes it possible to quantify the effect of protein concentration fluctuations on the growth rate of a population of genetically identical cells. The model predicts that the population's growth rate depends on how the growth rate of a single cell varies with protein concentration, the variance of the protein concentration fluctuations, and the correlation time of these fluctuations. The model also predicts that when the average concentration of a protein is close to the value that maximizes the growth rate, fluctuations in its concentration always reduce the growth rate. However, when the average protein concentration deviates sufficiently from the optimal level, fluctuations can enhance the growth rate of the population, even when the growth rate of a cell depends linearly on the protein concentration. The model also shows that the ensemble or population average of a quantity, such as the average protein expression level or its variance, is in general not equal to its time average as obtained from tracing a single cell and its descendants. We apply our model to perform a cost-benefit analysis of gene regulatory control. Our analysis predicts that the optimal expression level of a gene regulatory protein is determined by the trade-off between the cost of synthesizing the regulatory protein and the benefit of minimizing the fluctuations in the expression of its target gene. We discuss possible experiments that could test our predictions.Comment: Revised manuscript;35 pages, 4 figures, REVTeX4; to appear in PLoS Computational Biolog

IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

Deterministic polarization chaos from a laser diode

Fifty years after the invention of the laser diode and fourty years after the report of the butterfly effect - i.e. the unpredictability of deterministic chaos, it is said that a laser diode behaves like a damped nonlinear oscillator. Hence no chaos can be generated unless with additional forcing or parameter modulation. Here we report the first counter-example of a free-running laser diode generating chaos. The underlying physics is a nonlinear coupling between two elliptically polarized modes in a vertical-cavity surface-emitting laser. We identify chaos in experimental time-series and show theoretically the bifurcations leading to single- and double-scroll attractors with characteristics similar to Lorenz chaos. The reported polarization chaos resembles at first sight a noise-driven mode hopping but shows opposite statistical properties. Our findings open up new research areas that combine the high speed performances of microcavity lasers with controllable and integrated sources of optical chaos.Comment: 13 pages, 5 figure

