Proteins from morphologically differentiated neuroblastoma cells promote tubulin polymerization

Clonal cells (N18) of the mouse neuroblastoma C-1300 can be induced to undergo a morphological differentiation characterized by the outgrowth of very long neurites (> 150 microns) that contain many microtubules. Because the marked increase in the number and length of microtubules is apparently not due to an increase in the concentration of tubulin subunits, the possible role of additional macromolecules in the regulation of tubulin polymerization during neurite formation by N18 cells was examined. Using an in vitro system where the polymerization of low concentrations (< 4 mg/ml) of purified brain tubulin requires microtubule-associated proteins (MAPs), high-speed supernates (250,000 g) from neuroblastoma and glioma cells were assayed for their ability to replace MAPs in the polymerization of brain tubulin. Only the supernates from "differentiated" N18 cells were polymerization competent. Electron microscope observations of these supernates failed to demonstrate the presence of nucleation structures (rings or disks). The active factor(s) sedimented at approximately 7S on sucrose gradient centrifugation and eluted from 4B Sepharose in the region of 170,000 mol wt proteins. Furthermore, the inactive supernates from other cells did not inhibit polymerization when tested in the presence of limiting MAPs. Thus, microtubule formation accompanying neurite outgrowth in neuroblastoma cells appears to be regulated by the presence of additional macromolecular factor(s) that may be functionally equivalent to the MAPs found with brain microtubules

Co-Package Technology Platform for Low-Power and Low-Cost Data Centers

We report recent advances in photonic–electronic integration developed in the European research project L3MATRIX. The aim of the project was to demonstrate the basic building blocks of a co-packaged optical system. Two-dimensional silicon photonics arrays with 64 modulators were fabricated. Novel modulation schemes based on slow light modulation were developed to assist in achieving an efficient performance of the module. Integration of DFB laser sources within each cell in the matrix was demonstrated as well using wafer bonding between the InP and SOI wafers. Improved semiconductor quantum dot MBE growth, characterization and gain stack designs were developed. Packaging of these 2D photonic arrays in a chiplet configuration was demonstrated using a vertical integration approach in which the optical interconnect matrix was flip-chip assembled on top of a CMOS mimic chip with 2D vertical fiber coupling. The optical chiplet was further assembled on a substrate to facilitate integration with the multi-chip module of the co-packaged system with a switch surrounded by several such optical chiplets. We summarize the features of the L3MATRIX co-package technology platform and its holistic toolbox of technologies to address the next generation of computing challenges

Devolving the heartland: making up a new social policy for the 'South East'

Devolution appears to challenge the traditional regional and national hierarchies of the UK, but in practice the dominance of the South East of England has been maintained through active state intervention. As social welfare has increasingly been redefined through economic success and access to the labour market, the focus of social policy has shifted accordingly. In this context the South East has been re-imagined not as a symbol of inequality and a potential source of redistribution, but rather as driver of economic prosperity and 'national' (UK) well-being

Tunable and reconfigurable multi-tap microwave photonic filter based on dynamic Brillouin gratings in fibers

