Entanglement-enhanced probing of a delicate material system

Quantum metrology uses entanglement and other quantum effects to improve the sensitivity of demanding measurements. Probing of delicate systems demands high sensitivity from limited probe energy and has motivated the field's key benchmark-the standard quantum limit. Here we report the first entanglement-enhanced measurement of a delicate material system. We non-destructively probe an atomic spin ensemble by means of near-resonant Faraday rotation, a measurement that is limited by probe-induced scattering in quantum-memory and spin-squeezing applications. We use narrowband, atom-resonant NOON states to beat the standard quantum limit of sensitivity by more than five standard deviations, both on a per-photon and per-damage basis. This demonstrates quantum enhancement with fully realistic loss and noise, including variable-loss effects. The experiment opens the way to ultra-gentle probing of single atoms, single molecules, quantum gases and living cells.Comment: 7 pages, 8 figures; Nature Photonics, advance online publication, 16 December 201

A monolithic integrated photonic microwave filter

[EN] Meeting the increasing demand for capacity in wireless networks requires the harnessing of higher regions in the radiofrequency spectrum, reducing cell size, as well as more compact, agile and power-efficient base stations that are capable of smoothly interfacing the radio and fibre segments. Fully functional microwave photonic chips are promising candidates in attempts to meet these goals. In recent years, many integrated microwave photonic chips have been reported in different technologies. To the best of our knowledge, none has monolithically integrated all the main active and passive optoelectronic components. Here, we report the first demonstration of a tunable microwave photonics filter that is monolithically integrated into an indium phosphide chip. The reconfigurable radiofrequency photonic filter includes all the necessary elements (for example, lasers, modulators and photodetectors), and its response can be tuned by means of control electric currents. This is an important step in demonstrating the feasibility of integrated and programmable microwave photonic processors.The authors acknowledge financial support from the Spanish Centro para el Desarrollo Tecnologico Industrial (CDTI) through the NEOTEC start-up programme, the European Commission through the 7th Research Framework Programme project, Photonic Advanced Research and Development for Integrated Generic Manufacturing (FP7-PARADIGM), the Generalitat Valenciana through the Programa para grupos de Investigacion de Excelencia (PROMETEO) project code 2013/012, the Spanish Ministerio de Economia y Comercio (MINECO) via project TEC2013-42332-P, PIF4ESP, and the Unwersitat Politecnica de Valencia (UPVOV) through projects 10-3E-492 and 08-3E-008 funded by the Fondos Europeos de Desarrollo Regional (FEDER). J.S. Fandino acknowledges financial support from Formacion de Profesorado Universitario (FPU) grant AP2010-1595.Sanchez Fandiño, JA.; Muñoz Muñoz, P.; Doménech Gómez, JD.; Capmany Francoy, J. (2017). A monolithic integrated photonic microwave filter. Nature Photonics. 11(2):124-129. https://doi.org/10.1038/NPHOTON.2016.233S124129112Novak, D. et al. Radio-over-fiber technologies for emerging wireless systems. IEEE J. Quantum Electron. 52, 1–11 (2016).Waterhouse, R. & Novak, D. Realizing 5G: microwave photonics for 5G mobile wireless systems. IEEE Microw. Mag. 16, 84–92 (2015).Won, R. Microwave photonics shines. Nat. Photon. 5, 736 (2011).Capmany, J. & Novak, D. Microwave photonics combines two worlds. Nat. Photon. 1, 319–330 (2007).Yao, J. Microwave photonics. J. Lightw. Technol. 27, 314–335 (2009).Andrews, J. G. et al. What will 5G be? IEEE J. Sel. Areas Commun. 32, 1065–1082 (2014).Gosh, A., et al. 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Integrated InP–InGaAsP tuneable coupled ring optical bandpass filters with zero insertion loss. Opt. Express 19, 7816–7826 (2011).Fandiño, J. S. & Muñoz, P. Photonics-based microwave frequency measurement using a double-sideband suppressed-carrier modulation and an InP integrated ring-assisted Mach–Zehnder interferometer filter. Opt. Lett. 38, 4316–4319 (2013).Burla, M. et al. On-chip ultra-wideband microwave photonic phase shifter and true time delay line based on a single phase-shifted waveguide Bragg grating. In IEEE International Topical Meeting on Microwave Photonics 92–95 (IEEE, 2013).Shi, W., Veerasubramanian, V., Patel, D. & Plant, D. Tuneable nanophotonic delay lines using linearly chirped contradirectioinal couplers with uniform Bragg gratings. Opt. Lett. 39, 701–703 (2014).Guan, B. et al. CMOS compatible reconfigurable silicon photonic lattice filters using cascaded unit cells for RF-photonic processing. IEEE J. Sel. Top. Quantum Electron. 20, 359–368 (2014).Khan, M. H. et al. Ultrabroad-bandwidth arbitrary radiofrequency waveform generation with a silicon photonic chip-based spectral shaper. Nat. Photon. 4, 117–122 (2010).Pagani, M. et al. Instantaneous frequency measurement system using four-wave mixing in an ultra-compact long silicon waveguide. In Proc. 41st European Conf. on Optical Communication (ECOC) 1–3 (IEEE, 2015).Khilo, A. et al. Photonic ADC: overcoming the bottleneck of electronic jitter. Opt. Express 20, 4454–4469 (2012).Wang, J. et al. Reconfigurable radio-frequency arbitrary waveforms synthesized in a silicon photonic chip. Nat. Commun. 6, 5957 (2015).Marpaung, D. et al. Si3N4 ring resonator-based microwave photonic notch filter with an ultrahigh peak rejection. Opt. Express 21, 23286–23294 (2013).Zhuang, L. et al. Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links. Opt. Express 21, 25999–26013 (2013).Marpaung, D., Chevalier, L., Burla, M. & Roeloffzen, C. Impulse radio ultrawideband pulse shaper based on a programmable photonic chip frequency discriminator. Opt. Express 19, 24838–24848 (2011).Marpaung, D. On-chip photonic-assisted instantaneous microwave frequency measurement system. IEEE Photon. Technol. Lett. 25, 837–840 (2013).Burla, M. et al. On-chip CMOS compatible reconfigurable optical delay line with separate carrier tuning for microwave photonic signal processing. Opt. Express 19, 21475–21484 (2011).Tan, K. et al. Photonic-chip-based all-optical ultra-wideband pulse generation via XPM and birefringence in a chalcogenide waveguide. Opt. Express 21, 2003–2011 (2013).Pagani, M. et al. Tuneable wideband microwave photonic phase shifter using on-chip stimulated Brillouin scattering. Opt. Express 22, 28810–28818 (2014).Pérez, D., Gasulla, I. & Capmany, J. Software-defined reconfigurable microwave photonics processor. Opt. Express 23, 14640–14654 (2015).Capmany, J., Gasulla, I. & Pérez, D. Microwave photonics: the programmable processor. Nat. Photon. 10, 6–8 (2016).Zhuang, L., Roeloffzen, C. G. H., Hoekman, M., Boller, K.-J. & Lowery, A. J. Programmable photonic signal processor chip for radiofrequency applications. Optica 2, 854–859 (2015).Roeloffzen, C. G. et al. Silicon nitride microwave photonic circuits. Opt. Express 21, 22937–22961 (2013).Liu, W. et al. A fully reconfigurable photonic integrated signal processor. Nat. Photon. 10, 190–195 (2016).Madsen, C. K. & Zhao, J. H. Optical Filter Design and Analysis: A Signal Processing Approach (Wiley, 1999).Román, J., Frankel, M. Y. & Esman, R. D. Spectral characterization of fiber gratings with high resolution. Opt. Lett. 23, 939–941 (1998).Hernández, R., Loayssa, A. & Benito, D. Optical vector network analysis based on single-sideband modulation. Opt. Eng. 43, 2418–2421 (2004).Jinguji, K. & Oguma, M. Optical half-band filters. J. Lightw. Technol. 18, 252–259 (2000).Madsen, C. K. 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Effect of Hydrogen Peroxide on Immersion Challenge of Rainbow Trout Fry with Flavobacterium psychrophilum

An experimental model for immersion challenge of rainbow trout fry (Oncorhynchus mykiss) with Flavobacterium psychrophilum, the causative agent of rainbow trout fry syndrome and bacterial cold water disease was established in the present study. Although injection-based infection models are reliable and produce high levels of mortality attempts to establish a reproducible immersion model have been less successful. Various concentrations of hydrogen peroxide (H₂O₂) were evaluated before being used as a pre-treatment stressor prior to immersion exposure to F. psychrophilum. H₂O₂ accelerated the onset of mortality and increased mortality approximately two-fold; from 9.1% to 19.2% and from 14.7% to 30.3% in two separate experiments. Clinical signs observed in the infected fish corresponded to symptoms characteristically seen during natural outbreaks. These findings indicate that pre-treatment with H₂O₂ can increase the level of mortality in rainbow trout fry after exposure to F. psychrophilum

Antecedents and consequences of effectuation and causation in the international new venture creation process

The selection of the entry mode in an international market is of key importance for the venture. A process-based perspective on entry mode selection can add to the International Business and International Entrepreneurship literature. Framing the international market entry as an entrepreneurial process, this paper analyzes the antecedents and consequences of causation and effectuation in the entry mode selection. For the analysis, regression-based techniques were used on a sample of 65 gazelles. The results indicate that experienced entrepreneurs tend to apply effectuation rather than causation, while uncertainty does not have a systematic influence. Entrepreneurs using causation-based international new venture creation processes tend to engage in export-type entry modes, while effectuation-based international new venture creation processes do not predetermine the entry mod

TNFR1 inhibition with a nanobody protects against EAE development in mice

TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signals via TNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG(35-55)-induced EAE. Because TROS does not cross-react with mouse TNFR1, we generated mice expressing human TNFR1 in a mouse TNFR1-knockout background (hTNFR1 Tg), and we determined biodistribution of Tc-99m-TROS and effectiveness of TROS in EAE in those mice. Biodistribution analysis demonstrated that intraperitoneally injected TROS is retained more in organs of hTNFR1 Tg mice compared to wild type mice. TROS was also detected in the cerebrospinal fluid (CSF) of hTNFR1 Tg mice. Prophylactic TROS administration significantly delayed disease onset and ameliorated its symptoms. Moreover, treatment initiated early after disease onset prevented further disease development. TROS reduced spinal cord inflammation and neuroinflammation, and preserved myelin and neurons. Collectively, our data illustrate that TNFR1 is a promising therapeutic target in MS

Real-life use of vitamin D_3-fortified bread and milk during a winter season: the effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish families, the VitmaD study.

Common genetic variants rs10741657 and rs10766197 in CYP2R1 and rs4588 and rs842999 in GC and a combined genetic risk score (GRS) of these four variants influence late summer 25-hydroxyvitamin D (25(OH)D) concentrations. The objectives were to identify those who are most at risk of developing low vitamin D status during winter and to assess whether vitamin D(3)-fortified bread and milk will increase 25(OH)D concentrations in those with genetically determined low 25(OH)D concentrations at late summer. We used data from the VitmaD study. Participants were allocated to either vitamin D(3)-fortified bread and milk or non-fortified bread and milk during winter. In the fortification group, CYP2R1 (rs10741657) and GC (rs4588 and rs842999) were statistically significantly associated with winter 25(OH)D concentrations and CYP2R1 (rs10766197) was borderline significant. There was a negative linear trend between 25(OH)D concentrations and carriage of 0–8 risk alleles (p < 0.0001). No association was found for the control group (p = 0.1428). There was a significant positive linear relationship between different quintiles of total vitamin D intake and the increase in 25(OH)D concentrations among carriers of 0–2 (p = 0.0012), 3 (p = 0.0001), 4 (p = 0.0118) or 5 (p = 0.0029) risk alleles, but not among carriers of 6–8 risk alleles (p = 0.1051). Carriers of a high GRS were more prone to be vitamin D deficient compared to carriers of a low GRS. Furthermore, rs4588-AA carriers have a low but very stable 25(OH)D concentration, and interestingly, also low PTH level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12263-014-0413-7) contains supplementary material, which is available to authorized users

S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast

INTRODUCTION: The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1. METHODS: In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry. RESULTS: S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27(kip1 )(n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36). CONCLUSION: The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1

Differential regulation of specific genes in MCF-7 and the ICI 182780-resistant cell line MCF-7/182R-6

To elucidate the mechanisms involved in anti-oestrogen resistance, two human breast cancer cell lines MCF-7 and the ICI 182780-resistant cell line, MCF-7/182R-6, have been compared with regard to oestrogen receptor (ER) expression, ER function, ER regulation, growth requirements and differentially expressed gene products. MCF-7/182R-6 cells express a reduced level of ER protein. The ER protein is functional with respect to binding of oestradiol and the anti-oestrogens tamoxifen, 4-hydroxy-tamoxifen and ICI 182780, whereas expression and oestrogen induction of the progesterone receptor is lost in MCF-7/182R-6 cells. The ER protein and the ER mRNA are regulated similarly in the two cell lines when subjected to treatment with oestradiol or ICI 182780. Oestradiol down-regulates ER mRNA and ER protein expression. ICI 182780 has no initial effect on ER mRNA expression whereas the ER protein level decreases rapidly in cells treated with ICI 182780, indicating a severely decreased stability of the ER protein when bound to ICI 182780. In vitro growth experiments revealed that the ICI 182780-resistant cell line had evolved to an oestradiol-independent phenotype, able to grow with close to maximal growth rate both in the absence of oestradiol and in the presence of ICI 182780. Comparison of gene expression between the two cell lines revealed relatively few differences, indicating that a limited number of changes is involved in the development of anti-oestrogen resistance. Identification of the differentially expressed gene products are currently in progress. © 1999 Cancer Research Campaig