Dark Matter from Monogem

As a supernova shock expands into space, it may collide with dark matter particles, scattering them up to velocities more than an order of magnitude larger than typical dark matter velocities in the Milky Way. If a supernova remnant is close enough to Earth, and the appropriate age, this flux of high-velocity dark matter could be detectable in direct detection experiments, particularly if the dark matter interacts via a velocity-dependent operator. This could make it easier to detect light dark matter that would otherwise have too little energy to be detected. We show that the Monogem Ring supernova remnant is both close enough and the correct age to produce such a flux, and thus we produce novel direct detection constraints and sensitivities for future experiments.Comment: 8 Pages of Text, 3 Figure

Slowly cycling Rho kinase-dependent actomyosin cross-bridge slippage explains intrinsic high compliance of detrusor smooth muscle

Biological soft tissues are viscoelastic because they display timeindependent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+ -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as slipping cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically

Limnological Characteristics Reveal Metal Pollution Legacy in Lakes near Canada’s Northernmost Mine, Little Cornwallis Island, Nunavut

We compared modern limnological characteristics of three lakes near the world’s northernmost base metal (lead-zinc) mine, Polaris Mine, which operated from 1981 to 2002 on Little Cornwallis Island (Nunavut, Canada), to a suite of sites from Resolute Bay (Qausuittuq), Cornwallis Island. Although both study regions are underlain by broadly similar geology and experience nearly identical climatic conditions, present-day water chemistry variables differed markedly between sites on the two islands. Specifically, the lakes near the Polaris Mine recorded substantially higher concentrations of zinc and lead, as well as several other heavy metals (cadmium, molybdenum, nickel, uranium, vanadium), relative to the sites on Cornwallis Island. Although the Polaris Mine closed in 2002, elevated levels of heavy metals in our 2017 survey are likely a legacy of contamination from prior operations. Nous avons comparé les caractéristiques limnologiques modernes de trois lacs situés à proximité de la mine de métaux communs (plomb-zinc) la plus au nord du globe, soit la mine Polaris exploitée de 1981 à 2002 sur la Petite île Cornwallis (Nunavut, Canada), à une série de sites de la baie Resolute (Qausuittuq) sur l’île Cornwallis. Même si les deux régions à l’étude possèdent une géologie grandement similaire et qu’elles connaissent des conditions climatiques quasi identiques, les variables de la composition chimique de l’eau actuelle affichaient des différences considérables entre les sites des deux îles. Plus précisément, les lacs à proximité de la mine Polaris avaient des concentrations de plomb et de zinc nettement supérieures ainsi que plusieurs autres métaux lourds (cadmium, molybdène, nickel, uranium, vanadium) comparativement aux sites de l’île Cornwallis. Même si la mine Polaris a fermé ses portes en 2002, la présence de taux élevés de métaux lourds dans notre levé de 2017 découle vraisemblablement de la contamination émanant d’activités antérieures.&nbsp

New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity.

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA\u27s effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy

Effect of nanoparticle loading and magnetic field application on the thermodynamic, optical, and rheological behavior of thermoresponsive polymer solutions

Although processing via external stimuli is a promising technique to tune the structure and properties of polymeric materials, the impact of magnetic fields on phase transitions in thermoresponsive polymer solutions is not well-understood. As nanoparticle (NP) addition is also known to impact these thermodynamic and optical properties, synergistic effects from combining magnetic fields with NP incorporation provide a novel route for tuning material properties. Here, the thermodynamic, optical, and rheological properties of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions are examined in the presence of hydrophilic silica NPs and magnetic fields, individually and jointly, via Fourier-transform infrared spectroscopy (FTIR), magneto-turbidimetry, differential scanning calorimetry (DSC), and magneto-rheology. While NPs and magnetic fields both reduce the phase separation energy barrier and lower optical transition temperatures by altering hydrogen bonding (H-bonding), infrared spectra demonstrate that the mechanism by which these changes occur is distinct. Magnetic fields primarily alter solvent polarization while NPs provide PNIPAM–NP H-bonding sites. Combining NP addition with field application uniquely alters the solution environment and results in field-dependent rheological behavior that is unseen in polymer-only solutions. These investigations provide fundamental understanding on the interplay of magnetic fields and NP addition on PNIPAM thermoresponsivity which can be harnessed for increasingly complex stimuli-responsive materials

Detection of lensing substructure using ALMA observations of the dusty galaxy SDP.81

