Проспекты АТ НДІ «РИФ - Акваапарат»

Abstract Most vaccines and basic studies of T cell epitopes in Mycobacterium tuberculosis emphasize water-soluble proteins that are secreted into the extracellular space and presented in the context of MHC class II. Much less is known about the role of Ags retained within the cell wall. We used polyclonal T cells from infected humans to probe for responses to immunodominant Ags in the M. tuberculosis cell wall. We found that the magnitude of response to secreted or cell wall intrinsic compounds was similar among healthy controls, patients with latent tuberculosis, and patients with active tuberculosis. Individual responses to secreted Ags and cell wall extract were strongly correlated (r2 = 0.495, p = 0.001), suggesting that T cells responding to cell wall and secreted Ags are present at similar frequency. Surprisingly, T cell stimulatory factors intrinsic to the cell wall partition into organic solvents; however, these responses are not explained by CD1-mediated presentation of lipids. Instead, we find that molecules soluble in organic solvents are dependent upon MHC class II and recognized by IFN-γ–secreting CD4+ T cells. We reasoned that MHC class II–dependent Ags extracting into lipid mixtures might be found among triacylated lipoproteins present in mycobacteria. We used M. tuberculosis lacking prolipoprotein signal peptidase A (lspA), an enzyme required for lipoprotein synthesis, to demonstrate loss of polyclonal T cell responses. Our results demonstrate the use of bacterial genetics to identify lipoproteins as an unexpected and immunodominant class of cell wall–associated Ags targeted by the polyclonal human T cell response to M. tuberculosis.</jats:p

Hyperbolic billiards of pure D=4 supergravities

We compute the billiards that emerge in the Belinskii-Khalatnikov-Lifshitz (BKL) limit for all pure supergravities in D=4 spacetime dimensions, as well as for D=4, N=4 supergravities coupled to k (N=4) Maxwell supermultiplets. We find that just as for the cases N=0 and N=8 investigated previously, these billiards can be identified with the fundamental Weyl chambers of hyperbolic Kac-Moody algebras. Hence, the dynamics is chaotic in the BKL limit. A new feature arises, however, which is that the relevant Kac-Moody algebra can be the Lorentzian extension of a twisted affine Kac-Moody algebra, while the N=0 and N=8 cases are untwisted. This occurs for N=5, N=3 and N=2. An understanding of this property is provided by showing that the data relevant for determining the billiards are the restricted root system and the maximal split subalgebra of the finite-dimensional real symmetry algebra characterizing the toroidal reduction to D=3 spacetime dimensions. To summarize: split symmetry controls chaos.Comment: 21 page

Travelling and sticky affects: : Exploring teens and sexualized cyberbullying through a Butlerian-Deleuzian- Guattarian lens

In this paper we combine the thinking of Deleuze and Guattari (1984, 1987) with Judith Butler’s (1990, 1993, 2004, 2009) work to follow the rhizomatic becomings of young people’s affective relations in a range of on- and off-line school spaces. In particular we explore how events that may be designated as sexual cyberbullying are constituted and how they are mediated by technology (such as texting or in/through social networking sites). Drawing on findings from two different studies looking at teens’ uses of and experiences with social networking sites, Arto in Denmark, and Bebo in the UK, we use this approach to think about how affects flow, are distributed, and become fixed in assemblages. We map how affects are manoeuvred and potentially disrupted by young people, suggesting that in the incidences discussed affects travel as well as stick in points of fixation. We argue that we need to grasp both affective flow and fixity in order to gain knowledge of how subjectification of the gendered/classed/racialised/sexualised body emerges. A Butlerian-Deleuzian-Guattarian frame helps us to map some of these affective complexities that shape sexualized cyberbully events; and to recognize technologically mediated lines of flight when subjectifications are at least temporarily disrupted and new terms of recognition and intelligibility staked out. Keywords

Hard-Sphere Fluids in Contact with Curved Substrates

The properties of a hard-sphere fluid in contact with hard spherical and cylindrical walls are studied. Rosenfeld's density functional theory (DFT) is applied to determine the density profile and surface tension $\gamma$ for wide ranges of radii of the curved walls and densities of the hard-sphere fluid. Particular attention is paid to investigate the curvature dependence and the possible existence of a contribution to $\gamma$ that is proportional to the logarithm of the radius of curvature. Moreover, by treating the curved wall as a second component at infinite dilution we provide an analytical expression for the surface tension of a hard-sphere fluid close to arbitrary hard convex walls. The agreement between the analytical expression and DFT is good. Our results show no signs for the existence of a logarithmic term in the curvature dependence of $\gamma$.Comment: 15 pages, 6 figure

Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells

Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity-mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals

Modern temporal network theory: A colloquium

The power of any kind of network approach lies in the ability to simplify a complex system so that one can better understand its function as a whole. Sometimes it is beneficial, however, to include more information than in a simple graph of only nodes and links. Adding information about times of interactions can make predictions and mechanistic understanding more accurate. The drawback, however, is that there are not so many methods available, partly because temporal networks is a relatively young field, partly because it more difficult to develop such methods compared to for static networks. In this colloquium, we review the methods to analyze and model temporal networks and processes taking place on them, focusing mainly on the last three years. This includes the spreading of infectious disease, opinions, rumors, in social networks; information packets in computer networks; various types of signaling in biology, and more. We also discuss future directions.Comment: Final accepted versio