Complete bandgaps in one-dimensional left-handed periodic structures

Artificially fabricated structures with periodically modulated parameters such as photonic crystals offer novel ways of controlling the flow of light due to the existence of a range of forbidden frequencies associated with a photonic bandgap. It is believed that modulation of the refractive index in all three spatial dimensions is required to open a complete bandgap and prevent the propagation of electromagnetic waves in all directions. Here we reveal that, in a sharp contrast to what was known before and contrary to the accepted physical intuition, a one-dimensional periodic structure containing the layers of transparent left-handed (or negative-index) metamaterial can trap light in three-dimensional space due to the existence of a complete bandgap.Comment: 4 pages, 5 figure

The continuing evolution of Energy Policy

As the world confronts the Covid-19 pandemic, we hope that all of you are doing well. We know that many lives have been greatly disrupted, and that world economic activity is slowing and maybe declining in some places. We have read reports that energy consumption has been greatly affected by the slowdown in world economic activity—likely contributing to the sharp plunge in oil prices earlier this year. We do not know how long this pandemic may last. As we look forward to the end of the pandemic and a recovering world economy, however, we wonder if and how energy systems may have to be transformed, and whether new energy policy needs and approaches will emerge. Will we see any change in the trajectory of adopting sustainable energy systems and reducing carbon emissions?In the academic world, many of us are now teleworking and teaching our courses online. This transition has proved time consuming—so we want to thank our many reviewers who are staying on or close to schedule. So far, Energy Policy has been mostly unaffected by the pandemic, but we must recognize that the Elsevier employees who are responsible for the operations side of the journal may at some time be affected by Covid-19.In the meantime, we want to keep you informed about some recent developments regarding Energy Policy, including a little about its history and our editorial priorities

Synthesis and dissociation of soliton molecules in parallel optical-soliton reactors

Mode-locked lasers have been widely used to explore interactions between optical solitons, including bound-soliton states that may be regarded as “photonic molecules”. Conventional mode-locked lasers normally, however, host at most only a few solitons, which means that stochastic behaviours involving large numbers of solitons cannot easily be studied under controlled experimental conditions. Here we report the use of an optoacoustically mode-locked fibre laser to create hundreds of temporal traps or “reactors” in parallel, within each of which multiple solitons can be isolated and controlled both globally and individually using all-optical methods. We achieve on-demand synthesis and dissociation of soliton molecules within these reactors, in this way unfolding a novel panorama of diverse dynamics in which the statistics of multi-soliton interactions can be studied. The results are of crucial importance in understanding dynamical soliton interactions and may motivate potential applications for all-optical control of ultrafast light fields in optical resonators

Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy</p> <p>Methods</p> <p>Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.</p> <p>Results</p> <p>HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.</p> <p>Conclusion</p> <p>Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.</p

ENSO feedbacks and their relationships with the mean state in a flux adjusted ensemble

The El Niño Southern Oscillation (ENSO) is governed by a combination of amplifying and damping ocean–atmosphere feedbacks in the equatorial Pacific. Here we quantify these feedbacks in a flux adjusted HadCM3 perturbed physics ensemble under present day conditions and a future emissions scenario using the Bjerknes Stability Index (BJ index). Relationships between feedbacks and both the present day biases and responses under climate change of the mean equatorial Pacific climate are investigated. Despite minimised mean sea surface temperature biases through flux adjustment, the important dominant ENSO feedbacks still show biases with respect to observed feedbacks and inter-ensemble diversity. The dominant positive thermocline and zonal advective feedbacks are found to be weaker in ensemble members with stronger mean zonal advection. This is due to a weaker sensitivity of the thermocline slope and zonal surface ocean currents in the east Pacific to surface wind stress anomalies. A drier west Pacific is also found to be linked to weakened shortwave and latent heat flux damping, suggesting a link between ENSO characteristics and the hydrological cycle. In contrast to previous studies using the BJ index that find positive relationships between the index and ENSO amplitude, here they are weakly or negatively correlated, both for present day conditions and for projected differences. This is caused by strong thermodynamic damping which dominates over positive feedbacks, which alone approximate ENSO amplitude well. While the BJ index proves useful for individual linear feedback analysis, we urge caution in using the total linear BJ index alone to assess the reasons for ENSO amplitude biases and its future change in models

Innovation and optimization in autoimmune encephalitis trials: the design and rationale for the Phase 3, randomized study of satralizumab in patients with NMDAR-IgG-antibody-positive or LGI1-IgG-antibody-positive autoimmune encephalitis (CIELO)

Background: Autoimmune encephalitis (AIE) encompasses a spectrum of rare autoimmune-mediated neurological disorders, which are characterized by brain inflammation and dysfunction. Autoantibodies targeting the N-methyl-d-aspartic acid receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) are the most common subtypes of antibody-positive AIE. Currently, there are no approved therapies for AIE. Interleukin-6 (IL-6) signaling plays a role in the pathophysiology of AIE. Satralizumab, a humanized, monoclonal recycling antibody that specifically targets the IL-6 receptor and inhibits IL-6 signaling, has demonstrated efficacy and safety in another autoantibody-mediated neuroinflammatory disease, aquaporin-4 immunoglobulin G antibody-positive neuromyelitis optica spectrum disorder, and has the potential to be an evidence-based disease modifying treatment in AIE. Objectives: CIELO will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of satralizumab compared with placebo in patients with NMDAR-immunoglobulin G antibody-positive (IgG+) or LGI1-IgG+ AIE. Study design: CIELO (NCT05503264) is a prospective, Phase 3, randomized, double-blind, multicenter, basket study that will enroll approximately 152 participants with NMDAR-IgG+ or LGI1-IgG+ AIE. Prior to enrollment, participants will have received acute first-line therapy. Part 1 of the study will consist of a 52-week primary treatment period, where participants will receive subcutaneous placebo or satralizumab at Weeks 0, 2, 4, and every 4 weeks thereafter. Participants may continue to receive background immunosuppressive therapy, symptomatic treatment, and rescue therapy throughout the study. Following Part 1, participants can enter an optional extension period (Part 2) to continue the randomized, double-blind study drug, start open-label satralizumab, or stop study treatment and continue with follow-up assessments. Endpoints: The primary efficacy endpoint is the proportion of participants with a ≥1-point improvement in the modified Rankin Scale (mRS) score from study baseline and no use of rescue therapy at Week 24. Secondary efficacy assessments include mRS, Clinical Assessment Scale of Autoimmune Encephalitis (CASE), time to rescue therapy, sustained seizure cessation and no rescue therapy, Montreal Cognitive Assessment, and Rey Auditory Verbal Learning Test (RAVLT) measures. Safety, pharmacokinetics, pharmacodynamics, exploratory efficacy, and biomarker endpoints will be captured. Conclusion: The innovative basket study design of CIELO offers the opportunity to yield prospective, robust evidence, which may contribute to the development of evidence-based treatment recommendations for satralizumab in AIE

HIV-1 Nef interaction influences the ATP-binding site of the Src-family kinase, Hck

Background: Nef is an HIV-1 accessory protein essential for viral replication and AIDS progression. Nef interacts with a multitude of host cell signaling partners, including members of the Src kinase family. Nef preferentially activates Hck, a Src-family kinase (SFK) strongly expressed in macrophages and other HIV target cells, by binding to its regulatory SH3 domain. Recently, we identified a series of kinase inhibitors that preferentially inhibit Hck in the presence of Nef. These compounds also block Nef-dependent HIV replication, validating the Nef-SFK signaling pathway as an antiretroviral drug target. Our findings also suggested that by binding to the Hck SH3 domain, Nef indirectly affects the conformation of the kinase active site to favor inhibitor association. Results: To test this hypothesis, we engineered a "gatekeeper" mutant of Hck with enhanced sensitivity to the pyrazolopyrimidine tyrosine kinase inhibitor, NaPP1. We also modified the RT loop of the Hck SH3 domain to enhance interaction of the kinase with Nef. This modification stabilized Nef:Hck interaction in solution-based kinase assays, as a way to mimic the more stable association that likely occurs at cellular membranes. Introduction of the modified RT loop rendered Hck remarkably more sensitive to activation by Nef, and led to a significant decrease in the K mssssfor ATP as well as enhanced inhibitor potency. Conclusions: These observations suggest that stable interaction with Nef may induce Src-family kinase active site conformations amenable to selective inhibitor targeting. © 2012 Pene-Dumitrescu et al; licensee BioMed Central Ltd

Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin