Clustering in Block Markov Chains

This paper considers cluster detection in Block Markov Chains (BMCs). These Markov chains are characterized by a block structure in their transition matrix. More precisely, the $n$ possible states are divided into a finite number of $K$ groups or clusters, such that states in the same cluster exhibit the same transition rates to other states. One observes a trajectory of the Markov chain, and the objective is to recover, from this observation only, the (initially unknown) clusters. In this paper we devise a clustering procedure that accurately, efficiently, and provably detects the clusters. We first derive a fundamental information-theoretical lower bound on the detection error rate satisfied under any clustering algorithm. This bound identifies the parameters of the BMC, and trajectory lengths, for which it is possible to accurately detect the clusters. We next develop two clustering algorithms that can together accurately recover the cluster structure from the shortest possible trajectories, whenever the parameters allow detection. These algorithms thus reach the fundamental detectability limit, and are optimal in that sense.Comment: 73 pages, 18 plots, second revisio

Fidelity of optimally controlled quantum gates with randomly coupled multiparticle environments

This work studies the feasibility of optimal control of high-fidelity quantum gates in a model of interacting two-level particles. One particle (the qubit) serves as the quantum information processor, whose evolution is controlled by a time-dependent external field. The other particles are not directly controlled and serve as an effective environment, coupling to which is the source of decoherence. The control objective is to generate target one-qubit gates in the presence of strong environmentally-induced decoherence and under physically motivated restrictions on the control field. It is found that interactions among the environmental particles have a negligible effect on the gate fidelity and require no additional adjustment of the control field. Another interesting result is that optimally controlled quantum gates are remarkably robust to random variations in qubit-environment and inter-environment coupling strengths. These findings demonstrate the utility of optimal control for management of quantum-information systems in a very precise and specific manner, especially when the dynamics complexity is exacerbated by inherently uncertain environmental coupling.Comment: tMOP LaTeX, 9 pages, 3 figures; Special issue of the Journal of Modern Optics: 37th Winter Colloquium on the Physics of Quantum Electronics, 2-6 January 200

Vigorous star formation hidden by dust in a galaxy at z=1.4z=1.4

Near-infrared surveys have revealed a substantial population of enigmatic faint galaxies with extremely red optical-to-near-infrared colours and with a sky surface density comparable to that of faint quasars. There are two scenarios for these extreme colours: (i) these distant galaxies have formed virtually all their stars at very high redshifts and, due to the absence of recently formed stars, the colours are extremely red and (ii) these distant galaxies contain large amounts of dust, severely reddening the rest-frame UV--optical spectrum. HR10 ($z = 1.44$) is considered the archetype of the extremely red galaxies. Here we report the detection of the continuum emission from HR10 at 850$\mu$m and at 1250$\mu$m, demonstrating that HR10 is a very dusty galaxy undergoing a major episode of star formation. Our result provides a clear example of a high-redshift galaxy where the star formation rate inferred from the ultraviolet luminosity would be underestimated by a factor up to 1000, and shows that great caution should be used to infer the global star formation history of the Universe from optical observations only.Comment: 12 pages, 1 figure, Nature, in press (30 April 1998

HTLV-1 basic leucine zipper factor protects cells from oxidative stress by upregulating expression of Heme Oxygenase I

Adult T-cell Leukemia (ATL) is a lymphoproliferative disease of CD4+ T-cells infected with Human T-cell Leukemia Virus type I (HTLV-1). With the exception of allogeneic hematopoietic stem cell transplantation, there are no effective treatments to cure ATL, and ATL cells often acquire resistance to conventional chemotherapeutic agents. Accumulating evidence shows that development and maintenance of ATL requires key contributions from the viral protein, HTLV-1 basic leucine zipper factor (HBZ). In this study we found that HBZ activates expression of Heme Oxygenase 1 (HMOX-1), a component of the oxidative stress response that functions to detoxify free heme. Transcription of HMOX1 and other antioxidant genes is regulated by the small Mafs. These cellular basic leucine zipper (bZIP) factors control transcription by forming homo- or heterodimers among themselves or with other cellular bZIP factors that then bind Maf responsive elements (MAREs) in promoters or enhancers of antioxidant genes. Our data support a model in which HBZ activates HMOX1 transcription by forming heterodimers with the small Mafs that bind MAREs located in an upstream enhancer region. Consistent with this model, we found that HMOX-1 is upregulated in HTLV-1-transformed T-cell lines and confers these cells with resistance to heme-induced cytotoxicity. In this context, HBZ-mediated activation of HMOX-1 expression may contribute to resistance of ATL cells to certain chemotherapeutic agents. We also provide evidence that HBZ counteracts oxidative stress caused by two other HTLV-1-encoded proteins, Tax and p13. Tax induces oxidative stress as a byproduct of driving mitotic expansion of infected cells, and p13 is believed to induce oxidative stress to eliminate infected cells that have become transformed. Therefore, in this context, HBZ-mediated activation of HMOX-1 expression may facilitate transformation. Overall, this study characterizes a novel function of HBZ that may support the development and maintenance of ATL

The Milky Way Halo in Action Space

We analyze the structure of the local stellar halo of the Milky Way using ~60000 stars with full phase space coordinates extracted from the SDSS–Gaia catalog. We display stars in action space as a function of metallicity in a realistic axisymmetric potential for the Milky Way Galaxy. The metal-rich population is more distended toward high radial action J R as compared to azimuthal or vertical action, J phgr or J z . It has a mild prograde rotation $(\langle {v}_{\phi }\rangle \approx 25\,\mathrm{km}\,{{\rm{s}}}^{-1}$), is radially anisotropic and highly flattened, with axis ratio q ≈ 0.6–0.7. The metal-poor population is more evenly distributed in all three actions. It has larger prograde rotation $(\langle {v}_{\phi }\rangle \approx 50\,\mathrm{km}\,{{\rm{s}}}^{-1}$), a mild radial anisotropy, and a roundish morphology (q ≈ 0.9). We identify two further components of the halo in action space. There is a high-energy, retrograde component that is only present in the metal-rich stars. This is suggestive of an origin in a retrograde encounter, possibly the one that created the stripped dwarf galaxy nucleus, ωCentauri. Also visible as a distinct entity in action space is a resonant component, which is flattened and prograde. It extends over a range of metallicities down to [Fe/H] ≈ −3. It has a net outward radial velocity $\langle {v}_{R}\rangle \approx 12\,\mathrm{km}\,{{\rm{s}}}^{-1}$ within the solar circle at $| z| \lt 3.5\,\mathrm{kpc}$. The existence of resonant stars at such extremely low metallicities has not been seen before.G.C.M. thanks the Boustany Foundation, Cambridge Commonwealth, European & International Trust and Isaac Newton Studentship for their support of his work. J.L.S. thanks the Science and Technology Facilities Council for financial support. The research leading to these results has received partial support from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant agreement No. 308024. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium). Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement

Discovery of new retrograde substructures: The shards of ω Centauri?

We use the Sloan Digital Sky Survey (SDSS)-Gaia catalogue to search for substructure in the stellar halo. The sample comprises 62 133 halo stars with full phase space coordinates and extends out to heliocentric distances of ~10 kpc. As actions are conserved under slow changes of the potential, they permit identification of groups of stars with a common accretion history. We devise a method to identify halo substructures based on their clustering in action space, using metallicity as a secondary check. This is validated against smooth models and numerical constructed stellar haloes from the Aquarius simulations. We identify 21 substructures in the SDSS-Gaia catalogue, including seven high-significance, high-energy and retrograde ones. We investigate whether the retrograde substructures may be material stripped offthe atypical globular cluster ω Centauri. Using a simple model of the accretion of the progenitor of the ω Centauri, we tentatively argue for the possible association of up to five of our new substructures (labelled Rg1, Rg3, Rg4, Rg6 and Rg7) with this event. This sets a minimum mass of 5 × 108M⊙ for the progenitor, so as to bring ω Centauri to its current location in action-energy space. Our proposal can be tested by high-resolution spectroscopy of the candidates to look for the unusual abundance patterns possessed by ω Centauri stars

The Sausage Globular Clusters

The Gaia Sausage is an elongated structure in velocity space discovered by Belokurov et al. using the kinematics of metal-rich halo stars. They showed that it could be created by a massive dwarf galaxy (∼5 1010 ) on a strongly radial orbit that merged with the Milky Way at a redshift z ≲ 3. This merger would also have brought in globular clusters (GCs). We seek evidence for the associated Sausage Globular Clusters (GCs) by analyzing the structure of 91 Milky Way GCs in action space using the Gaia Data Release 2 catalog, complemented with Hubble Space Telescope proper motions. There is a characteristic energy that separates the in situ objects, such as the bulge/disk clusters, from the accreted objects, such as the young halo clusters. There are 15 old halo GCs that have E > . Eight of the high-energy, old halo GCs are strongly clumped in azimuthal and vertical action, yet strung out like beads on a chain at extreme radial action. They are very radially anisotropic (β ∼ 0.95) and move on orbits that are all highly eccentric (e 0.80). They also form a track in the age-metallicity plane compatible with a dwarf galaxy origin. These properties are consistent with GCs associated with the merger event that gave rise to the Gaia Sausage

Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review

Introduction: Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilisation of ART for immediate treatment and prevention of HIV infection. Discussion: Missed acute HIV infection prevents people living with HIV (PLWH) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. Whilst immediate ART is recommended for all PLWH, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As roll-out of PrEP continues, HIV testing algorithms may need to be modified. Conclusions: With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance is needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable

VVV-WIT-08: the giant star that blinked

We report the serendipitous discovery of a late-type giant star that exhibited a smooth, eclipse-like drop in flux to a depth of 97 per cent. Minimum flux occurred in 2012 April and the total event duration was a few hundred days. Light curves in V, I, and Ks from the Optical Gravitational Lensing Experiment and VISTA Variables in the Via Lactea surveys show a remarkably achromatic event. During 17 yr of observational coverage of this source only one such event was detected. The physical properties of the giant star itself appear somewhat unusual, which may ultimately provide a clue towards the nature of the system. By modelling the event as an occultation by an object that is elliptical in projection with uniform transparency, we place limits on its physical size and velocity. We find that the occultation is unlikely to be due to a chance alignment with a foreground object. We consider a number of possible candidates for the occulter, which must be optically thick and possess a radius or thickness in excess of 0.25 au. None are completely satisfactory matches to all the data. The duration, depth, and relative achromaticity of the dip mark this out as an exceptionally unusual event, whose secret has still not been fully revealed. We find two further candidates in the VVV survey and we suggest that these systems, and two previously known examples, may point to a broad class of long-period eclipsing binaries wherein a giant star is occulted by a circumsecondary disc

Paracellular permeability is increased by basal lipopolysaccharide in a primary culture of colonic epithelial cells; an effect prevented by an activator of Toll-like receptor-2

Lipopolysaccharide (LPS), which generally activates Toll-like receptor 4 (TLR4), is expressed on commensal colonic bacteria. In a number of tissues, LPS can act directly on epithelial cells to increase paracellular permeability. Such an effect in the colon would have an important impact on the understanding of normal homeostasis and of pathology. Our aim was to use a novel primary culture of colonic epithelial cells grown on Transwells to investigate whether LPS, or Pam(3)CSK( 4), an activator of TLR2, affected paracellular permeability. Consequently, [(14)C]-mannitol transfer and transepithelial electrical resistance (TEER) were measured. The preparation consisted primarily of cytokeratin-18 positive epithelial cells that produced superoxide, stained for mucus with periodic acid-Schiff reagent, exhibited alkaline phosphatase activity and expressed TLR2 and TLR4. Tight junctions and desmosomes were visible by transmission electron microscopy. Basally, but not apically, applied LPS from Escherichia coli increased the permeability to mannitol and to a 10-kDa dextran, and reduced TEER. The LPS from Helicobacter pylori increased paracellular permeability of gastric cells when applied either apically or basally, in contrast to colon cells, where this LPS was active only from the basal aspect. A pan-caspase inhibitor prevented the increase in caspase activity caused by basal E. coli LPS, and reduced the effects of LPS on paracellular permeability. Synthetic Pam(3)CSK(4) in the basal compartment prevented all effects of basal E. coli LPS. In conclusion, LPS applied to the base of the colonic epithelial cells increased paracellular permeability by a mechanism involving caspase activation, suggesting a process by which perturbation of the gut barrier could be exacerbated. Moreover, activation of TLR2 ameliorated such effects