Silicon-chip-based ultrafast optical oscilloscope

With the realization of faster telecommunication data rates and an expanding interest in ultrafast chemical and physical phenomena, it has become important to develop techniques that enable simple measurements of optical waveforms with subpicosecond resolution. State-of-the-art oscilloscopes with high-speed photodetectors provide single-shot waveform measurement with 30-ps resolution. Although multiple-shot sampling techniques can achieve few-picosecond resolution, single-shot measurements are necessary to analyse events that are rapidly varying in time, asynchronous, or may occur only once. Further improvements in single-shot resolution are challenging, owing to microelectronic bandwidth limitations. To overcome these limitations, researchers have looked towards all-optical techniques because of the large processing bandwidths that photonics allow. This has generated an explosion of interest in the integration of photonics on standard electronics platforms, which has spawned the field of silicon photonics and promises to enable the next generation of computer processing units and advances in high-bandwidth communications. For the success of silicon photonics in these areas, on-chip optical signal-processing for optical performance monitoring will prove critical. Beyond next-generation communications, silicon-compatible ultrafast metrology would be of great utility to many fundamental research fields, as evident from the scientific impact that ultrafast measurement techniques continue to make. Here, using time-to-frequency conversion via the nonlinear process of four-wave mixing on a silicon chip, we demonstrate a waveform measurement technology within a silicon-photonic platform. We measure optical waveforms with 220-fs resolution over lengths greater than 100 ps, which represent the largest record-length-to-resolution ratio (>450) of any single-shot-capable picosecond waveform measurement technique. Our implementation allows for single-shot measurements and uses only highly developed electronic and optical materials of complementary metal-oxide-semiconductor (CMOS)-compatible silicon-on-insulator technology and single-mode optical fibre. The mature silicon-on-insulator platform and the ability to integrate electronics with these CMOS-compatible photonics offer great promise to extend this technology into commonplace bench-top and chip-scale instruments.     

Robotics: self-reproducing machines

Self-reproduction is central to biological life for long-term sustainability and evolutionary adaptation. Although these traits would also be desirable in many engineered systems, the principles of self-reproduction have not been exploited in machine design. Here we create simple machines that act as autonomous modular robots and are capable of physical self-reproduction using a set of cubes.     

Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein

The distribution of fitness effects of protein mutations is still unknown. Of particular interest is whether accumulating deleterious mutations interact, and how the resulting epistatic effects shape the protein's fitness landscape. Here we apply a model system in which bacterial fitness correlates with the enzymatic activity of TEM-1 beta-lactamase (antibiotic degradation). Subjecting TEM-1 to random mutational drift and purifying selection (to purge deleterious mutations) produced changes in its fitness landscape indicative of negative epistasis; that is, the combined deleterious effects of mutations were, on average, larger than expected from the multiplication of their individual effects. As observed in computational systems, negative epistasis was tightly associated with higher tolerance to mutations (robustness). Thus, under a low selection pressure, a large fraction of mutations was initially tolerated (high robustness), but as mutations accumulated, their fitness toll increased, resulting in the observed negative epistasis. These findings, supported by FoldX stability computations of the mutational effects, prompt a new model in which the mutational robustness (or neutrality) observed in proteins, and other biological systems, is due primarily to a stability margin, or threshold, that buffers the deleterious physico-chemical effects of mutations on fitness. Threshold robustness is inherently epistatic-once the stability threshold is exhausted, the deleterious effects of mutations become fully pronounced, thereby making proteins far less robust than generally assumed.     

Broad-band optical parametric gain on a silicon photonic chip

Developing an optical amplifier on silicon is essential for the success of silicon-on-insulator (SOI) photonic integrated circuits. Recently, optical gain with a 1-nm bandwidth was demonstrated using the Raman effect, which led to the demonstration of a Raman oscillator, lossless optical modulation and optically tunable slow light. A key strength of optical communications is the parallelism of information transfer and processing onto multiple wavelength channels. However, the relatively narrow Raman gain bandwidth only allows for amplification or generation of a single wavelength channel. If broad gain bandwidths were to be demonstrated on silicon, then an array of wavelength channels could be generated and processed, representing a critical advance for densely integrated photonic circuits. Here we demonstrate net on/off gain over a wavelength range of 28 nm through the optical process of phase-matched four-wave mixing in suitably designed SOI channel waveguides. We also demonstrate wavelength conversion in the range 1,511-1,591 nm with peak conversion efficiencies of +5.2 dB, which represents more than 20 times improvement on previous four-wave-mixing efficiencies in SOI waveguides. These advances allow for the implementation of dense wavelength division multiplexing in an all-silicon photonic integrated circuit. Additionally, all-optical delays, all-optical switches, optical signal regenerators and optical sources for quantum information technology, all demonstrated using four-wave mixing in silica fibres, can now be transferred to the SOI platform.     

Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.     

The induction of blood platelet aggregation by divalent cations

Zusammenfassung Im blutplättchenhaltigen Plasma wurden die Thrombozyten durch Nickel, Zink, Mangan, Kalzium, Magnesium und Strontium aggregiert, wobei Nickel die stärkste Wirkung hatte. Adenosin-Analoga und Antiserotonin unterdrückten den Effekt, was durch die Freisetzung von ADP und Serotonin aus den Thrombozyten bedingt zu sein scheint.     

Automatic design and manufacture of robotic lifeforms

Biological life is in control of its own means of reproduction, which generally involves complex, autocatalysing chemical reactions. But this autonomy of design and manufacture has not yet been realized artificially. Robots are still laboriously designed and constructed by teams of human engineers, usually at considerable expense. Few robots are available because these costs must be absorbed through mass production, which is justified only for toys, weapons and industrial systems such as automatic teller machines. Here we report the results of a combined computational and experimental approach in which simple electromechanical systems are evolved through simulations from basic building blocks (bars, actuators and artificial neurons); the 'fittest' machines (defined by their locomotive ability) are then fabricated robotically using rapid manufacturing technology. We thus achieve autonomy of design and construction using evolution in a 'limited universe' physical simulation coupled to automatic fabrication.     

Gold nanoparticles induce nuclear damage in breast cancer cells,which is further amplified by hyperthermia

Gold nanoparticles have emerged as promising tools for cancer research and therapy, where they can promote thermal killing. The molecular mechanisms underlying these events are not fully understood. The geometry and size of gold nanoparticles can determine the severity of cellular damage. Therefore, small and big gold nanospheres as well as gold nanoflowers were evaluated side-by-side. To obtain quantitative data at the subcellular and molecular level, we assessed how gold nanoparticles, either alone or in combination with mild hyperthermia, altered the physiology of cultured human breast cancer cells. Our analyses focused on the nucleus, because this organelle is essential for cell survival. We showed that all the examined gold nanoparticles associated with nuclei. However, their biological effects were quantitatively different. Thus, depending on the shape and size, gold nanoparticles changed multiple nuclear parameters. They redistributed stress-sensitive regulators of nuclear biology, altered the nuclear morphology, reorganized nuclear laminae and envelopes, and inhibited nucleolar functions. In particular, gold nanoparticles reduced the de novo biosynthesis of RNA in nucleoli, the subnuclear compartments that produce ribosomes. While small gold nanospheres and nanoflowers, but not big gold nanospheres, damaged the nucleus at normal growth temperature, several of these defects were further exacerbated by mild hyperthermia. Taken together, the toxicity of gold nanoparticles correlated with changes in nuclear organization and function. These results emphasize that the cell nucleus is a prominent target for gold nanoparticles of different morphologies. Moreover, we demonstrated that RNA synthesis in nucleoli provides quantitative information on nuclear damage and cancer cell survival.