Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection.

Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics study was performed in quintuplicate containing a total of 15 individual serum samples per group. Peptides were analyzed in an LC-Orbitrap Elite platform, and raw data were processed using Proteome Discoverer 2.1. A total of 418 proteins were quantified. The specific protein signature of active TB patients was characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response and also by a decrease of a small subset of proteins, including apolipoprotein A and serotransferrin, indicating the importance of lipid transport and iron assimilation in the progression of the disease. This signature was verified by the targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques. These findings will aid our understanding of the complex metabolic processes associated with TB progression from LTBI to active disease

Quarkonium dissociation by anisotropy

We compute the screening length for quarkonium mesons moving through an anisotropic, strongly coupled N=4 super Yang-Mills plasma by means of its gravity dual. We present the results for arbitrary velocities and orientations of the mesons, as well as for arbitrary values of the anisotropy. The anisotropic screening length can be larger or smaller than the isotropic one, and this depends on whether the comparison is made at equal temperatures or at equal entropy densities. For generic motion we find that: (i) mesons dissociate above a certain critical value of the anisotropy, even at zero temperature; (ii) there is a limiting velocity for mesons in the plasma, even at zero temperature; (iii) in the ultra-relativistic limit the screening length scales as $(1-v^2)^\epsilon$ with \epsilon =1/2, in contrast with the isotropic result \epsilon =1/4.Comment: 39 pages, 26 figures; v2: minor changes, added reference

Black Hole Deconstruction

A D4-D0 black hole can be deconstructed into a bound state of D0 branes with a D6-anti-D6 pair containing worldvolume fluxes. The exact spacetime solution is known and resembles a D0 accretion disk surrounding a D6-anti-D6 core. We find a scaling limit in which the disk and core drop inside an AdS_2 throat. Crossing this AdS_2 throat and the D0 accretion disk into the core, we find a second scaling region describing the D6-anti-D6 pair. It is shown that the M-theory lift of this region is AdS_3 x S^2. Surprisingly, time translations in the far asymptotic region reduce to global, rather than Poincare, time translations in this core AdS_3. We further find that the quantum mechanical ground state degeneracy reproduces the Bekenstein-Hawking entropy-area law.Comment: 11 page

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer’s disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system’s integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Massive Quantum Liquids from Holographic Angel's Trumpets

We explore the small-temperature regime in the deconfined phase of massive fundamental matter at finite baryon number density coupled to the 3+1 dimensional N=4 SYM theory. In this setting, we can demonstrate a new type of non-trivial temperature-independent scaling solutions for the probe brane embeddings. Focusing mostly on matter supported in 2+1 dimensions, the thermodynamics indicate that there is a quantum liquid with interesting density-dependent low-temperature physics. We also comment about 3+1 and 1+1 dimensional systems, where we further find for example a new thermodynamic instability.Comment: 18+1 pages, 6 figures; replaced fig. 6 and comments in sec. 5.2; minor explanations added and typos fixed, final version published in JHEP (modulo fig. 3); factor of \sqrt{\lambda} and corresponding comments fixe

Jet quenching in a strongly coupled anisotropic plasma

The jet quenching parameter of an anisotropic plasma depends on the relative orientation between the anisotropic direction, the direction of motion of the parton, and the direction along which the momentum broadening is measured. We calculate the jet quenching parameter of an anisotropic, strongly coupled N=4 plasma by means of its gravity dual. We present the results for arbitrary orientations and arbitrary values of the anisotropy. The anisotropic value can be larger or smaller than the isotropic one, and this depends on whether the comparison is made at equal temperatures or at equal entropy densities. We compare our results to analogous calculations for the real-world quark-gluon plasma and find agreement in some cases and disagreement in others.Comment: 22 pages, 10 figures; v2: minor changes, added reference. Extends arXiv:1202.369

Holographic Roberge-Weiss Transitions

We investigate N=4 SYM coupled to fundamental flavours at nonzero imaginary quark chemical potential in the strong coupling and large N limit, using gauge/gravity duality applied to the D3-D7 system, treating flavours in the probe approximation. The interplay between Z(N) symmetry and the imaginary chemical potential yields a series of first-order Roberge-Weiss transitions. An additional thermal transition separates phases where quarks are bound/unbound into mesons. This results in a set of Roberge-Weiss endpoints: we establish that these are triple points, determine the Roberge-Weiss temperature, give the curvature of the phase boundaries and confirm that the theory is analytic in mu^2 when mu^2~0.Comment: 37 pages, 13 figures; minor comments added, to appear in JHE

Physical Response Functions of Strongly Coupled Massive Quantum Liquids

We study physical properties of strongly coupled massive quantum liquids from their spectral functions using the AdS/CFT correspondence. The generic model that we consider is dense, heavy fundamental matter coupled to SU(N_c) super Yang-Mills theory at finite temperature above the deconfinement phase transition but below the scale set by the baryon number density. In this setup, we study the current-current correlators of the baryon number density using new techniques that employ a scaling behavior in the dual geometry. Our results, the AC conductivity, the quasi-particle spectrum and the Drude-limit parameters like the relaxation time are simple temperature-independent expressions that depend only on the mass-squared to density ratio and display a crossover between a baryon- and meson-dominated regime. We concentrated on the (2+1)-dimensional defect case, but in principle our results can also be generalized straightforwardly to other cases.Comment: 21 pages, 10 figures, extra paragraph and figure are added in response to referee's comment

Quasinormal modes of massive charged flavor branes

We present an analysis and classification of vector and scalar fluctuations in a D3/D7 brane setup at finite termperature and baryon density. The system is dual to an N=2 supersymmetric Yang-Mills theory with SU(N_c) gauge group and N_f hypermultiplets in the fundamental representation in the quenched approximation. We improve significantly over previous results on the quasinormal mode spectrum of D7 branes and stress their novel physical interpretation. Amongst our findings is a new purely imaginary scalar mode that becomes tachyonic at sufficiently low temperature and baryon density. We establish the existence of a critical density above which the scalar mode stays in the stable regime for all temperatures. In the vector sector we study the crossover from the hydrodynamic to the quasiparticle regime and find that it moves to shorter wavelengths for lower temperatures. At zero baryon density the quasinormal modes move toward distinct discrete attractor frequencies that depend on the momentum as we increase the temperature. At finite baryon density, however, the trajectories show a turning behavior such that for low temperature the quasinormal mode spectrum approaches the spectrum of the supersymmetric zero temperature normal modes. We interpret this as resolution of the singular quasinormal mode spectrum that appears at the limiting D7 brane embedding at vanishing baryon density.Comment: 56 pages, 40 figure