Fast and Uniform Optically-Switched Data Centre Networks Enabled by Amplitude Caching

We propose amplitude caching to optically equalise burst mode traffic without delay stages. Through a fast, optically-switched system prototype, we demonstrate burst-mode penalties can be mitigated to within 0.4 dB at the KR4 HD-FEC level

The operational window of carbon nanotube electrical wires treated with strong acids and oxidants

Conventional metal wires suffer from a significant degradation or complete failure in their electrical performance, when subjected to harsh oxidizing environments, however wires constructed from Carbon Nanotubes (CNTs) have been found to actually improve in their electrical performance when subjected to these environments. These opposing reactions may provide new and interesting applications for CNT wires. Yet, before attempting to move to any real-world harsh environment applications, for the CNT wires, it is essential that this area of their operation be thoroughly examined. To investigate this, CNT wires were treated with multiple combinations of the strongest acids and halogens. The wires were then subjected to conductivity measurements, current carrying capacity tests, as well as Raman, microscopy and thermogravimetric analysis to enable the identification of both the limits of oxidative conductivity boosting and the onset of physical damage to the wires. These experiments have led to two main conclusions. Firstly, that CNT wires may operate effectively in harsh oxidizing environments where metal wires would easily fail and secondly, that the highest conductivity increase of the CNT wires can be achieved through a process of annealing, acetone and HCl purification followed by either H2O2 and HClO4 or Br2 treatment

Characterization of cytochrome P450 CYP109E1 from Bacillus megaterium as a novel vitamin D3 hydroxylase

In this study the ability of CYP109E1 from Bacillus megaterium to metabolize vitamin D3 (VD3) was investigated. In an in vitro system using bovine adrenodoxin reductase (AdR) and adrenodoxin (Adx4-108), VD3 was converted by CYP109E1 into several products. Furthermore, a whole-cell system in B. megaterium MS941 was established. The new system showed a conversion of 95% after 24h. By NMR analysis it was found that CYP109E1 catalyzes hydroxylation of VD3 at carbons C-24 and C-25, resulting in the formation of 24(S)-hydroxyvitamin D3 (24S(OH)VD3), 25-hydroxyvitamin D3 (25(OH)VD3) and 24S,25-dihydroxyvitamin D3 (24S,25(OH)2VD3). Through time dependent whole-cell conversion of VD3, we identified that the formation of 24S,25(OH)2VD3 by CYP109E1 is derived from VD3 via the intermediate 24S(OH)VD3. Moreover, using docking analysis and site-directed mutagenesis, we identified important active site residues capable of determining substrate specificity and regio-selectivity. HPLC analysis of the whole-cell conversion with the I85A-mutant revealed an increased selectivity towards 25-hydroxylation of VD3 compared with the wild type activity, resulting in an approximately 2-fold increase of 25(OH)VD3 production (45mgl(-1)day(-1)) compared to wild type (24.5mgl(-1)day(-1))

Synchronous subnanosecond clock and data recovery for optically switched data centres using clock phase caching

The rapid growth in the amount of data being transferred within data centres, combined with the slowdown in Moore’s Law, creates challenges for the future scalability of electronically switched data-centre networks. Optical switches could offer a future-proof alternative, and photonic integration platforms have been demonstrated with nanosecond-scale optical switching times. End-to-end switching time is, however, currently limited by the clock and data recovery time, which typically takes microseconds, removing the benefits of nanosecond optical switching. Here we show that a clock phase caching technique can provide clock and data recovery times of under 625 ps (16 symbols at 25.6 Gb s−1). Our approach uses the measurement and storage of clock phase values in a synchronized network to simplify clock and data recovery versus conventional asynchronous approaches. We demonstrate the capabilities of our technique using a real-time prototype with commercial transceivers and validate its resilience against temperature variation and clock jitter

Technology and performances of silicon oxynitride waveguides for optomechanical sensors fabricated by plasma-enhanced chemical vapour deposition

The technology and performances of a micromachined channel waveguides, based on PECVD deposition of silicon oxynitride (SiOxNy) thin films, is presented. The deposition parameters of the PECVD process are studied in connection with their optical, mechanical and chemical properties. Waveguide deign is optimized allowing single mode, low loss propagation and high efficiency of coupling with single mode optical fiber. The proposed technology is applied to fabricate the pigtailed Mach-Zehnder interferometers, where the coupling from optical fiber to waveguide is based on the etch of U-grooves, supporting fibers in the same substrate as the waveguide substrate

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

Sub-Nanosecond Clock and Data Recovery in an Optically-Switched Data Centre Network

We demonstrate a clock and data recovery technique that achieves <625ps locking time for 25.6Gb/s-OOK and show its robustness under worst-case data centre temperature variation. The locking time was improved by 12×, making nanosecond optical switching viable in data centres

The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane

Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth

Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion

Endocrine therapies target the activation of the oestrogen receptor alpha (ERα) via distinct mechanisms, but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges via drug-specific epigenetic reprogramming. Resistant cells display a spectrum of phenotypical changes with invasive phenotypes evolving in lines resistant to the aromatase inhibitor (AI). Orthogonal genomics analysis of reprogrammed regulatory regions identifies individual drug-induced epigenetic states involving large topologically associating domains (TADs) and the activation of super-enhancers. AI-resistant cells activate endogenous cholesterol biosynthesis (CB) through stable epigenetic activation in vitro and in vivo. Mechanistically, CB sparks the constitutive activation of oestrogen receptors alpha (ERα) in AI-resistant cells, partly via the biosynthesis of 27-hydroxycholesterol. By targeting CB using statins, ERα binding is reduced and cell invasion is prevented. Epigenomic-led stratification can predict resistance to AI in a subset of ERα-positive patients

Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer

Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations. Understanding how these mutations impact on ER function is a prerequisite for identifying methods to treat breast cancer patients featuring such mutations. Towards this end, we used CRISPR-Cas9 genome editing to make a single allele knock-in of the most commonly mutated amino acid residue, tyrosine 537, in the estrogen-responsive MCF7 breast cancer cell line. Genomic analyses using RNA-seq and ER ChIP-seq demonstrated that the Y537S mutation promotes constitutive ER activity globally, resulting in estrogen-independent growth. MCF7-Y537S cells were resistant to the anti-estrogen tamoxifen and fulvestrant. Further, we show that the basal transcription factor TFIIH is constitutively recruited by ER-Y537S, resulting in ligand-independent phosphorylation of Serine 118 (Ser118) by the TFIIH kinase, cyclin-dependent kinase (CDK)7. The CDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growth of MCF7-Y537S cells. These studies confirm the functional importance of ER mutations in endocrine resistance, demonstrate the utility of knock-in mutational models for investigating alternative therapeutic approaches and highlight CDK7 inhibition as a potential therapy for endocrine-resistant breast cancer mediated by ER mutations