Thermal Casimir Force between Magnetic Materials

We investigate the Casimir pressure between two parallel plates made of magnetic materials at nonzero temperature. It is shown that for real magnetodielectric materials only the magnetic properties of ferromagnets can influence the Casimir pressure. This influence is accomplished through the contribution of the zero-frequency term of the Lifshitz formula. The possibility of the Casimir repulsion through the vacuum gap is analyzed depending on the model used for the description of the dielectric properties of the metal plates.Comment: 9 pages, 3 figures. Contribution to the Proceedings of QFEXT09, Norman, OK, September 21-25, 200

Non-human TRIM5 variants enhance recognition of HIV-1-infected cells by CD8+ T cells

Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type-1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two non-human TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the non-immunosuppressive analog of cyclosporin A, SmBz-CsA, we found a significant reduction in CD107a/MIP1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for non-human TRIM5 variants in cellular immunity. We hypothesise that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The non-human TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T-cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection

Doping effects in the coupled, two-leg spin ladder BiCu2PO6

We report preparation, x-ray diffraction, magnetic susceptibility chi(T) and heat capacity Cp(T) measurements on the undoped samples as also samples with Zn-doped (S = 0) at Cu site, Ni doped (S = 1) at Cu site, and Ca-doped (holes) at Bi site in the coupled two-leg spin ladder system BiCu2PO6. While, Zn shows complete solid solubility, Ni could be doped to about 20% and Ca to about 15%. Magnetization and heat capacity data in the undoped compound point towards the existence of frustration effects. In all the samples, the chi(T) at low temperature increases with doping content. The Zn-induced susceptibility is smaller than that due to effective S=1/2 moments possibly due to frustrating next-nearest-neighbor interactions along the leg. For Zn content x > 0.01, chi(T) deviates from the Curie-law at low temperatures. The magnetic specific heat data Cm(T) for the Zn-doped samples show weak anomalies at low temperature in agreement with chi(T) behavior. The anomalies are suggestive of spin freezing at low-T. In contrast, prominent effects are observed in chi(T) and Cm(T) on Ni-doped samples. The zero-field-cooled (ZFC) and field-cooled (FC) chi(T) data are different from each other at low temperature unlike that for Zn doped samples, clearly indicating a transition to a spin-glass like phase. No anomalies were found in Ca- or Pb-doped samples.Comment: 16 pages, 9 figures, Submitted to J. Phy. Cond. Matte

On the Spiral Structure of the Milky Way Galaxy

We consider the possible pattern of the overall spiral structure of the Galaxy, using data on the distribution of neutral (atomic), molecular, and ionized hydrogen, on the base of the hypothesis of the spiral structure being symmetric, i.e. the assumption that spiral arms are translated into each other for a rotation around the galactic center by 180{\deg} (a two-arm pattern) or by 90{\deg} (a four-arm pattern). We demonstrate that, for the inner region, the observations are best represented with a four-arm scheme of the spiral pattern, associated with all-Galaxy spiral density waves. The basic position is that of the Carina arm, reliably determined from distances to HII regions and from HI and H2 radial velocities. This pattern is continued in the quadrants III and IV with weak outer HI arms; from their morphology, the Galaxy should be considered an asymmetric multi-arm spiral. The kneed shape of the outer arms that consist of straight segments can indicate that these arms are transient formations that appeared due to a gravitational instability in the gas disk. The distances between HI superclouds in the two arms that are the brightest in neutral hydrogen, the Carina arm and the Cygnus (Outer) arm, concentrate to two values, permitting to assume the presence of a regular magnetic field in these arms.Comment: 21 pages, 14 fugures; accepted for publication in Astronomichesky Journal (Astron. Rep.

Effects of boundary conditions on magnetization switching in kinetic Ising models of nanoscale ferromagnets

Magnetization switching in highly anisotropic single-domain ferromagnets has been previously shown to be qualitatively described by the droplet theory of metastable decay and simulations of two-dimensional kinetic Ising systems with periodic boundary conditions. In this article we consider the effects of boundary conditions on the switching phenomena. A rich range of behaviors is predicted by droplet theory: the specific mechanism by which switching occurs depends on the structure of the boundary, the particle size, the temperature, and the strength of the applied field. The theory predicts the existence of a peak in the switching field as a function of system size in both systems with periodic boundary conditions and in systems with boundaries. The size of the peak is strongly dependent on the boundary effects. It is generally reduced by open boundary conditions, and in some cases it disappears if the boundaries are too favorable towards nucleation. However, we also demonstrate conditions under which the peak remains discernible. This peak arises as a purely dynamic effect and is not related to the possible existence of multiple domains. We illustrate the predictions of droplet theory by Monte Carlo simulations of two-dimensional Ising systems with various system shapes and boundary conditions.Comment: RevTex, 48 pages, 13 figure

High resolution global climate modelling; the UPSCALE project, a large simulation campaign

The UPSCALE (UK on PRACE: weather-resolving Simulations of Climate for globAL Environmental risk) project constructed and ran an ensemble of HadGEM3 (Hadley Centre Global Environment Model 3) atmosphere only global climate simulations over the period 1985–2011, at resolutions of N512 (25 km), N216 (60 km) and N96 (130 km) as used in current global weather forecasting, seasonal prediction and climate modelling respectively. Alongside these present climate simulations a parallel ensemble looking at extremes of future climate was run, using a timeslice methodology to consider conditions at the end of this century. These simulations were primarily performed using a 144 million core hour, single year grant of computing time from PRACE (the Partnership for Advanced Computing in Europe) in 2012, with additional resources supplied by the Natural Environment Research Council (NERC) and the Met Office. Almost 400 terabytes of simulation data were generated on the HERMIT supercomputer at the High Performance Computing Center Stuttgart (HLRS), and transferred to the JASMIN super-data cluster provided by the Science and Technology Facilities Council Centre for Data Archival (STFC CEDA) for analysis and storage. In this paper we describe the implementation of the project, present the technical challenges in terms of optimisation, data output, transfer and storage that such a project involves and include details of the model configuration and the composition of the UPSCALE data set. This data set is available for scientific analysis to allow assessment of the value of model resolution in both present and potential future climate conditions

A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of alpha-dystroglycan

Dystroglycan, an extracellular matrix receptor, has essential functions in various tissues. Loss of α‐dystroglycan‐laminin interaction due to defective glycosylation of α‐dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic human dystroglycanopathy cell models has limited our ability to test potential drugs in a human‐ and neural‐specific context. Here, we generated induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous FKRP (fukutin‐related protein gene) mutation. We showed that CRISPR/Cas9‐mediated gene correction of FKRP restored glycosylation of α‐dystroglycan in iPSC‐derived cortical neurons, whereas targeted gene mutation of FKRP in wild‐type cells disrupted this glycosylation. In parallel, we screened 31,954 small molecule compounds using a mouse myoblast line for increased glycosylation of α‐dystroglycan. Using human FKRP‐iPSC‐derived neural cells for hit validation, we demonstrated that compound 4‐(4‐bromophenyl)‐6‐ethylsulfanyl‐2‐oxo‐3,4‐dihydro‐1H‐pyridine‐5‐carbonitrile (4BPPNit) significantly augmented glycosylation of α‐dystroglycan, in part through upregulation of LARGE1 glycosyltransferase gene expression. Together, isogenic human iPSC‐derived cells represent a valuable platform for facilitating dystroglycanopathy drug discovery and therapeutic development

Interaction of Rio1 Kinase with Toyocamycin Reveals a Conformational Switch That Controls Oligomeric State and Catalytic Activity

Rio1 kinase is an essential ribosome-processing factor required for proper maturation of 40 S ribosomal subunit. Although its structure is known, several questions regarding its functional remain to be addressed. We report that both Archaeoglobus fulgidus and human Rio1 bind more tightly to an adenosine analog, toyocamycin, than to ATP. Toyocamycin has antibiotic, antiviral and cytotoxic properties, and is known to inhibit ribosome biogenesis, specifically the maturation of 40 S. We determined the X-ray crystal structure of toyocamycin bound to Rio1 at 2.0 Å and demonstrated that toyocamycin binds in the ATP binding pocket of the protein. Despite this, measured steady state kinetics were inconsistent with strict competitive inhibition by toyocamycin. In analyzing this interaction, we discovered that Rio1 is capable of accessing multiple distinct oligomeric states and that toyocamycin may inhibit Rio1 by stabilizing a less catalytically active oligomer. We also present evidence of substrate inhibition by high concentrations of ATP for both archaeal and human Rio1. Oligomeric state studies show both proteins access a higher order oligomeric state in the presence of ATP. The study revealed that autophosphorylation by Rio1 reduces oligomer formation and promotes monomerization, resulting in the most active species. Taken together, these results suggest the activity of Rio1 may be modulated by regulating its oligomerization properties in a conserved mechanism, identifies the first ribosome processing target of toyocamycin and presents the first small molecule inhibitor of Rio1 kinase activity

The archaeology of the military orders: the material culture of holy war

This paper reviews the current state of research into the archaeology of the military orders. It contrasts the advances made by historians and archaeologists, with the latter continuing to focus on the particularism of individual sites, with an emphasis on architectural analyses. Historians have contributed new insights by adopting a supranational approach. This paper argues that archaeologists can build on this by adopting a more problem-oriented, comparative approach. Drawing on examples from frontier and heartland territories, archaeological approaches are subdivided into material investment, material identity and cultural landscapes, to place sites of the military orders within a long-term, multi-scalar contexts. This contributes to a broader social and economic understanding of the orders, who contributed significantly to urbanisation, rural development and trade, and invested in material expressions of their authority and ideology. The paper concludes that more holistic, inter-regional approaches will move the archaeological study of the military orders forward