Coupled charge and spin dynamics in high-density ensembles of nitrogen-vacancy centers in diamond

We studied the spin depolarization of ensembles of nitrogen-vacancy (NV) centers in nitrogen-rich single crystal diamonds. We found a strong dependence of the evolution of the polarized state in the dark on the concentration of NV centers. At low excitation power, we observed a simple exponential decay profile in the low-density regime and a paradoxical inverted exponential profile in the high-density regime. At higher excitation power, we observed complex behavior, with an initial sharp rise in luminescence signal after the preparation pulse followed by a slower exponential decay. Magnetic field and excitation laser power-dependent measurements suggest that the rapid initial increase of the luminescence signal is related to recharging of the nitrogen-vacancy centers (from neutral to negatively charged) in the dark. The slow relaxing component corresponds to the longitudinal spin relaxation of the NV ensemble. The shape of the decay profile reflects the interplay between two mechanisms: the NV charge state conversion in the dark and the longitudinal spin relaxation. These mechanisms, in turn, are influenced by ionization, recharging and polarization dynamics during excitation. Interestingly, we found that charge dynamics are dominant in NV-dense samples even at very feeble excitation power. These observations may be important for the use of ensembles of NV centers in precession magnetometry and sensing applications.Comment: 7 pages, 6 figure

On the thermodynamic path enabling a room-temperature, laser-assisted graphite to nanodiamond transformation

Nanodiamonds are the subject of active research for their potential applications in nano-magnetometry, quantum optics, bioimaging and water cleaning processes. Here, we present a novel thermodynamic model that describes a graphite-liquid-diamond route for the synthesis of nanodiamonds. Its robustness is proved via the production of nanodiamonds powders at room-temperature and standard atmospheric pressure by pulsed laser ablation of pyrolytic graphite in water. The aqueous environment provides a confinement mechanism that promotes diamond nucleation and growth, and a biologically compatible medium for suspension of nanodiamonds. Moreover, we introduce a facile physico-chemical method that does not require harsh chemical or temperature conditions to remove the graphitic byproducts of the laser ablation process. A full characterization of the nanodiamonds by electron and Raman spectroscopies is reported. Our model is also corroborated by comparison with experimental data from the literature

Reconstruction of a Segment of the UNESCO World Heritage Hadrian’s Villa Tunnel Network by Integrated GPR, Magnetic–Paleomagnetic, and Electric Resistivity Prospections

The authors are grateful to the Director of the Villa Adriana and Villa d’Este, Andrea Bruciati, for kindly allowing us to survey the archaeological area and to Benedetta Adembri for facilitating the research on site. We are also grateful to Francesco Ferruti and the students that helped us in the data acquisition. Finally, we thank Alessandro Bertani for his help in the acquisition and formal analysis of aerial photogrammetry data. This paper also benefited from four accurate reviews that allowed us to improve the manuscript.The following are available online at https://zenodo.org/record/3351757#.XVIUHdIRWUl, Figure S1: Local reference frames used for the acquisition of GPR data, Figure S2: UAV orthophoto of the study area (Plutonium−Inferi complex) with indication of the excavated areas, Tables S1–S13: Relevant migrated and unmigrated GPR profiles for areas 1 through 13, Table S10A, transversal migrated and unmigrated GPR profiles for Areas 10.Hadrian’s Villa is an ancient Roman archaeological site built over an ignimbritic tuff and characterized by abundant iron oxides, strong remnant magnetization, and elevated magnetic susceptibility. These properties account for the high-amplitude magnetic anomalies observed in this site and were used as a primary tool to detect deep archaeological features consisting of air-filled and soil-filled cavities of the tuff. An integrated magnetic, paleomagnetic, radar, and electric resistivity survey was performed in the Plutonium-Inferi sector of Hadrian’s Villa to outline a segment of the underground system of tunnels that link different zones of the villa. A preliminary paleomagnetic analysis of the bedrock unit and a high-resolution topographic survey by aerial photogrammetry allowed us to perform a computer-assisted modelling of the observed magnetic anomalies, with respect to the archaeological sources. The intrinsic ambiguity of this procedure was reduced through the analysis of ground penetrating radar and electric resistivity profiles, while a comprehensive picture of the buried archaeological features was built by integration of the magnetization model with radar amplitude maps. The final subsurface model of the Plutonium-Inferi complex shows that the observed anomalies are mostly due to the presence of tunnels, skylights, and a system of ditches excavated in the tuff.This research was funded by the Università degli Studi di Camerino, grants FAR Schettino 2016–2018 and FAR Pierantoni 2016–2018, and by the University of Oxford, Eugene Ludwig Fund, New College

Ultrahard carbon film from epitaxial two-layer graphene

Atomically thin graphene exhibits fascinating mechanical properties, although its hardness and transverse stiffness are inferior to those of diamond. To date, there hasn't been any practical demonstration of the transformation of multi-layer graphene into diamond-like ultra-hard structures. Here we show that at room temperature and after nano-indentation, two-layer graphene on SiC(0001) exhibits a transverse stiffness and hardness comparable to diamond, resisting to perforation with a diamond indenter, and showing a reversible drop in electrical conductivity upon indentation. Density functional theory calculations suggest that upon compression, the two-layer graphene film transforms into a diamond-like film, producing both elastic deformations and sp2-to-sp3 chemical changes. Experiments and calculations show that this reversible phase change is not observed for a single buffer layer on SiC or graphene films thicker than 3 to 5 layers. Indeed, calculations show that whereas in two-layer graphene layer-stacking configuration controls the conformation of the diamond-like film, in a multilayer film it hinders the phase transformation.Comment: Published online on Nature Nanotechnology on December 18, 201

Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities.

The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations. We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type) > 1) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression.We thank T. Jacks (Kras^LSL-G12D), A. Berns (p53^Fx) and the NIH Mouse repository for mice. We also thank Sam Kleeman and Patricia Ogger for assistance with redox cell profiling and cell viability assays, respectively. We are very thankful to CRUK CI BRU staff for support with in vivo work and all the members of the Martins lab for critical comments and advice. This work was supported by the Medical Research Council.This is the author accepted manuscript. The final version is available at http://www.nature.com/nature/journal/v531/n7592/full/nature16967.html

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells

Background:In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species.Method:The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout.Results:Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis.Conclusions:This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response

Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

PURPOSE ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data have suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. EXPERIMENTAL DESIGN We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin, and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient-derived xenografts (PDX). RESULTS Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX, lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth. CONCLUSIONS In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma