Toward Perfection: Kapellasite, Cu3Zn(OH)6Cl2, a New Model S = 1/2 Kagome Antiferromagnet

The search for the resonating valence bond (RVB) state continues to underpin many areas of condensed matter research. The RVB is made from the dimerisation of spins on different sites into fluctuating singlets, and was proposed by Anderson to be the reference state from which the transition to BCS superconductivity occurs. Little is known about the state experimentally, due to the scarcity of model materials. Theoretical work has put forward the S = 1/2 kagome antiferromagnet (KAFM) as a good candidate for the realization of the RVB state. In this paper we introduce a new model system, the S = 1/2 KAFM Kapellasite, Cu3Zn(OH)6Cl2. We show that its crystal structure is a good approximation to a 2-dimensional kagome antiferromagnet and that susceptibility data indicate a collapse of the magnetic moment below T = 25 K that is compatible with the spins condensing into the non-magnetic RVB state.Comment: Communication, 3 pages, 3 figure

HCMV Antivirals and Strategies to Target the Latent Reservoir.

Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir

Bromodomain Inhibitors as Therapeutics for Herpesvirus-Related Disease: All BETs Are Off?

Although the ubiquitous human herpesviruses (HHVs) are rarely associated with serious disease of the healthy host, primary infection and reactivation in immunocompromised individuals can lead to significant morbidity and, in some cases, mortality. Effective drugs are available for clinical treatment, however resistance is on the rise such that new anti-viral targets, as well as novel clinical treatment strategies, are required. A promising area of development and pre-clinical research is that of inhibitors of epigenetic modifying proteins that control both cellular functions and the viral life cycle. Here, we briefly outline the interaction of the host bromo- and extra-terminal domain (BET) proteins during different stages of the HHVs' life cycles while giving a full overview of the published work using BET bromodomain inhibitors (BRDis) during HHV infections. Furthermore, we provide evidence that small molecule inhibitors targeting the host BET proteins, and BRD4 in particular, have the potential for therapeutic intervention of HHV-associated disease

Prototype Backscatter Moessbauer Spectrometer for Measurement of Martian Surface Mineralogy

We have designed and successfully tested a prototype of a backscatter Moessbauer spectrometer (BaMS) targeted for use on the Martian surface to (1) determine oxidation states of iron, and (2) identify and determine relative abundances of iron-bearing mineralogies. No sample preparation is required to perform measurements; it is only necessary to bring sample and instrument into physical contact. The prototype meets our projected specification for a flight instrument in terms of mass, power, and volume. A Moessbauer spectrometer on the Martian surface would provide wide variety of information about the current state of the Martian surface, and this information is described

On the Nature of Soft X-ray Weak Quasi-Stellar Objects

Recent studies of QSOs with ROSAT suggest the existence of a significant population of Soft X-ray Weak QSOs (SXW QSOs) where the soft X-ray flux is ~ 10-30 times smaller than in typical QSOs. As a first step in a systematic study of these objects, we establish a well-defined sample of SXW QSOs which includes all alpha_ox<=-2 QSOs from the Boroson & Green (1992) sample of 87 BQS QSOs. SXW QSOs comprise about 11% of this optically selected QSO sample. From an analysis of CIV absorption in the 55 BG92 QSOs with available CIV data, we find a remarkably strong correlation between alpha_ox and the CIV absorption equivalent width. This correlation suggests that absorption is the primary cause of soft X-ray weakness in QSOs, and it reveals a continuum of absorption properties connecting unabsorbed QSOs, X-ray warm absorber QSOs, SXW QSOs and BAL QSOs. From a practical point of view, our correlation demonstrates that selection by soft X-ray weakness is an effective (>=80% successful) and observationally inexpensive way to find low-redshift QSOs with strong and interesting ultraviolet absorption. We have also identified several notable differences between the optical emission-line properties of SXW QSOs and those of the other BG92 QSOs. SXW QSOs show systematically low [O III] luminosities as well as distinctive H-beta profiles. They tend to lie toward the weak-[O III] end of BG92 eigenvector 1, as do many low-ionization BAL QSOs. Unabsorbed Seyferts and QSOs with similar values of eigenvector 1 have been suggested to have extreme values of a primary physical parameter, perhaps mass accretion rate relative to the Eddington rate (M-dot/M-dot_{Edd}). If these suggestions are correct, it is likely that SXW QSOs also tend to have generally high values of (M-dot/M-dot_{Edd}). (Abridged)Comment: 34 pages, ApJ accepted, also available from http://www.astro.psu.edu/users/niel/papers/papers.htm

VLA H92 Alpha and H53 Alpha Radio Recombination Line Observations of M82

We present high angular resolution (0.6'') observations made with the VLA of the radio continuum at 8.3 and 43 GHz as well as H92 Alpha and H53 Alpha radio recombination lines from the nearby (3 Mpc) starburst galaxy M82. In the continuum we report 19 newly identified sources at 8.3 GHz and 5 at 43 GHz that were unknown previously. The spatial distribution of the H92 Alpha line is inhomogeneous; we identify 27 features. The line and continuum emission are modeled using a collection of HII regions at different distances from the nucleus assuming a single-density component and two-density components. The high-density component has a density of 4 X 10^{4} cm^{-3}. However, the bulk of the ionization is in regions with densities which are typically a factor 10 lower. The gas kinematics, using the H92 Alpha line, confirms the presence of steep velocity gradient (26 km s^{-1} arcsec^{-1}) in the nuclear region. As this steep gradient is observed not only on the major axis but also at large distances along a band of PA of 150 degrees, the interpretation in terms of x2 orbits elongated along the minor axis of the bar, which would be observed at an angle close to the inclination of the main disk, seems inadequate. Ad-hoc radial motions must be introduced to reproduce the pattern of the velocity field. Different families of orbits are indicated as we detect a signature in the kinematics at the transition between the two plateaus observed in the NIR light distribution. The H92 Alpha line also reveals the base of the outflow where the injection towards the halo on the Northern side occurs. The kinematical pattern suggests a connection between the gas flowing in the plane of M82 towards the center; this behavior most likely originates due to the presence of a bar and the outflow out of the plane.Comment: 45 pages, 11 figures and 6 tables. Accepted for publication in Ap

The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?

While the host immune response following primary human cytomegalovirus (HCMV) infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lytic infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. Reactivation from latency is also a major cause of HCMV-mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latently infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings.This work was funded by British Medical Research Council Grant JS and MW - G0701279 and MR/K021087/1 and supported by the NIHR Cambridge BRC Cell Phenotyping hub.This is the accepted manuscript. The final version is available from the publisher at http://www.nature.com/cmi/journal/vaop/ncurrent/full/cmi201475a.html

Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules.

The repertoire of peptides displayed at the cell surface by MHC I molecules is shaped by two intracellular peptide editors, tapasin and TAPBPR. While cell-free assays have proven extremely useful in identifying the function of both of these proteins, here we explored whether a more physiological system could be developed to assess TAPBPR-mediated peptide editing on MHC I. We reveal that membrane-associated TAPBPR targeted to the plasma membrane retains its ability to function as a peptide editor and efficiently catalyzes peptide exchange on surface-expressed MHC I molecules. Additionally, we show that soluble TAPBPR, consisting of the luminal domain alone, added to intact cells, also functions as an effective peptide editor on surface MHC I molecules. Thus, we have established two systems in which TAPBPR-mediated peptide exchange on MHC class I can be interrogated. Furthermore, we could use both plasma membrane-targeted and exogenous soluble TAPBPR to display immunogenic peptides on surface MHC I molecules and consequently induce T cell receptor engagement, IFN-γ secretion, and T cell-mediated killing of target cells. Thus, we have developed an efficient way to by-pass the natural antigen presentation pathway of cells and load immunogenic peptides of choice onto cells. Our findings highlight a potential therapeutic use for TAPBPR in increasing the immunogenicity of tumors in the future

Spin dynamics and disorder effects in the S=1/2 kagome Heisenberg spin liquid phase of kapellasite

We report $^{35}$Cl NMR, ESR, $\mu$SR and specific heat measurements on the $S=1/2$ frustrated kagom\'e magnet kapellasite, $\alpha-$Cu$_3$Zn(OH)$_6$Cl$_2$, where a gapless spin liquid phase is stabilized by a set of competing exchange interactions. Our measurements confirm the ferromagnetic character of the nearest-neighbour exchange interaction $J_1$ and give an energy scale for the competing interactions $|J| \sim 10$ K. The study of the temperature-dependent ESR lineshift reveals a moderate symmetric exchange anisotropy term $D$, with $|D/J|\sim 3$%. These findings validate a posteriori the use of the $J_1 - J_2 - J_d$ Heisenberg model to describe the magnetic properties of kapellasite [Bernu et al., Phys. Rev. B 87, 155107 (2013)]. We further confirm that the main deviation from this model is the severe random depletion of the magnetic kagom\'e lattice by 27%, due to Cu/Zn site mixing, and specifically address the effect of this disorder by $^{35}$Cl NMR, performed on an oriented polycrystalline sample. Surprisingly, while being very sensitive to local structural deformations, our NMR measurements demonstrate that the system remains homogeneous with a unique spin susceptibility at high temperature, despite a variety of magnetic environments. Unconventional spin dynamics is further revealed by NMR and $\mu$SR in the low-$T$, correlated, spin liquid regime, where a broad distribution of spin-lattice relaxation times is observed. We ascribe this to the presence of local low-energy modes.Comment: 15 pages, 11 figures. To appear in Phys. Rev.