Computational analysis of energy and cost efficient retrofitting measures for the French house

Energy-efficient housing has become a mandatory aim to address climate change. This paper presents a computational analysis taking a French single family house as a case study, and aims to investigate both energy and cost-efficiency of market available retrofit measures using dynamic thermal modelling. A parametric analysis tool was developed to run automated batch-simulations using EnergyPlus simulation engine and to calculate the cost associated with retrofit measures, at each simulation run. The automated simulations are carried out, using an exhaustive search technique, for all permutations of measures. These included different building fabrics, ventilation strategies, levels of air-tightness and 5 different heating systems for 4 main climatic regions of France (7680 variants for each of the 4 climatic region). In this analysis, an optimization problem is set to minimise the delivered energy and retrofitting investment cost subject to an energy-saving minimum limit, payback criterion, and summer overheating-risk. The results showed optimum solutions with different fabric and system retrofit combinations that varied in numbers for the different climatic zones. The upper bound of optimum investment cost varied from 80 to 290 €/m2 for Nice and Paris, respectively

Jagged2 controls the generation of motor neuron and oligodendrocyte progenitors in the ventral spinal cord

In the developing spinal cord, motor neurons (MNs) and oligodendrocytes arise sequentially from a common pool of progenitors. However, the genetic network responsible for this neurogenesis to gliogenesis switch is largely unknown. A transcriptome analysis identified the Notch ligand Jagged2 (JAG2) as a Sonic hedgehog-regulated factor transiently expressed in MN progenitors (pMNs). In vivo loss- and gain-of-function experiments show that JAG2 schedules the differentiation of the pMN progenitors. At early developmental stages, Olig2 expressing pMN progenitors that enter the differentiation pathway exclusively generate MNs. At these times, the activation of the Notch pathway by JAG2 maintains selected pMN progenitors in an undifferentiated state by two mechanisms; first it inhibits MN generation by reducing Olig2 proteins levels, and second it directly inhibits the premature generation of oligodendrocyte progenitors (OLPs) by maintaining high levels of Hes5. Later, extinction of JAG2 from the pMN results in the loss of Hes5 expression, heralding the gliogenic phase of pMN progenitors. Strikingly, downregulation of JAG2 in pMN progenitors is sufficient to promote the precocious generation of OLPs. Together these data provide evidence that JAG2 is a key regulator of the timely and ordered generation of two of the defining cell types in the spinal cord, MNs and OLPs

Engineered arrays of NV color centers in diamond based on implantation of CN- molecules through nanoapertures

We report a versatile method to engineer arrays of nitrogen-vacancy (NV) color centers in dia- mond at the nanoscale. The defects were produced in parallel by ion implantation through 80 nm diameter apertures patterned using electron beam lithography in a PMMA layer deposited on a diamond surface. The implantation was performed with CN- molecules which increased the NV defect formation yield. This method could enable the realization of a solid-state coupled-spin array and could be used for positioning an optically active NV center on a photonic microstructure.Comment: 12 pages, 3 figure

Experimental loophole-free violation of a Bell inequality using entangled electron spins separated by 1.3 km

For more than 80 years, the counterintuitive predictions of quantum theory have stimulated debate about the nature of reality. In his seminal work, John Bell proved that no theory of nature that obeys locality and realism can reproduce all the predictions of quantum theory. Bell showed that in any local realist theory the correlations between distant measurements satisfy an inequality and, moreover, that this inequality can be violated according to quantum theory. This provided a recipe for experimental tests of the fundamental principles underlying the laws of nature. In the past decades, numerous ingenious Bell inequality tests have been reported. However, because of experimental limitations, all experiments to date required additional assumptions to obtain a contradiction with local realism, resulting in loopholes. Here we report on a Bell experiment that is free of any such additional assumption and thus directly tests the principles underlying Bell's inequality. We employ an event-ready scheme that enables the generation of high-fidelity entanglement between distant electron spins. Efficient spin readout avoids the fair sampling assumption (detection loophole), while the use of fast random basis selection and readout combined with a spatial separation of 1.3 km ensure the required locality conditions. We perform 245 trials testing the CHSH-Bell inequality $S \leq 2$ and find $S = 2.42 \pm 0.20$. A null hypothesis test yields a probability of $p = 0.039$ that a local-realist model for space-like separated sites produces data with a violation at least as large as observed, even when allowing for memory in the devices. This result rules out large classes of local realist theories, and paves the way for implementing device-independent quantum-secure communication and randomness certification.Comment: Raw data will be made available after publicatio

Quantitative nanoscale vortex-imaging using a cryogenic quantum magnetometer

Microscopic studies of superconductors and their vortices play a pivotal role in our understanding of the mechanisms underlying superconductivity. Local measurements of penetration depths or magnetic stray-fields enable access to fundamental aspects of superconductors such as nanoscale variations of superfluid densities or the symmetry of their order parameter. However, experimental tools, which offer quantitative, nanoscale magnetometry and operate over the large range of temperature and magnetic fields relevant to address many outstanding questions in superconductivity, are still missing. Here, we demonstrate quantitative, nanoscale magnetic imaging of Pearl vortices in the cuprate superconductor YBCO, using a scanning quantum sensor in form of a single Nitrogen-Vacancy (NV) electronic spin in diamond. The sensor-to-sample distance of ~10nm we achieve allows us to observe striking deviations from the prevalent monopole approximation in our vortex stray-field images, while we find excellent quantitative agreement with Pearl's analytic model. Our experiments yield a non-invasive and unambiguous determination of the system's local London penetration depth, and are readily extended to higher temperatures and magnetic fields. These results demonstrate the potential of quantitative quantum sensors in benchmarking microscopic models of complex electronic systems and open the door for further exploration of strongly correlated electron physics using scanning NV magnetometry.Comment: Main text (5 pages, 4 figures) plus supplementary material (5 pages, 6 figures). Comments welcome. Further information under http://www.quantum-sensing.c

Strong mechanical driving of a single electron spin

Quantum devices for sensing and computing applications require coherent quantum systems which can be manipulated in a fast and robust way. Such quantum control is typically achieved using external electric or magnetic fields which drive the system's orbital or spin degrees of freedom. However, most of these approaches require complex and unwieldy antenna or gate structures, and with few exceptions are limited to the regime of weak driving. Here, we present a novel approach to strongly and coherently drive a single electron spin in the solid state using internal strain fields in an integrated quantum device. Specifically, we study individual Nitrogen-Vacancy (NV) spins embedded in diamond mechanical oscillators and exploit the intrinsic strain coupling between spin and oscillator to strongly drive the spins. As hallmarks of the strong driving regime, we directly observe the energy spectrum of the emerging phonon-dressed states and employ our strong, continuous driving for enhancement of the NV spin coherence time. Our results constitute a first step towards strain-driven, integrated quantum devices and open new perspectives to investigate unexplored regimes of strongly driven multi-level systems and to study exotic spin dynamics in hybrid spin-oscillator devices.We gratefully acknowledge financial support from SNI; NCCR QSIT; SNF grants 200021_143697; and EU FP7 grant 611143 (DIADEMS). AN holds a University Research Fellowship from the Royal Society and acknowledges support from the Winton Programme for the Physics of Sustainability.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nphys341

Controllable effects of quantum fluctuations on spin free-induction decay at room temperature

Fluctuations of local fields cause decoherence of quantum objects. Usually at high temperatures, thermal noises are much stronger than quantum fluctuations unless the thermal effects are suppressed by certain techniques such as spin echo. Here we report the discovery of strong quantum-fluctuation effects of nuclear spin baths on free-induction decay of single electron spins in solids at room temperature. We find that the competition between the quantum and thermal fluctuations is controllable by an external magnetic field. These findings are based on Ramsey interference measurement of single nitrogen-vacancy center spins in diamond and numerical simulation of the decoherence, which are in excellent agreement

Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer

Introduction: Endothelin (EDN) signalling plays a crucial role in cell differentiation, proliferation and migration processes. There is compelling evidence that altered EDN signalling is involved in carcinogenesis by modulating cell survival and promoting invasiveness. To date, most reports have focused on the oncogenic potential of EDN1 and EDN2, both of which are overexpressed in various tumour entities. Here, we aimed at a first comprehensive analysis on EDN3 expression and its implication in human breast cancer. Methods: EDN3 mRNA expression was assessed by Northern blotting in normal human tissues (n = 9) as well as in matched pairs of normal and tumourous tissues from breast specimens (n = 50). EDN3 mRNA expression in breast cancer was further validated by real-time polymerase chain reaction (PCR) (n = 77). A tissue microarray was used to study EDN3 protein expression in breast carcinoma (n = 150) and normal breast epithelium (n = 44). EDN3 promoter methylation was analysed by methylation-specific PCR in breast cell lines (n = 6) before and after demethylating treatment, normal breast tissues (n = 17) and primary breast carcinomas (n = 128). EDN3 expression and methylation data were statistically correlated with clinical patient characteristics and patient outcome. Results: Loss of EDN3 mRNA expression in breast cancer, as initially detected by array-based expression profiling, could be confirmed by Northern blot analysis (> 2-fold loss in 96%) and real-time PCR (> 2-fold loss in 78%). Attenuated EDN3 expression in breast carcinoma was also evident at the protein level (45%) in association with adverse patient outcome in univariate (P = 0.022) and multivariate (hazard ratio 2.0; P = 0.025) analyses. Hypermethylation of the EDN3 promoter could be identified as the predominant mechanism leading to gene silencing. Reversion of the epigenetic lock by 5-aza-2'-deoxycytidine and trichostatin A resulted in EDN3 mRNA reexpression in vitro. Furthermore, EDN3 promoter hypermethylation was detected in 70% of primary breast carcinomas with significant association to loss of EDN3 mRNA expression (P = 0.005), whilst normal matched breast tissues revealed no EDN3 promoter methylation. Conclusions EDN3 is a frequent target of epigenetic inactivation in human breast cancer, potentially contributing to imbalanced EDN signalling commonly found in this disease. The clinical implication supports the view that EDN3, in contrast to EDN1 and EDN2, may act as natural tumour suppressor in the human mammary gland

Therapeutic targets for bone metastases in breast cancer

Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3, c-Src, cathepsin K), osteoblasts (dickkopf-1, activin A, endothelin A) and the bone marrow microenvironment (transforming growth factor β, bone morphogenetic proteins, chemokine CXCL-12 and its receptor CXCR4). The clinical exploitation of these bone-targeted agents will provide oncologists with novel therapeutic strategies for the treatment of skeletal lesions in breast cancer

Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta-gonad-mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso-ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs