Bias of the Immune Response to \u3ci\u3ePneumocystis murina\u3c/i\u3e Does Not Alter the Ability of Neonatal Mice to Clear the Infection

Newborn mice are unable to clear Pneumocystis (PC) infection with the same efficiency as adults due, in part, to their inability to develop a robust immune response to infection until three weeks of age. It is known that infants tend develop a Th2 skewed response to antigen so we sought to determine whether a biased cytokine response altered the clearance of PC infection in neonatal mice. P. murina infection in neonatal mice resulted in increased IL-4 expression by CD4 T cells and myeloid cells, augmented IL-13 secretion within the airways and increased arginase activity in the airways, indicative of Th2-type responses. P. murina-infected IL-4Rα−/− neonates had a shift towards Th1 cytokine production and increased numbers of CD4 and CD8 T cells within the lung as well as elevated levels of P. murina-specific IgG. IFNγ−/− and IL-23 p19−/− mice had altered CD4-T cell-dependent cytokine and cell responses. Though we could alter the T helper cell environment in neonatal knockout mice, there was no loss in the ability of these pups to clear infection. It is possible that the Th2 phenotype normally seen in neonatal mice protects the developing lung from pro-inflammatory immune responses without compromising host defense against P. murina

Down syndrome with microgranular variant of acute promyelocytic leukemia in a child: a case report

<p>Abstract</p> <p>Background</p> <p>Acute promyelocytic leukemia (APL) accounts for less than 10% of pediatric AML. Cases of APL in Down syndrome (DS) have been described in the literature rarely and it is rarer still to find the microgranular variant (M3v) of APL in trisomy 21 patients.</p> <p>Case presentation</p> <p>We present a case of a five-year-old female with Down syndrome diagnosed with acute promyelocytic leukemia (APL). She came to our hospital with bleeding manifestations. Blood and bone marrow examination revealed promyelocytes showing a few fine granules and occasional Auer rods. Based on this morphology and cytochemistry, a diagnosis of APL microgranular variant (M3v) was made.</p> <p>Conclusion</p> <p>This case report emphasizes the importance of a high index of suspicion in the diagnosis of acute promyelocytic leukemia microgranular variant in Down syndrome.</p

Material-independent crack arrest statistics: Application to indentation experiments

An extensive experimental study of indentation and crack arrest statistics is presented for four different brittle materials (alumina, silicon carbide, silicon nitride, glass). Evidence is given that the crack length statistics can be described by a universal (i.e. material independent) distribution. The latter directly derives from results obtained when modeling crack propagation as a depinning phenomenon. Crack arrest (or effective toughness) statistics appears to be fully characterized by two parameters, namely, an asymptotic crack length (or macroscopic toughness) value and a power law size dependent width. The experimental knowledge of the crack arrest statistics at one given scale thus gives access to its knowledge at all scales

Higgs Oscillations in a Unitary Fermi Superfluid

Symmetry-breaking phase transitions are central to our understanding of states of matter. When a continuous symmetry is spontaneously broken, new excitations appear that are tied to fluctuations of the order parameter. In superconductors and fermionic superfluids, the phase and amplitude can fluctuate independently, giving rise to two distinct collective branches. However, amplitude fluctuations are difficult to both generate and measure, as they do not couple directly to the density of fermions and have only been observed indirectly to date. Here, we excite amplitude oscillations in an atomic Fermi gas with resonant interactions by an interaction quench. Exploiting the sensitivity of Bragg spectroscopy to the amplitude of the order parameter, we measure the time-resolved response of the atom cloud, directly revealing amplitude oscillations at twice the frequency of the gap. The magnitude of the oscillatory response shows a strong temperature dependence, and the oscillations appear to decay faster than predicted by time-dependent Bardeen-Cooper-Schrieffer theory applied to our experimental setup.</p

\u3cem\u3ePneumocystis\u3c/em\u3e Infection Alters the Activation State of Pulmonary Macrophages

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 days later. In co-infected animals, a higher proportion of macrophages in the alveolar and interstitial spaces expressed both classical and alternatively activated markers and produced the regulatory cytokines TGFβ and IL-10, as well as higher arginase levels than in mice infected with P. aeruginosa alone. Our results suggest that Pneumocystis reprograms the overall macrophage repertoire in the lung to that of a more alternatively-activated setpoint, thereby altering subsequent immune responses. These data may help to explain the association between Pneumocystis infection and decline in pulmonary function

In-beam internal conversion electron spectroscopy with the SPICE detector

The SPectrometer for Internal Conversion Electrons (SPICE) has been commissioned for use in conjunction with the TIGRESS $\gamma$-ray spectrometer at TRIUMF's ISAC-II facility. SPICE features a permanent rare-earth magnetic lens to collect and direct internal conversion electrons emitted from nuclear reactions to a thick, highly segmented, lithium-drifted silicon detector. This arrangement, combined with TIGRESS, enables in-beam $\gamma$-ray and internal conversion electron spectroscopy to be performed with stable and radioactive ion beams. Technical aspects of the device, capabilities, and initial performance are presented

Waveguide-integrated silicon T centres

The performance of modular, networked quantum technologies will be strongly dependent upon the quality of their quantum light-matter interconnects. Solid-state colour centres, and in particular T centres in silicon, offer competitive technological and commercial advantages as the basis for quantum networking technologies and distributed quantum computing. These newly rediscovered silicon defects offer direct telecommunications-band photonic emission, long-lived electron and nuclear spin qubits, and proven native integration into industry-standard, CMOS-compatible, silicon-on-insulator (SOI) photonic chips at scale. Here we demonstrate further levels of integration by characterizing T centre spin ensembles in single-mode waveguides in SOI. In addition to measuring long spin T_1 times, we report on the integrated centres' optical properties. We find that the narrow homogeneous linewidth of these waveguide-integrated emitters is already sufficiently low to predict the future success of remote spin-entangling protocols with only modest cavity Purcell enhancements. We show that further improvements may still be possible by measuring nearly lifetime-limited homogeneous linewidths in isotopically pure bulk crystals. In each case the measured linewidths are more than an order of magnitude lower than previously reported and further support the view that high-performance, large-scale distributed quantum technologies based upon T centres in silicon may be attainable in the near term

Neurology

Contains reports on eleven research projects.U.S. Air Force (AF49(638)-1130)Army Chemical Corps (DA-18-108-405-Cml-942)U.S. Public Health Service (B-3055)National Science Foundation (Grant G-16526)U.S. Public Health Service (B-3090)U.S. Air Force (AF33(616)-7588)Office of Naval Research (Nonr-1841(70)