Broadband random optoelectronic oscillator

[EN] Random scattering of light in transmission media has attracted a great deal of attention in the field of photonics over the past few decades. An optoelectronic oscillator (OEO) is a microwave photonic system offering unbeatable features for the generation of microwave oscillations with ultra-low phase noise. Here, we combine the unique features of random scattering and OEO technologies by proposing an OEO structure based on random distributed feedback. Thanks to the random distribution of Rayleigh scattering caused by inhomogeneities within the glass structure of the fiber, we demonstrate the generation of ultra-wideband (up to 40¿GHz from DC) random microwave signals in an open cavity OEO. The generated signals enjoy random characteristics, and their frequencies are not limited by a fixed cavity length figure. The proposed device has potential in many fields such as random bit generation, radar systems, electronic interference and countermeasures, and telecommunications.Thanks N. Shi and Y. Yang for comments and discussion. This work was supported by the National Key Research and Development Program of China under 2018YFB2201902 and the National Natural Science Foundation of China under 61925505. This work was also partly supported by the National Key Research and Development Program of China under 2018YFB2201901, 2018YFB2201903, and the National Natural Science Foundation of China under 61535012 and 61705217.Ge, Z.; Hao, T.; Capmany Francoy, J.; Li, W.; Zhu, N.; Li, M. (2020). Broadband random optoelectronic oscillator. Nature Communications. 11(1):1-8. https://doi.org/10.1038/s41467-020-19596-xS18111Feng, S., Kane, C., Lee, P. A. & Stone, A. D. Correlations and fluctuations of coherent wave transmission through disordered media. Phys. Rev. Lett. 61, 834 (1988).Wiersma, D. S. & Cavalieri, S. Light emission: a temperature-tunable random laser. Nature 414, 708 (2001).Wiersma, D. S. The physics and applications of random lasers. Nat. Phys. 4, 359 (2008).Turitsyn, S. K. et al. Random distributed feedback fibre laser. Nat. Photonics 4, 231–235 (2010).Babin, S. A., El-Taher, A. E., Harper, P., Podivilov, E. V. & Turitsyn, S. K. Tunable random fiber laser. Phys. Rev. A 84, 021805 (2011).Turitsyn, S. K. et al. Random distributed feedback fibre lasers. Phys. Rep. 542, 133–193 (2014).Barnoski, M., Rourke, M., Jensen, S. M. & Melville, R. T. Optical time domain reflectometer. Appl. Opt. 16, 2375–2379 (1977).Yao, X. S. & Maleki, L. Optoelectronic microwave oscillator. JOSA B 13, 1725–1735 (1996).Maleki, L. Sources: the optoelectronic oscillator. Nat. Photonics 5, 728 (2011).Yao, X. S. & Maleki, L. Multiloop optoelectronic oscillator. IEEE J. Quantum Electron 36, 79–84 (2000).Hao, T. et al. Breaking the limitation of mode building time in an optoelectronic oscillator. Nat. Commun. 9, 1839 (2018).Zhang, W. & Yao, J. Silicon photonic integrated optoelectronic oscillator for frequency-tunable microwave generation. J. Lightwave Technol. 36, 4655–4663 (2018).Hao, T. et al. Toward Monolithic Integration of OEOs: from systems to chips. J. Lightwave Technol. 36, 4565–4582 (2018).Zhang, J. & Yao, J. Parity-time–symmetric optoelectronic oscillator. Sci. Adv. 4, eaar6782 (2018).Liu, Y. et al. Observation of parity-time symmetry in microwave photonics. Light Sci. Appl. 7, 38 (2018).Nakazawa, M. Rayleigh backscattering theory for single-mode optical fibers. JOSA 73, 1175–1180 (1983).Hartog, A. & Gold, M. On the theory of backscattering in single-mode optical fibers. J. Lightwave Technol. 2, 76–82 (1984).Eickhoff, W., & Ulrich, R. Statistics of backscattering in single-mode fiber. In Optical Fiber Communication Conference. Optical Society of America (1981).Alekseev, A. E., Tezadov, Y. A. & Potapov, V. T. Statistical properties of backscattered semiconductor laser radiation with different degrees of coherence. Quantum Electron 42, 76–81 (2012).Gysel, P. & Staubli, R. K. Statistical properties of Rayleigh backscattering in single-mode fibers. J. Lightwave Technol. 8, 561–567 (1990).Staubli, R. K. & Gysel, P. Statistical properties of single-mode fiber rayleigh backscattered intensity and resulting detector current. IEEE Trans. Commun. 40, 1091–1097 (1992).Levy, E. C., Horowitz, M. & Menyuk, C. R. Modeling optoelectronic oscillators. JOSA B 26, 148–159 (2009).Yariv, A. Introduction to Optical Electronics 2nd edn. (Holt, Rinehart and Winston, New York, 1976).Aoki, Y., Tajima, K. & Mito, I. Input power limits of single-mode optical fibers due to stimulated Brillouin scattering in optical communication systems. J. Lightwave Technol. 6, 710–719 (1988).Song, H. J., Shimizu, N., Kukutsu, N., Nagatsuma, T. & Kado, Y. Microwave photonic noise source from microwave to sub-terahertz wave bands and its applications to noise characterization. IEEE Trans. Microw. Theory Tech. 56, 2989–2997 (2008).Chembo, Y. K., et al. Optoelectronic oscillators with time-delayed feedback. Rev. Mod. Phys. 91, 035006 (2019).Callan, K. E. et al. Broadband chaos generated by an optoelectronic oscillator. Phys. Rev. Lett. 104, 113901 (2010).Lavrov, R. et al. Electro-optic delay oscillator with nonlocal nonlinearity: Optical phase dynamics, chaos, and synchronization. Phys. Rev. E. 80, 026207 (2009).Wolf, A., Swift, J. B., Swinney, H. L. & Vastano, J. A. Determining Lyapunov exponents from a time series. Phys. D. 16, 285–317 (1985).Grassberger, P. & Procaccia, I. Characterization of strange attractors. Phys. Rev. Lett. 50, 346 (1983).Grassberger, P. & Procaccia, I. Measuring the strangeness of strange attractors. Phys. D. 9, 189–208 (1983).Romeira, B. et al. Broadband chaotic signals and breather oscillations in an optoelectronic oscillator incorporating a microwave photonic filter. J. Lightwave Technol. 32, 3933–3942 (2014)

Association with Aurora-A controls N-MYC-dependent promoter escape and pause release of RNA polymerase II during the cell cycle

MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II). To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes in neuroblastoma cells. The analysis shows that N-MYC forms complexes with TFIIIC, TOP2A, and RAD21, a subunit of cohesin. N-MYC and TFIIIC bind to overlapping sites in thousands of Pol II promoters and intergenic regions. TFIIIC promotes association of RAD21 with N-MYC target sites and is required for N-MYC-dependent promoter escape and pause release of Pol II. Aurora-A competes with binding of TFIIIC and RAD21 to N-MYC in vitro and antagonizes association of TOP2A, TFIIIC, and RAD21 with N-MYC during S phase, blocking N-MYC-dependent release of Pol II from the promoter. Inhibition of Aurora-A in S phase restores RAD21 and TFIIIC binding to chromatin and partially restores N-MYC-dependent transcriptional elongation. We propose that complex formation with Aurora-A controls N-MYC function during the cell cycle