High Speed Chaos in Optical Feedback System with Flexible Timescales

We describe a new opto-electronic device with time-delayed feedback that uses a Mach-Zehnder interferometer as passive nonlinearity and a semiconductor laser as a current-to-optical-frequency converter. Bandlimited feedback allows tuning of the characteristic time scales of both the periodic and high dimensional chaotic oscillations that can be generated with the device. Our implementation of the device produces oscillations in the frequency range of tens to hundreds of MHz. We develop a model and use it to explore the experimentally observed Andronov-Hopf bifurcation of the steady state and to estimate the dimension of the chaotic attractor.Comment: 7 pages, 6 figures, to be published in IEEE J. Quantum Electro

Controlling Fast Chaos in Delay Dynamical Systems

We introduce a novel approach for controlling fast chaos in time-delay dynamical systems and use it to control a chaotic photonic device with a characteristic time scale of ~12 ns. Our approach is a prescription for how to implement existing chaos control algorithms in a way that exploits the system's inherent time-delay and allows control even in the presence of substantial control-loop latency (the finite time it takes signals to propagate through the components in the controller). This research paves the way for applications exploiting fast control of chaos, such as chaos-based communication schemes and stabilizing the behavior of ultrafast lasers.Comment: 4 pages, 4 figures, to be published in Physical Review Letter

Controlled Quantum Secret Sharing

We present a new protocol in which a secret multiqubit quantum state $\ket{\Psi}$ is shared by $n$ players and $m$ controllers, where $\ket{\Psi}$ is the encoding state of a quantum secret sharing scheme. The players may be considered as field agents responsible for carrying out a task, using the secret information encrypted in $\ket{\Psi}$, while the controllers are superiors who decide if and when the task should be carried out and who to do it. Our protocol only requires ancillary Bell states and Bell-basis measurements.Comment: 6 pages, 0 figure, RevTeX4; published version with minor change

Data sharing: not as simple as it seems

In recent years there has been a major change on the part of funders, particularly in North America, so that data sharing is now considered to be the norm rather than the exception. We believe that data sharing is a good idea. However, we also believe that it is inappropriate to prescribe exactly when or how researchers should preserve and share data, since these issues are highly specific to each study, the nature of the data collected, who is requesting it, and what they intend to do with it. The level of ethical concern will vary according to the nature of the information, and the way in which it is collected - analyses of anonymised hospital admission records may carry a quite different ethical burden than analyses of potentially identifiable health information collected directly from the study participants. It is striking that most discussions about data sharing focus almost exclusively on issues of ownership (by the researchers or the funders) and efficiency (on the part of the funders). There is usually little discussion of the ethical issues involved in data sharing, and its implications for the study participants. Obtaining prior informed consent from the participants does not solve this problem, unless the informed consent process makes it completely clear what is being proposed, in which case most study participants would not agree. Thus, the undoubted benefits of data sharing does not remove the obligations and responsibilities that the original investigators hold for the people they invited to participate in the study

Complexity of the microglial activation pathways that drive innate host responses during lethal alphavirus encephalitis in mice

Microglia express multiple TLRs (Toll-like receptors) and provide important host defence against viruses that invade the CNS (central nervous system). Although prior studies show these cells become activated during experimental alphavirus encephalitis in mice to generate cytokines and chemokines that influence virus replication, tissue inflammation and neuronal survival, the specific PRRs (pattern recognition receptors) and signalling intermediates controlling microglial activation in this setting remain unknown. To investigate these questions directly in vivo, mice ablated of specific TLR signalling molecules were challenged with NSV (neuroadapted Sindbis virus) and CNS viral titres, inflammatory responses and clinical outcomes followed over time. To approach this problem specifically in microglia, the effects of NSV on primary cells derived from the brains of wild-type and mutant animals were characterized in vitro. From the standpoint of the virus, microglial activation required viral uncoating and an intact viral genome; inactivated virus particles did not elicit measurable microglial responses. At the level of the target cell, NSV triggered multiple PRRs in microglia to produce a broad range of inflammatory mediators via non-overlapping signalling pathways. In vivo, disease survival was surprisingly independent of TLR-driven responses, but still required production of type-I IFN (interferon) to control CNS virus replication. Interestingly, the ER (endoplasmic reticulum) protein UNC93b1 facilitated host survival independent of its known effects on endosomal TLR signalling. Taken together, these data show that alphaviruses activate microglia via multiple PRRs, highlighting the complexity of the signalling networks by which CNS host responses are elicited by these infections

Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets.

The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

What potential has tobacco control for reducing health inequalities? The New Zealand situation

In this Commentary, we aim to synthesize recent epidemiological data on tobacco and health inequalities for New Zealand and present it in new ways. We also aim to describe both existing and potential tobacco control responses for addressing these inequalities. In New Zealand smoking prevalence is higher amongst Māori and Pacific peoples (compared to those of "New Zealand European" ethnicity) and amongst those with low socioeconomic position (SEP). Consequently the smoking-related mortality burden is higher among these populations. Regarding the gap in mortality between low and high socioeconomic groups, 21% and 11% of this gap for men and women was estimated to be due to smoking in 1996–99. Regarding the gap in mortality between Māori and non-Māori/non-Pacific, 5% and 8% of this gap for men and women was estimated to be due to smoking. The estimates from both these studies are probably moderate underestimates due to misclassification bias of smoking status. Despite the modest relative contribution of smoking to these gaps, the absolute number of smoking-attributable deaths is sizable and amenable to policy and health sector responses. There is some evidence, from New Zealand and elsewhere, for interventions that reduce smoking by low-income populations and indigenous peoples. These include tobacco taxation, thematically appropriate mass media campaigns, and appropriate smoking cessation support services. But there are as yet untried interventions with major potential. A key one is for a tighter regulatory framework that could rapidly shift the nicotine market towards pharmaceutical-grade nicotine (or smokeless tobacco products) and away from smoked tobacco

Education inequalities in adult all-cause mortality: first national data for Australia using linked census and mortality data

BACKGROUND: National linked mortality and census data have not previously been available for Australia. We estimated education-based mortality inequalities from linked census and mortality data that are suitable for international comparisons. METHODS: We used the Australian Bureau of Statistics Death Registrations to Census file, with data on deaths (2011-2012) linked probabilistically to census data (linkage rate 81%). To assess validity, we compared mortality rates by age group (25-44, 45-64, 65-84 years), sex and area-inequality measures to those based on complete death registration data. We used negative binomial regression to quantify inequalities in all-cause mortality in relation to five levels of education ['Bachelor degree or higher' (highest) to 'no Year 12 and no post-secondary qualification' (lowest)], separately by sex and age group, adjusting for single year of age and correcting for linkage bias and missing education data. RESULTS: Mortality rates and area-based inequality estimates were comparable to published national estimates. Men aged 25-84 years with the lowest education had age-adjusted mortality rates 2.20 [95% confidence interval (CI): 2.08‒2.33] times those of men with the highest education. Among women, the rate ratio was 1.64 (1.55‒1.74). Rate ratios were 3.87 (3.38‒4.44) in men and 2.57 (2.15‒3.07) in women aged 25-44 years, decreasing to 1.68 (1.60‒1.76) in men and 1.44 (1.36‒1.53) in women aged 65-84 years. Absolute education inequalities increased with age. One in three to four deaths (31%) was associated with less than Bachelor level education. CONCLUSIONS: These linked national data enabled valid estimates of education inequality in mortality suitable for international comparisons. The magnitude of relative inequality is substantial and similar to that reported for other high-income countries.Rosemary J Korda, Nicholas Biddle, John Lynch, James Eynstone-Hinkins, Kay Soga, Emily Banks ... et al

Compound heterozygous RMND1 gene variants associated with chronic kidney disease, dilated cardiomyopathy and neurological involvement: a case report

Background Nuclear gene mutations are being increasingly recognised as causes of mitochondrial disease. The nuclear gene RMND1 has recently been implicated in mitochondrial disease, but the spectrum of pathogenic variants and associated phenotype for this gene, has not been fully elucidated. Case presentation An 11-month-old boy presented with renal impairment associated with a truncal ataxia, bilateral sensorineural hearing loss, hypotonia, delayed visual maturation and global developmental delay. Over a 9-year period, he progressed to chronic kidney disease stage V and developed a dilated cardiomyopathy. Abnormalities in renal and muscle biopsy as well as cytochrome c oxidase activity prompted genetic testing. After exclusion of mitochondrial DNA defects, nuclear genetic studies identified compound heterozygous RMND1 (c.713A>G, p. Asn238Ser and c.565C>T, p.Gln189*) variants. Conclusion We report RMND1 gene variants associated with end stage renal failure, dilated cardiomyopathy, deafness and neurological involvement due to mitochondrial disease. This case expands current knowledge of mitochondrial disease secondary to mutation of the RMND1 gene by further delineating renal manifestations including histopathology. To our knowledge dilated cardiomyopathy has not been reported with renal failure in mitochondrial disease due to mutations of RMND1. The presence of this complication was important in this case as it precluded renal transplantation