We study the abundance of substructure in the matter density near galaxies using ALMA Science Verification observations of the strong lensing system SDP.81. We present a method to measure the abundance of subhalos around galaxies using interferometric observations of gravitational lenses. Using simulated ALMA observations, we explore the effects of various systematics, including antenna phase errors and source priors, and show how such errors may be measured or marginalized. We apply our formalism to ALMA observations of SDP.81. We find evidence for the presence of a $M=10^{8.96\pm 0.12} M_{\odot}$ subhalo near one of the images, with a significance of $6.9\sigma$ in a joint fit to data from bands 6 and 7; the effect of the subhalo is also detected in both bands individually. We also derive constraints on the abundance of dark matter subhalos down to $M\sim 2\times 10^7 M_{\odot}$, pushing down to the mass regime of the smallest detected satellites in the Local Group, where there are significant discrepancies between the observed population of luminous galaxies and predicted dark matter subhalos. We find hints of additional substructure, warranting further study using the full SDP.81 dataset (including, for example, the spectroscopic imaging of the lensed carbon monoxide emission). We compare the results of this search to the predictions of $\Lambda$CDM halos, and find that given current uncertainties in the host halo properties of SDP.81, our measurements of substructure are consistent with theoretical expectations. Observations of larger samples of gravitational lenses with ALMA should be able to improve the constraints on the abundance of galactic substructure.Comment: 18 pages, 13 figures, Comments are welcom

Hypersonic Laminar Boundary Layer Velocimetry with Discrete Roughness on a Flat Plate

Laminar boundary layer velocity measurements are made on a 10-degree half-angle wedge in a Mach 10 flow. Two types of discrete boundary layer trips were used to perturb the boundary layer gas. The first was a 2-mm tall, 4-mm diameter cylindrical trip. The second was a scaled version of the Orbiter Boundary Layer Transition (BLT) Detailed Test Objective (DTO) trip. Both 1-mm and 2.5-mm tall BLT DTO trips were tested. Additionally, side-view and plan-view axial boundary layer velocity measurements were made in the absence of these tripping devices. The free-stream unit Reynolds numbers tested for the cylindrical trips were 1.7x10(exp 6)/m and 3.3x10(exp 6)/m. The free-stream unit Reynolds number tested for the BLT DTO trips was 1.7x10(exp 6)/m. The angle of attack was kept at approximately 5-degrees for most of the tests resulting in a Mach number of approximately 8.3. These combinations of unit Reynolds numbers and angle of attack resulted in laminar flowfields. To study the precision of the measurement technique, the angle of attack was varied during one run. Nitric-oxide (NO) molecular tagging velocimetry (MTV) was used to obtain averaged axial velocity values and associated uncertainties. These uncertainties are as low as 20 m/s. An interline, progressive scan CCD camera was used to obtain separate images of the initial reference and shifted NO molecules that had been tagged by the laser. The CCD configuration allowed for sub-microsecond sequential acquisition of both images. The maximum planar spatial resolution achieved for the side-view velocity measurements was 0.07-mm in the wall-normal direction by 1.45-mm in the streamwise direction with a spatial depth of 0.5-mm. For the plan-view measurements, the maximum planar spatial resolution in the spanwise and streamwise directions was 0.69-mm by 1.28-mm, respectively, with a spatial depth of 0.5-mm. Temperature sensitive paint (TSP) measurements are provided to compliment the velocity data and to provide further insight into the behavior of the boundary layers. The experiments were performed at the NASA Langley Research Center 31-Inch Mach 10 Air tunnel

Microbial Co-Infection Alters Macrophage Polarization, Phagosomal Escape, and Microbial Killing

Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection. Non-activated (M0) macrophages or activated M2-polarized cells (J774 cells transfected with the mouse IL-4 gene) were first infected with BCG for 24–48 h, subsequently challenged with LVS, and the results of inhibition of LVS replication in the macrophages was assessed. BCG infection in M0 macrophages activated TLR2-MyD88 and Mincle-CARD9 signaling pathways, stimulating nitric oxide (NO) production and enhanced killing of LVS. BCG infection had little effect on LVS escape from phagosomes into the cytosol in M0 macrophages. In contrast, M2-polarized macrophages exhibited enhanced endosomal acidification, as well as inhibiting LVS replication. Pre-infection with BCG did not induce NO production and thus did not further reduce LVS replication. This study provides a model for studies of the complexity of macrophage activation in response to multi-bacterial infection

Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH) and fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI), differ with aging and cerebrovascular disease (CVD) and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals