Ultra-light axions and the S8S_8 tension: joint constraints from the cosmic microwave background and galaxy clustering

We search for ultra-light axions as dark matter (DM) and dark energy particle candidates, for axion masses $10^{-32}\,\mathrm{eV} \leq m_\mathrm{a} \leq 10^{-24}\,\mathrm{eV}$, by a joint analysis of cosmic microwave background (CMB) and galaxy clustering data -- and consider if axions can resolve the tension in inferred values of the matter clustering parameter $S_8$. We give legacy constraints from Planck 2018 CMB data, improving 2015 limits on the axion density $\Omega_\mathrm{a} h^2$ by up to a factor of three; CMB data from the Atacama Cosmology Telescope and the South Pole Telescope marginally weaken Planck bounds at $m_\mathrm{a} = 10^{-25}\,\mathrm{eV}$, owing to lower (and theoretically-consistent) gravitational lensing signals. We jointly infer, from Planck CMB and full-shape galaxy power spectrum and bispectrum data from the Baryon Oscillation Spectroscopic Survey (BOSS), that axions are, today, $< 10\%$ of the DM for $m_\mathrm{a} \leq 10^{-26}\,\mathrm{eV}$ and $< 1\%$ for $10^{-30}\,\mathrm{eV} \leq m_\mathrm{a} \leq 10^{-28}\,\mathrm{eV}$. BOSS data strengthen limits, in particular at higher $m_\mathrm{a}$ by probing high-wavenumber modes ($k < 0.4 h\,\mathrm{Mpc}^{-1}$). BOSS alone finds a preference for axions at $2.7 \sigma$, for $m_\mathrm{a} = 10^{-26}\,\mathrm{eV}$, but Planck disfavours this result. Nonetheless, axions in a window $10^{-28}\,\mathrm{eV} \leq m_\mathrm{a} \leq 10^{-25}\,\mathrm{eV}$ can improve consistency between CMB and galaxy clustering data, e.g., reducing the $S_8$ discrepancy from $2.7 \sigma$ to $1.6 \sigma$, since these axions suppress structure growth at the $8 h^{-1}\,\mathrm{Mpc}$ scales to which $S_8$ is sensitive. We expect improved constraints with upcoming high-resolution CMB and galaxy lensing and future galaxy clustering data, where we will further assess if axions can restore cosmic concordance.Comment: 52 pages, 22 figure

Computer simulations of domain growth and phase separation in two-dimensional binary immiscible fluids using dissipative particle dynamics

We investigate the dynamical behavior of binary fluid systems in two dimensions using dissipative particle dynamics. We find that following a symmetric quench the domain size R(t) grows with time t according to two distinct algebraic laws R(t) = t^n: at early times n = 1/2, while for later times n = 2/3. Following an asymmetric quench we observe only n = 1/2, and if momentum conservation is violated we see n = 1/3 at early times. Bubble simulations confirm the existence of a finite surface tension and the validity of Laplace's law. Our results are compared with similar simulations which have been performed previously using molecular dynamics, lattice-gas and lattice-Boltzmann automata, and Langevin dynamics. We conclude that dissipative particle dynamics is a promising method for simulating fluid properties in such systems.Comment: RevTeX; 22 pages, 5 low-resolution figures. For full-resolution figures, connect to http://www.tcm.phy.cam.ac.uk/~ken21/tension/tension.htm

Tissue expression of PD-L1 mediates peripheral T cell tolerance

Programmed death 1 (PD-1), an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. PD-1 has two ligands: PD-1 ligand 1 (PD-L1), which is expressed broadly on hematopoietic and parenchymal cells, including pancreatic islet cells; and PD-L2, which is restricted to macrophages and dendritic cells. To investigate whether PD-L1 and PD-L2 have synergistic or unique roles in regulating T cell activation and tolerance, we generated mice lacking PD-L1 and PD-L2 (PD-L1/PD-L2−/− mice) and compared them to mice lacking either PD-L. PD-L1 and PD-L2 have overlapping functions in inhibiting interleukin-2 and interferon-γ production during T cell activation. However, PD-L1 has a unique and critical role in controlling self-reactive T cells in the pancreas. Our studies with bone marrow chimeras demonstrate that PD-L1/PD-L2 expression only on antigen-presenting cells is insufficient to prevent the early onset diabetes that develops in PD-L1/PD-L2−/− non-obese diabetic mice. PD-L1 expression in islets protects against immunopathology after transplantation of syngeneic islets into diabetic recipients. PD-L1 inhibits pathogenic self-reactive CD4+ T cell–mediated tissue destruction and effector cytokine production. These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1–PD-L1 interactions in mediating tissue tolerance

Spinodal decomposition of off-critical quenches with a viscous phase using dissipative particle dynamics in two and three spatial dimensions

We investigate the domain growth and phase separation of hydrodynamically-correct binary immiscible fluids of differing viscosity as a function of minority phase concentration in both two and three spatial dimensions using dissipative particle dynamics. We also examine the behavior of equal-viscosity fluids and compare our results to similar lattice-gas simulations in two dimensions.Comment: 34 pages (11 figures); accepted for publication in Phys. Rev.

Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study

AbstractBackgroundMany patients with chronic myeloid leukemia in chronic phase experience chronic treatment-related adverse events (AEs) during imatinib therapy. These AEs can impair quality of life and lead to reduced treatment adherence, which is associated with poor clinical outcomes.Patients and MethodsIn the phase II ENRICH (Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events) study (N = 52), the effect of switching patients with imatinib-related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated.ResultsThree months after switching to nilotinib, 84.6% of the patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% had resolved within 3 months of switching to nilotinib. Of evaluable patients, most had improvements in overall quality of life after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of the major molecular response was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported with nilotinib were typically grade 1 or 2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib because of new or worsening AEs.ConclusionOverall, results from the ENRICH study demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with chronic myeloid leukemia in chronic phase, in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018

PD-L1 regulates the development, maintenance, and function of induced regulatory T cells

Both the programmed death (PD) 1–PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg (iT reg) cell development and sustaining iT reg cell function. PD-L1−/− antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. PD-L1–coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1−/−PD-L2−/− Rag−/− recipients of naive CD4 T cells. PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Carpal tunnel syndrome and the use of computer mouse and keyboard: A systematic review

<p>Abstract</p> <p>Background</p> <p>This review examines evidence for an association between computer work and carpal tunnel syndrome (CTS).</p> <p>Methods</p> <p>A systematic review of studies of computer work and CTS was performed. Supplementary, longitudinal studies of low force, repetitive work and CTS, and studies of possible pathophysiological mechanisms were evaluated.</p> <p>Results</p> <p>Eight epidemiological studies of the association between computer work and CTS were identified. All eight studies had one or more limitation including imprecise exposure and outcome assessment, low statistical power or potentially serious biases. In three of the studies an exposure-response association was observed but because of possible misclassification no firm conclusions could be drawn. Three of the studies found risks below 1. Also longitudinal studies of repetitive low-force non-computer work (n = 3) were reviewed but these studies did not add evidence to an association. Measurements of carpal tunnel pressure (CTP) under conditions typically observed among computer users showed pressure values below levels considered harmful. However, during actual mouse use one study showed an increase of CTP to potentially harmful levels. The long term effects of prolonged or repeatedly increased pressures at these levels are not known, however.</p> <p>Conclusion</p> <p>There is insufficient epidemiological evidence that computer work causes CTS.</p

Structural Analysis of the Western Afar Margin, East Africa: Evidence for Multiphase Rotational Rifting

The Afar region in East Africa represents a key location to study continental breakup. We present an integrated structural analysis of the Western Afar Margin (WAM) aiming to better understand rifted margin development and the role of plate rotation during rifting. New structural information from remote sensing, fieldwork, and earthquake data sets reveals that the N-S striking WAM is still actively deforming and is characterized by NNW-SSE normal faulting as well as a series of marginal grabens. Seismicity distribution analysis and the first-ever borehole-calibrated sections of this developing passive margin show recent slip concentrated along antithetic faults. Tectonic stress parameters derived from earthquake focal mechanisms reveal different extension directions along the WAM (82°N), in Afar (66°N) and in the Main Ethiopian Rift (108°N). Fault slip analysis along the WAM yields the same extension direction. Combined with GPS data, this shows that current tectonics in Afar is dominated by the local rotation of the Danakil Block, considered to have occurred since 11 Ma. Earlier stages of Afar development (since 31–25 Ma) were most likely related to the large-scale rotation of the Arabian plate. Various authors have proposed scenarios for the evolution of the WAM. Any complete model should consider, among other factors, the multiphase tectonic history and antithetic fault activity of the margin. The findings of this study are not only relevant for a better understanding of the WAM but also provide insights into the role of multiphase rotational extension during rifting and passive margin formation in general.</p