Low-energy, high-performance lossless 8×8 SOA switch

We demonstrate the first monolithically-integrated active-passive lossless 8×8 SOA switch. A wide IPDR of 14.5dB for penalty <1dB is achieved. The switch paths through the device exhibit excellent uniformity.The research leading to these results has received funding from the UK EPSRC through the INTERNET, STAR and COPOS II grants and the European Commission under FP7 grant agreement ICT 257210 PARADIGM.This is the accepted manuscript. The final version is available from OSA at http://www.opticsinfobase.org/abstract.cfm?uri=OFC-2015-Th4E.6

Advanced photonic routing sub-systems with efficient routing control

In recent years, there has been much interest in the development of optical switches which can route optical signals from different input guides to different outputs based on thermo-optic and electro-optic technologies. Such switches, which can be reconfigured on millisecond and microsecond timescales, have already attracted commercial interest. However switches which are able to reconfigure on the nanosecond timescales required for packet switching have been more challenging and only in recent years, have router concepts been devised to allow lossless routers to be constructed able to switch on nanosecond timescales with more than 16×16 ports. This paper will therefore review the advances that have occurred to allow such operation and then describe recent studies that have begun to determine the electronic control and functionality required to enable full and practical operation of such switches in high performance networks.This research has received funding from the UK Engineering and Physical Sciences Research Council through the INTERNET Project, STAR and COPOS II grants and the European Commission under FP7 grant agreement ICT 257210 PARADIGM.This is the author accepted manuscript. The final version is available from IEEE via http://dx.doi.org/10.1109/ICTON.2015.719339

Demonstration of the feasibility of large-port-count optical switching using a hybrid Mach-Zehnder interferometer-semiconductor optical amplifier switch module in a recirculating loop.

For what we believe is the first time, the feasibility of large-port-count nanosecond-reconfiguration-time optical switches is demonstrated using a hybrid approach, where Mach-Zehnder interferometric (MZI) switches provide low-loss, high-speed routing with short semiconductor optical amplifiers (SOAs) being integrated to enhance extinction. By repeatedly passing signals through a monolithic hybrid dilated 2×2 switch module in a recirculating loop, the potential performance of high-port-count switches using the hybrid approach is demonstrated. Experimentally, a single pass switch penalty of only 0.1 dB is demonstrated for the 2×2 module, while even after seven passes through the switch, equivalent to a 128×128 router, a penalty of only 2.4 dB is recorded at a data rate of 10 Gb/s.This is the author accepted manuscript. The final version is published in Optics Letters - http://www.opticsinfobase.org/ol/abstract.cfm?uri=ol-39-18-5244

Low latency optical switch for high performance computing with minimized processor energy load [Invited]

Power density and cooling issues are limiting the performance of high performance chip multiprocessors (CMPs), and off-chip communications currently consume more than 20% of power for memory, coherence, PCI, and Ethernet links. Photonic transceivers integrated with CMPs are being developed to overcome these issues, potentially allowing low hop count switched connections between chips or data center servers. However, latency in setting up optical connections is critically important in all computing applications, and having transceivers integrated on the processor chip also pushes other network functions and their associated power consumption onto the chip. In this paper, we propose a low latency optical switch architecture that minimizes the power consumed on the processor chip for two scenarios: multiple-socket shared memory coherence networks and optical top-of-rack switches for data centers. The switch architecture reduces power consumed on the CMP using a control plane with a simplified send and forget server interface and the use of a hybrid Mach–Zehnder interferometer and semiconductor optical amplifier integrated optical switch with electronic buffering. Results show that the proposed architecture offers a 42% reduction in head latency at low loads compared with a conventional scheduled optical switch as well as offering increased performance for streaming and incast traffic patterns. Power dissipated on the server chip is shown to be reduced by more than 60% compared with a scheduled optical switch architecture with ring resonator switching.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) INTERNET program grant and an EPSRC Fellowship grant to Philip Watts. Both University College London and the University of Cambridge are members of GreenTouch.This paper was published in the Journal of Optical Communications and Networking and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/jocn/abstract.cfm?uri=jocn-7-3-A498. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law. This is the accepted manuscript of a paper published in the Journal of Optical Communications and Networking, Vol. 7, Issue 3, pp. A498-A510 (2015) http://dx.doi.org/10.1364/JOCN.7.00A49

