We present a consistent low energy effective field theory framework for parametrizing the effects of novel short distance physics in inflation, and their possible observational signatures in the cosmic microwave background. We consider the class of general homogeneous, isotropic initial states for quantum scalar fields in Robertson-Walker (RW) spacetimes, subject to the requirement that their ultraviolet behavior be consistent with renormalizability of the covariantly conserved stress tensor which couples to gravity. In the functional Schrödinger picture such states are coherent, squeezed, mixed states characterized by a Gaussian density matrix. This Gaussian has parameters which approach those of the adiabatic vacuum at large wave number, and evolve in time according to an effective classical Hamiltonian. The one complex parameter family of $\alpha$ squeezed states in de Sitter spacetime does not fall into this UV allowed class, except for the special value of the parameter corresponding to the Bunch-Davies state. We determine the finite contributions to the inflationary power spectrum and stress tensor expectation value of general UV allowed adiabatic states, and obtain quantitative limits on the observability and backreaction effects of some recently proposed models of short distance modifications of the initial state of inflation. For all UV allowed states, the second order adiabatic basis provides a good description of particles created in the expanding RW universe. Because of the absence of particle creation for the massless, minimally coupled scalar field in de Sitter space, there is no phase decoherence in the simplest free field inflationary models. We apply adiabatic regularization to the renormalization of the decoherence functional in cosmology to corroborate this result.

Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum-sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to “count” the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4⁺ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4⁺ T cells and sensed by a population of CD4⁺ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4⁺ T cells and the total CD4⁺ T cell population. In other words, CD4⁺ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the key role of IL-2 and quorum-sensing mechanisms in CD4⁺ T cell homeostasis during an immune response.

Linearized fluctuations of quantized matter fields and the spacetime geometry around de Sitter space are considered in the case that the matter fields are conformally invariant. Taking the unperturbed state of the matter to be the de Sitter invariant Bunch-Davies state, the linear variation of the stress tensor about its self-consistent mean value serves as a source for fluctuations in the geometry through the semiclassical Einstein equations. This linear response framework is used to investigate both the importance of quantum backreaction and the validity of the semiclassical approximation in cosmology. The full variation of the stress tensor $\delta ⟨T^a{}_b⟩$ contains two kinds of terms: (1) those that depend explicitly upon the linearized metric variation $\delta g_{cd}$ through the $⟨[T^a{}_b,T^{cd}]⟩$ causal response function; and (2) state dependent variations, independent of $\delta g_{cd}$. For perturbations of the first kind, the criterion for the validity of the semiclassical approximation in de Sitter space is satisfied for fluctuations on all scales well below the Planck scale. The perturbations of the second kind contain additional massless scalar degrees of freedom associated with changes of state of the fields on the cosmological horizon scale. These scalar degrees of freedom arise necessarily from the local auxiliary field form of the effective action associated with the trace anomaly, are potentially large on the horizon scale, and therefore can lead to substantial nonlinear quantum backreaction effects in cosmology.

Cells of the mature $\alpha\beta$~T~cell repertoire arise from the development in the thymus of bone marrow precursors (thymocytes). $\alpha\beta$~T~cell maturation is characterised by the expression of thousands of copies of identical $\alpha\beta$~T~cell receptors and the CD4 and/or CD8~co-receptors on the surface of thymocytes. The maturation stages of a thymocyte are: (1) double negative (DN) (TCR$^{-}$, CD4$^{-}$ and CD8$^{-}$), (2) double positive (DP) (TCR$^{+}$, CD4$^{+}$ and CD8$^{+}$), and (3) single positive (SP) (TCR$^{+}$, CD4$^{+}$ or CD8$^{+}$). Thymic antigen presenting cells provide the appropriate micro-architecture for the maturation of thymocytes, which ``sense'' the signalling environment via their randomly generated TCRs. Thymic development is characterised by (i) an extremely low success rate, and (ii) the selection of a functional and self-tolerant T~cell repertoire. In this paper, we combine recent experimental data and mathematical modelling to study the selection events that take place in the thymus after the DN stage. The stable steady state of the model for the pre-DP, post-DP and SP populations is identified with the experimentally measured cell counts from 5.5-17 week old mice. We make use of residence times in the cortex and medulla for the different populations, as well as recently reported asymmetric death rates for CD4 and CD8 SP thymocytes. We estimate that 65.8\% of pre-DP thymocytes undergo death by neglect. In the post-DP compartment, 91.7\% undergo death by negative selection, 4.7\% become CD4 SP and 3.6\% become CD8 SP. Death by negative selection in the medulla removes 8.6\% of CD4 SP and 32.1\% of CD8 SP thymocytes, respectively. Approximately 46.3\% of CD4 SP and 27\% of CD8 SP thymocytes divide before dying or exiting the thymus.

Cytokines elicit pleiotropic and non-redundant activities despite strong overlap in their usage of receptors, JAKs and STATs molecules. We use IL-6 and IL-27 to ask how two cytokines activating the same signaling pathway have different biological roles. We found that IL-27 induces more sustained STAT1 phosphorylation than IL-6, with the two cytokines inducing comparable levels of STAT3 phosphorylation. Mathematical and statistical modeling of IL-6 and IL-27 signaling identified STAT3 binding to GP130, and STAT1 binding to IL-27Rα, as the main dynamical processes contributing to sustained pSTAT1 levels by IL-27. Mutation of Tyr613 on IL-27Rα decreased IL-27-induced STAT1 phosphorylation by 80% but had limited effect on STAT3 phosphorgylation. Strong receptor/STAT coupling by IL-27 initiated a unique gene expression program, which required sustained STAT1 phosphorylation and IRF1 expression and was enriched in classical Interferon Stimulated Genes. Interestingly, the STAT/receptor coupling exhibited by IL-6/IL-27 was altered in patients with systemic lupus erythematosus (SLE). IL-6/IL-27 induced a more potent STAT1 activation in SLE patients than in healthy controls, which correlated with higher STAT1 expression in these patients. Partial inhibition of JAK activation by sub-saturating doses of Tofacitinib specifically lowered the levels of STAT1 activation by IL-6. Our data show that receptor and STATs concentrations critically contribute to shape cytokine responses and generate functional pleiotropy in health and disease.