This paper was published in OPTICS EXPRESS 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://dx.doi.org/10.1364/OE.20.006157. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under lawWe propose and experimentally demonstrate new architectures to realize multi-tap microwave photonic filters, based on the generation of a single or multiple dynamic Brillouin gratings in polarization maintaining fibers. The spectral range and selectivity of the proposed periodic filters is extensively tunable, simply by reconfiguring the positions and the number of dynamic gratings along the fiber respectively. In this paper, we present a complete analysis of three different configurations comprising a microwave photonic filter implementation: a simple notch-type Mach-Zehnder approach with a single movable dynamic grating, a multi-tap performance based on multiple dynamic gratings and finally a stationary grating configuration based on the phase modulation of two counter-propagating optical waves by a common pseudo-random bit sequence (PRBS).The authors wish to acknowledge the financial support of the European Community's Seventh Framework Programme (FP 7) project GOSPEL; the GVA PROMETEO 2008/092, Infraestructura FEDER UPVOV08-3E-008, the Plan Nacional I + D TEC2011-29120-C05-05, the Swiss National Science Foundation through project 200021-134546 and the EPFL Space Center, the Israeli Science Foundation (ISF), and the KAMIN program of the Chief Scientist Office, Israel Ministry of Industry, Trade and Labor.Sancho Durá, J.; Sales Maicas, S.; Primerov, N.; Chin, S.; Antman, Y.; Zadok, A.; Thevenaz, L. (2012). Tunable and reconfigurable multi-tap microwave photonic filter based on dynamic Brillouin gratings in fibers. Optics Express. 20(6):6157-6162. https://doi.org/10.1364/OE.20.006157S61576162206Seeds, A. J. (2002). Microwave photonics. IEEE Transactions on Microwave Theory and Techniques, 50(3), 877-887. doi:10.1109/22.989971Capmany, J., & Novak, D. (2007). Microwave photonics combines two worlds. Nature Photonics, 1(6), 319-330. doi:10.1038/nphoton.2007.89Capmany, J., Ortega, B., Pastor, D., & Sales, S. (2005). Discrete-time optical Processing of microwave signals. Journal of Lightwave Technology, 23(2), 702-723. doi:10.1109/jlt.2004.838819Yao, J. (2009). Microwave Photonics. Journal of Lightwave Technology, 27(3), 314-335. doi:10.1109/jlt.2008.2009551Minasian, R. A. (2006). Photonic signal processing of microwave signals. IEEE Transactions on Microwave Theory and Techniques, 54(2), 832-846. doi:10.1109/tmtt.2005.863060Mørk, J., Kjær, R., van der Poel, M., & Yvind, K. (2005). Slow light in a semiconductor waveguide at gigahertz frequencies. Optics Express, 13(20), 8136. doi:10.1364/opex.13.008136Su, H., Kondratko, P., & Chuang, S. L. (2006). Variable optical delay using population oscillation and four-wave-mixing in semiconductor optical amplifiers. Optics Express, 14(11), 4800. doi:10.1364/oe.14.004800Song, K. Y., Herr�ez, M. G., & Th�venaz, L. (2005). Observation of pulse delaying and advancement in optical fibers using stimulated Brillouin scattering. Optics Express, 13(1), 82. doi:10.1364/opex.13.000082Song, K. Y., Zou, W., He, Z., & Hotate, K. (2008). All-optical dynamic grating generation based on Brillouin scattering in polarization-maintaining fiber. Optics Letters, 33(9), 926. doi:10.1364/ol.33.000926Song, K. Y., & Yoon, H. J. (2010). Observation of narrowband intrinsic spectra of Brillouin dynamic gratings. Optics Letters, 35(17), 2958. doi:10.1364/ol.35.002958Kwang Yong Song, Sanghoon Chin, Primerov, N., & Thevenaz, L. (2010). Time-Domain Distributed Fiber Sensor With 1 cm Spatial Resolution Based on Brillouin Dynamic Grating. Journal of Lightwave Technology, 28(14), 2062-2067. doi:10.1109/jlt.2010.205076

An Outcome-based Approach for the Creation of Fetal Growth Standards: Do Singletons and Twins Need Separate Standards?

Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks’ gestation in the United States (1995–2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999–2002 vs. 1995–1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards

Electrically pumped continuous-wave III–V quantum dot lasers on silicon

Reliable, efficient electrically pumped silicon-based lasers would enable full integration of photonic and electronic circuits, but have previously only been realized by wafer bonding. Here, we demonstrate continuous-wave InAs/GaAs quantum dot lasers directly grown on silicon substrates with a low threshold current density of 62.5 A cm–2, a room-temperature output power exceeding 105 mW and operation up to 120 °C. Over 3,100 h of continuous-wave operating data have been collected, giving an extrapolated mean time to failure of over 100,158 h. The realization of high-performance quantum dot lasers on silicon is due to the achievement of a low density of threading dislocations on the order of 105 cm−2 in the III–V epilayers by combining a nucleation layer and dislocation filter layers with in situ thermal annealing. These results are a major advance towards reliable and cost-effective silicon-based photonic–electronic integration

Alopecia in a Viable Phospholipase C Delta 1 and Phospholipase C Delta 3 Double Mutant

BACKGROUND: Inositol 1,4,5trisphosphate (IP(3)) and diacylglycerol (DAG) are important intracellular signalling molecules in various tissues. They are generated by the phospholipase C family of enzymes, of which phospholipase C delta (PLCD) forms one class. Studies with functional inactivation of Plcd isozyme encoding genes in mice have revealed that loss of both Plcd1 and Plcd3 causes early embryonic death. Inactivation of Plcd1 alone causes loss of hair (alopecia), whereas inactivation of Plcd3 alone has no apparent phenotypic effect. To investigate a possible synergy of Plcd1 and Plcd3 in postnatal mice, novel mutations of these genes compatible with life after birth need to be found. METHODOLOGY/PRINCIPAL FINDINGS: We characterise a novel mouse mutant with a spontaneously arisen mutation in Plcd3 (Plcd3(mNab)) that resulted from the insertion of an intracisternal A particle (IAP) into intron 2 of the Plcd3 gene. This mutation leads to the predominant expression of a truncated PLCD3 protein lacking the N-terminal PH domain. C3H mice that carry one or two mutant Plcd3(mNab) alleles are phenotypically normal. However, the presence of one Plcd3(mNab) allele exacerbates the alopecia caused by the loss of functional Plcd1 in Del(9)olt1Pas mutant mice with respect to the number of hair follicles affected and the body region involved. Mice double homozygous for both the Del(9)olt1Pas and the Plcd3(mNab) mutations survive for several weeks and exhibit total alopecia associated with fragile hair shafts showing altered expression of some structural genes and shortened phases of proliferation in hair follicle matrix cells. CONCLUSIONS/SIGNIFICANCE: The Plcd3(mNab) mutation is a novel hypomorphic mutation of Plcd3. Our investigations suggest that Plcd1 and Plcd3 have synergistic effects on the murine hair follicle in specific regions of the body surface

Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity

Increased susceptibility to infections, particularly respiratory viral infections, is a hallmark of advancing age. The underlying mechanisms are not well understood, and there is a scarcity of information regarding the contribution of the innate immune system, which is the first line of defense against infections. In the present study, we have investigated the effect of advancing age on plasmacytoid dendritic cell (PDC) function because they are critical in generating a robust antiviral response via the secretion of interferons (IFN). Our results indicate that PDCs from the aged are impaired in their capacity to secrete IFN-I in response to influenza virus and CPG stimulation. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated impaired phosphorylation of transcription factor, IRF-7. Furthermore, aged PDCs were observed to be impaired in their capacity to induce perforin and granzyme in CD8 T cells. Comparison of the antigen-presenting capacity of aged PDC with young PDC revealed that PDCs from aged subjects display reduced capacity to induce proliferation and IFN-gamma secretion in CD4 and CD8 T cells as compared with PDCs from young subjects. In summary, our study demonstrates that advancing age has a profound effect on PDC function at multiple levels and may therefore, be responsible for the increased susceptibility to infections in the elderly

The Effect of Consumers and Mutualists of Vaccinium membranaceum at Mount St. Helens: Dependence on Successional Context

In contrast to secondary succession, studies of terrestrial primary succession largely ignore the role of biotic interactions, other than plant facilitation and competition, despite the expectation that simplified interaction webs and propagule-dependent demographics may amplify the effects of consumers and mutualists. We investigated whether successional context determined the impact of consumers and mutualists by quantifying their effects on reproduction by the shrub Vaccinium membranaceum in primary and secondary successional sites at Mount St. Helens (Washington, USA), and used simulations to explore the effects of these interactions on colonization. Species interactions differed substantially between sites, and the combined effect of consumers and mutualists was much more strongly negative for primary successional plants. Because greater local control of propagule pressure is expected to increase successional rates, we evaluated the role of dispersal in the context of these interactions. Our simulations showed that even a small local seed source greatly increases population growth rates, thereby balancing strong consumer pressure. The prevalence of strong negative interactions in the primary successional site is a reminder that successional communities will not exhibit the distribution of interaction strengths characteristic of stable communities, and suggests the potential utility of modeling succession as the consequence of interaction strengths