Casimir effect of electromagnetic field in Randall-Sundrum spacetime

We study the finite temperature Casimir effect on a pair of parallel perfectly conducting plates in Randall-Sundrum model without using scalar field analogy. Two different ways of interpreting perfectly conducting conditions are discussed. The conventional way that uses perfectly conducting condition induced from 5D leads to three discrete mode corrections. This is very different from the result obtained from imposing 4D perfectly conducting conditions on the 4D massless and massive vector fields obtained by decomposing the 5D electromagnetic field. The latter only contains two discrete mode corrections, but it has a continuum mode correction that depends on the thicknesses of the plates. It is shown that under both boundary conditions, the corrections to the Casimir force make the Casimir force more attractive. The correction under 4D perfectly conducting condition is always smaller than the correction under the 5D induced perfectly conducting condition. These statements are true at any temperature.Comment: 20 pages, 4 figure

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells

Glutaminase, which converts glutamine to glutamate, is involved in Warburg effect in cancer cells. Two human glutaminase genes have been identified, GLS (GLS1) and GLS2. Two alternative transcripts arise from each glutaminase gene: first, the kidney isoform (KGA) and glutaminase C (GAC) for GLS; and, second, the liver isoform (LGA) and glutaminase B (GAB) for GLS2. While GLS1 is considered as a cancer therapeutic target, the potential role of GLS2 in cancer remains unclear. Here, we discovered a series of alkyl benzoquinones that preferentially inhibit glutaminase B isoform (GAB, GLS2) rather than the kidney isoform of glutaminase (KGA, GLS1). We identified amino acid residues in an allosteric binding pocket responsible for the selectivity. Treatment with the alkyl benzoquinones decreased intracellular glutaminase activity and glutamate levels. GLS2 inhibition by either alkyl benzoquinones or GLS2 siRNA reduced carcinoma cell proliferation and anchorage-independent colony formation, and induced autophagy via AMPK mediated mTORC1 inhibition. Our findings demonstrate amino acid sequences for selective inhibition of glutaminase isozymes and validate GLS2 as a potential anti-cancer target

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

Jugular venous reflux and brain parenchyma volumes in elderly patients with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. RESULTS: JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR-positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). CONCLUSIONS: JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema

Differential lipid dependence of the function of bacterial sodium channels

The lipid bilayer is important for maintaining the integrity of cellular compartments and plays a vital role in providing the hydrophobic and charged interactions necessary for membrane protein structure, conformational flexibility and function. To directly assess the lipid dependence of activity for voltage-gated sodium channels, we compared the activity of three bacterial sodium channel homologues (NaChBac, NavMs, and NavSp) by cumulative 22Na+ uptake into proteoliposomes containing a 3:1 ratio of 1-palmitoyl 2-oleoyl phosphatidylethanolamine and different “guest” glycerophospholipids. We observed a unique lipid profile for each channel tested. NavMs and NavSp showed strong preference for different negatively-charged lipids (phosphatidylinositol and phosphatidylglycerol, respectively), whilst NaChBac exhibited a more modest variation with lipid type. To investigate the molecular bases of these differences we used synchrotron radiation circular dichroism spectroscopy to compare structures in liposomes of different composition, and molecular modeling and electrostatics calculations to rationalize the functional differences seen. We then examined pore-only constructs (with voltage sensor subdomains removed) and found that in these channels the lipid specificity was drastically reduced, suggesting that the specific lipid influences on voltage-gated sodium channels arise primarily from their abilities to interact with the voltage-sensing subdomains