The Onset of Resolved Boundary-Layer Turbulence at Grey-Zone Resolutions

This is the final version. Available from Springer via the DOI in this record.Numerical weather prediction (NWP) models are now capable of operating at horizontal resolutions in the 100-m to 1-km range, a grid spacing similar in scale to that of the turbulent eddies present in the atmospheric convective boundary layer (CBL). Known as the ‘grey zone’ of turbulence, this regime is characterized by significant contributions from both the resolved and subgrid components to represent the dominant motions of the system. This study examines how the initiation of resolved turbulence – a concept commonly referred to as ‘spin-up’– can be delayed during the evolution of a simulated CBL in the grey zone. We identify the importance of imposed pseudo-random perturbations of potential temperature (θ) for the development of the resolved fields showing that without such perturbations, resolved turbulence does not become established at all. When the perturbations are organized, spin-up can develop more rapidly, and we find that the earliest spin-up times can be achieved by applying an idealized profile of variance to derive the θ perturbation values. The perturbation structures are shown to be most effective when applied at intervals following the mixed-layer time scale, t∗, rather than perturbing only at the initial time. We also propose a modification to the three-dimensional Smagorinsky turbulence closure, in which the Smagorinsky constant is replaced by a scale-dependent coefficient. Both the approaches of: (1) applying structured θ perturbations, and (2) using a dynamically-evolving Smagorinsky coefficient are shown to encourage faster spin-up independently of each other, but the best results clearly emerge when the two methods are applied concurrently

Grey zone simulations of the morning convective boundary layer development

Numerical simulations of two cases of morning boundary layer development are conducted to investigate the impact of grid resolution on mean profiles and turbulent kinetic energy (TKE) partitioning from the large eddy simulation (LES) to the mesoscale limit. Idealized LES, using the 3-D Smagorinsky scheme, is shown to be capable of reproducing the boundary layer evolution when compared against measurements. However, increasing grid spacing results in the damping of resolved TKE and the production of superadiabatic temperature profiles in the boundary layer. Turbulence initiation is significantly delayed, exhibiting an abrupt onset at intermediate resolutions. Two approaches, the bounding of vertical diffusion coefficient and the blending of the 3-D Smagorinsky with a nonlocal 1D scheme, are used to model subgrid diffusion at grey zone resolutions. Simulations are compared against the coarse-grained fields from the validated LES results for each case. Both methods exhibit particular strengths and weaknesses, indicating the compromise that needs to be made currently in high-resolution numerical weather prediction. The blending scheme is able to reproduce the adiabatic profiles although turbulence is underestimated in favor of the parametrized heat flux, and the spin-up of TKE remains delayed. In contrast, the bounding approach gives an evolution of TKE that follows the coarse-grained LES very well, relying on the resolved motions for the nonlocal heat flux. However, bounding gives unrealistic static instability in the early morning temperature profiles (similar to the 3-D Smagorinsky scheme) because model dynamics are unable to resolve TKE when the boundary layer is too shallow compared to the grid spacing.This work has been funded by the Natural Environment Research Council (NERC) GREYBLS (Modelling Grey Zone Boundary Layers) project (grant NE/K011456/1). We acknowledge the use of the MONSooN system, a collaborative facility supplied under the Joint Weather and Climate Research Programme, which is a strategic partnership between the Met Office and the Natural Environment Research Council

An unusual cause of haemoptysis in a young male

Inflammatory myofibroblastic tumours are reported to occur in a variety of sites, including the head and neck, abdominal organs, central nervous system and urinary tract. They only rarely occur in the lung. We report a case of a 25-year-old male admitted with haemoptysis. His chest radiograph showed a peripheral right lung opacity and computed tomography revealed a right lower lobe soft tissue density mass. Bronchoscopy and fine needle aspiration were unhelpful. a diagnosis of pulmonary carcinoma was made, and the patient underwent a right lower lobectomy. On pathology, the tumor was found to be an inflammatory pseudotumor. These lesion are extremely rare, constituting less than 1% of pulmonary malignancies, but are known to occur in young patients. We believe clinicians need to retain an index of suspicion for the presence of this disease in young patients, which can masquerade as more common malignancies

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Aspirin induces cell death and caspase-dependent phosphatidylserine externalization in HT-29 human colon adenocarcinoma cells

The induction of cell death by aspirin was analysed in HT-29 colon carcinoma cells. Aspirin induced two hallmarks of apoptosis: nuclear chromatin condensation and increase in phosphatidylserine externalization. However, aspirin did not induce either oligonucleosomal fragmentation of DNA, decrease in DNA content or nuclear fragmentation. The effect of aspirin on Annexin V binding was inhibited by the caspase inhibitor Z-VAD.fmk, indicating the involvement of caspases in the apoptotic action of aspirin. However, aspirin did not induce proteolysis of PARP, suggesting that aspirin does not increase nuclear caspase 3-like activity in HT-29 cells. This finding may be related with the ‘atypical’ features of aspirin-induced apoptosis in HT-29 cells. © 1999 Cancer Research Campaig

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1

Alzheimer's disease (AD) afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1) is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ) and abnormally phosphorylated tau (P-tau)), suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s) of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the “immediate early” viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted