Far-field excitation of single graphene plasmon cavities with ultracompressed mode volumes

Acoustic graphene plasmons are highly confined electromagnetic modes carrying large momentum and low loss in the mid-infrared and terahertz spectra. However, until now they have been restricted to micrometer-scale areas, reducing their confinement potential by several orders of magnitude. Using a graphene-based magnetic resonator, we realized single, nanometer-scale acoustic graphene plasmon cavities, reaching mode volume confinement factors of ~5 × 1010 Such a cavity acts as a mid-infrared nanoantenna, which is efficiently excited from the far field and is electrically tunable over an extremely large broadband spectrum. Our approach provides a platform for studying ultrastrong-coupling phenomena, such as chemical manipulation via vibrational strong coupling, as well as a path to efficient detectors and sensors operating in this long-wavelength spectral range.I.E. would like to thank Eduardo J. C. Dias for fruitful discussions and Dr. Fabien Vialla. D.R.S acknowledges the support of AFOSR(FA9550-12-1-0491, FA9550-18-1-0187) grants. N.M.R.P. acknowledges support from the European Commission through the project “Graphene-Driven Revolutions in ICT and Beyond” (Ref. use CORE 3 reference, not CORE 2). N.M.R.P. and T.G.R. acknowledge COMPETE 2020, PORTUGAL 2020, FEDER and the Portuguese Foundation for Science and Technology (FCT) through project POCI-01- 0145-FEDER-028114. F.H.L.K. acknowledges financial support from the Government of Catalonia trough the SGR grant, and from the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R and D (SEV-2015- 0522), support by Fundacio Cellex Barcelona, Generalitat de Catalunya through the CERCA program, and the Mineco grants Ramón y Cajal (RYC-2012-12281, Plan Nacional (FIS2013-47161-P and FIS2014-59639-JIN) and the Agency for Management of University and Research Grants (AGAUR) 2017 SGR 1656. Furthermore, the research leading to these results has received funding from the European Union Seventh Framework Programme under grant agreements no.785219 and no. 881603 Graphene Flagship. This work was supported by the ERC TOPONANOP under grant agreement no. 726001 and the MINECO Plan Nacional Grant 2D-NANOTOP under reference no. FIS2016-81044-P

Near-unity light absorption in a monolayer WS2 van der Waals heterostructure cavity

Excitons in monolayer transition-metal-dichalcogenides (TMDs) dominate their optical response and exhibit strong light-matter interactions with lifetime-limited emission. While various approaches have been applied to enhance light-exciton interactions in TMDs, the achieved strength have been far below unity, and a complete picture of its underlying physical mechanisms and fundamental limits has not been provided. Here, we introduce a TMD-based van der Waals heterostructure cavity that provides near-unity excitonic absorption, and emission of excitonic complexes that are observed at ultralow excitation powers. Our results are in full agreement with a quantum theoretical framework introduced to describe the light-exciton-cavity interaction. We find that the subtle interplay between the radiative, nonradiative and dephasing decay rates plays a crucial role, and unveil a universal absorption law for excitons in 2D systems. This enhanced light-exciton interaction provides a platform for studying excitonic phase-transitions and quantum nonlinearities and enables new possibilities for 2D semiconductor-based optoelectronic devices.The authors thank Mr. David Alcaraz Iranzo, Dr. Fabien Vialla, and Dr. Antoine Reserbat-Plantey for fruitful discussions. F.H.L.K. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness through the "Severo Ochoa" Programme for Centres of Excellence in R and D (SEV-2015-0522), support by Fundacio Cellex Barcelona, Generalitat de Catalunya through the CERCA program, and the Mineco grants Ramon y Cajal (RYC-201212281, Plan Nacional (FIS2013-47161-P and FIS2014-59639JIN), and the Agency for Management of University and Research Grants (AGAUR) 2017 SGR 1656. Furthermore, the research leading to these results has received funding from the European Union Seventh Framework Programme under grant agreement numbers 785219 and 881603 Graphene Flagship. This work was supported by the ERC TOPONANOP under grant agreement number 726001 and the MINECO Plan Nacional Grant 2D-NANOTOP under reference number FIS2016-81044-P. S.T. acknowledges support from NSF DMR-1552220 and DMR-1838443. N.M.R.P acknowledges financing from European Commission through the project "Graphene-Driven Revolutions in ICT and Beyond" (ref. no. 785219) and from FEDER and the Portuguese Foundation for Science and Technology (FCT) through project POCI-010145-FEDER-028114. H.G. and B.F. acknowledge support from ERC advanced grant COMPLEXPLAS. J.H. and D.R. acknowledge the funding support by the NSF MRSEC program through Columbia in the Center for Precision Assembly of Superstratic and Superatomic Solids (DMR1420634)

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Analysis of Common and Specific Mechanisms of Liver Function Affected by Nitrotoluene Compounds

BACKGROUND: Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2ADNT) 4-amino-2,6-dinitrotoulene (4ADNT), 2,4-dinitrotoluene (2,4DNT) and 2,6-dinitrotoluene (2,6DNT)] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. CONCLUSIONS/SIGNIFICANCE: A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and physiological endpoints affected by these compounds

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo

Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p53. Mechanistically, this was linked to an upregulation of the E3 Ubiquitin ligase Mdm2, which targets p53 for degradation in c-Myc-deficient intestinal enterocytes. Further, low level overexpression of c-Myc, which does not impact on basal levels of apoptosis, elicited sustained apoptosis in response to DNA damage, suggesting c-Myc activity acts as a crucial cell survival rheostat following DNA damage. We also identify the importance of MYC during DNA damage-induced apoptosis in several other tissues, including the thymus and spleen, using systemic deletion of c-Myc throughout the adult mouse. Together, we have elucidated for the first time in vivo an essential role for endogenous c-Myc in signalling DNA damage-induced apoptosis through the control of the p53 tumour suppressor protein

An ErbB2/c-Src axis links bioenergetics with PRC2 translation to drive epigenetic 2 reprogramming and mammary tumourigenesis

Dysregulation of histone modifications promotes carcinogenesis by altering transcription. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the role of EZH2 in this setting is unclear due to the context-dependent functions of PRC2 and the heterogeneity of breast cancer. Moreover, the mechanisms underlying PRC2 overexpression in cancer are obscure. Here, using multiple models of breast cancer driven by the oncogene ErbB2, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 overexpression via control of mRNA translation. By stimulating mitochondrial ATP production, c-Src suppresses energy stress, permitting sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumourigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis