Tuning ultrafast electron thermalization pathways in a van der Waals heterostructure

Ultrafast electron thermalization - the process leading to Auger recombination, carrier multiplication via impact ionization and hot carrier luminescence - occurs when optically excited electrons in a material undergo rapid electron-electron scattering to redistribute excess energy and reach electronic thermal equilibrium. Due to extremely short time and length scales, the measurement and manipulation of electron thermalization in nanoscale devices remains challenging even with the most advanced ultrafast laser techniques. Here, we overcome this challenge by leveraging the atomic thinness of two-dimensional van der Waals (vdW) materials in order to introduce a highly tunable electron transfer pathway that directly competes with electron thermalization. We realize this scheme in a graphene-boron nitride-graphene (G-BN-G) vdW heterostructure, through which optically excited carriers are transported from one graphene layer to the other. By applying an interlayer bias voltage or varying the excitation photon energy, interlayer carrier transport can be controlled to occur faster or slower than the intralayer scattering events, thus effectively tuning the electron thermalization pathways in graphene. Our findings, which demonstrate a novel means to probe and directly modulate electron energy transport in nanoscale materials, represent an important step toward designing and implementing novel optoelectronic and energy-harvesting devices with tailored microscopic properties.Comment: Accepted to Nature Physic

Generation of photovoltage in graphene on a femtosecond time scale through efficient carrier heating

Graphene is a promising material for ultrafast and broadband photodetection. Earlier studies addressed the general operation of graphene-based photo-thermoelectric devices, and the switching speed, which is limited by the charge carrier cooling time, on the order of picoseconds. However, the generation of the photovoltage could occur at a much faster time scale, as it is associated with the carrier heating time. Here, we measure the photovoltage generation time and find it to be faster than 50 femtoseconds. As a proof-of-principle application of this ultrafast photodetector, we use graphene to directly measure, electrically, the pulse duration of a sub-50 femtosecond laser pulse. The observation that carrier heating is ultrafast suggests that energy from absorbed photons can be efficiently transferred to carrier heat. To study this, we examine the spectral response and find a constant spectral responsivity between 500 and 1500 nm. This is consistent with efficient electron heating. These results are promising for ultrafast femtosecond and broadband photodetector applications.Comment: 6 pages, 4 figure

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

BACKGROUND: The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. Methods: FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. High rates of FBP1 and FBP3 expression were observed in all cancer types. RESULTS: There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p<0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p<0.001 and 0.05 resp.), but not in bladder or prostate cancer. CONCLUSIONS: The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors

Revisiting the Local Structure in Ge-Sb-Te based Chalcogenide Superlattices.

The technological success of phase-change materials in the field of data storage and functional systems stems from their distinctive electronic and structural peculiarities on the nanoscale. Recently, superlattice structures have been demonstrated to dramatically improve the optical and electrical performances of these chalcogenide based phase-change materials. In this perspective, unravelling the atomistic structure that originates the improvements in switching time and switching energy is paramount in order to design nanoscale structures with even enhanced functional properties. This study reveals a high- resolution atomistic insight of the [GeTe/Sb2Te3] interfacial structure by means of Extended X-Ray Absorption Fine Structure spectroscopy and Transmission Electron Microscopy. Based on our results we propose a consistent novel structure for this kind of chalcogenide superlattices

Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a reduction in muscle quality. However, there is inadequate empirical evidence to determine whether changes in muscle quality following exercise are associated with improvement in cardiorespiratory fitness (CRF) in individuals with T2DM. The objective of this study was to investigate the association between change in muscle quality following a 9-month intervention of aerobic training (AT), resistance training (RT) or a combination of both (ATRT) and cardiorespiratory fitness (CRF) in individuals with T2DM. Material and Methods A total of 196 participants were randomly assigned to a control, AT, RT, or combined ATRT for a 9-months intervention. The exposure variable was change in muscle quality [(Post: leg muscle strength/leg muscle mass)-[(Pre: leg muscle strength/leg muscle mass)]. Dependent variables were change in CRF measures including absolute and relative VO2peak, and treadmill time to exhaustion (TTE) and estimated metabolic equivalent task (METs). Results Continuous change in muscle quality was independently associated with change in absolute (β = 0.015; p = 0.019) and relative (β = 0.200; p = 0.005) VO2peak, and TTE (β = 0.170; p = 0.043), but not with estimated METs (p > 0.05). A significant trend was observed across tertiles of change in muscle quality for changes in absolute (β = 0.050; p = 0.005) and relative (β = 0.624; p = 0.002) VO2peak following 9 months of exercise training. No such association was observed for change in TTE and estimated METs (p > 0.05). Discussion: The results from this ancillary study suggest that change in muscle quality following exercise training is associated with a greater improvement in CRF in individuals with T2DM. Given the effect RT has on increasing muscle quality, especially as part of a recommended training program (ATRT), individuals with T2DM should incorporate RT into their AT regimens to optimize CRF improvement

Effect of novel technology-enabled multidimensional physical activity feedback in primary care patients at risk of chronic disease – the MIPACT study: A randomised controlled trial

© 2020 The Author(s). Background: Technological progress has enabled the provision of personalised feedback across multiple dimensions of physical activity that are important for health. Whether this multidimensional approach supports physical activity behaviour change has not yet been examined. Our objective was to examine the effectiveness of a novel digital system and app that provided multidimensional physical activity feedback combined with health trainer support in primary care patients identified as at risk of chronic disease. Methods: MIPACT was a parallel-group, randomised controlled trial that recruited patients at medium (≥10 and minimum clinically important difference, MCID). However, there was profound physical activity multidimensionality, and only a small proportion (5%) of patients had consistently low physical activity across all dimensions. Conclusion: In patients at risk of cardiovascular disease and/or type II diabetes, MIPACT did not increase mean physical activity. Using a sophisticated multidimensional digital approach revealed enormous heterogeneity in baseline physical activity in primary care patients, and practitioners may need to screen for low physical activity across dimensions rather than rely on disease-risk algorithms that are heavily influenced by age. Trial registration: This trial is registered with the ISRCTN registry (ISRCTN18008011; registration date 31 July 2013)

Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes