Does Global Health Funding Respond to Recipients’ Needs? Comparing Public and Private Donors’ Allocations in 2005–2007

Adding to official development assistance (ODA), private foundations have emerged as important donors to the global health agenda. Amid this increasing funder diversity and growing global health budgets, responsiveness to recipients’ needs is a central concern. Merging datasets on ODA flows in 2005–07, over 2,800 foundation grants, disease burden, and perceived priorities in 27 low- and middle-income countries, this study offers the first comprehensive national-level analysis of global health aid responsiveness. The analysis shows that national patterns of disease burden explain neither public nor private aid flows during this period. While ODA committed during these years was weakly yet significantly correlated with health priorities, private grants’ responsiveness was even weaker and did not achieve ODA significance levels either

Unrestrained cleavage of Roquin-1 by MALT1 induces spontaneous T cell activation and the development of autoimmunity

Constitutive activation of the MALT1 paracaspase in conventional T cells of Malt1TBM/TBM (TRAF6 Binding Mutant = TBM) mice causes fatal inflammation and autoimmunity, but the involved targets and underlying molecular mechanisms are unknown. We genet-ically rendered a single MALT1 substrate, the RNA- binding protein (RBP) Roquin-1, insensitive to MALT1 cleavage. These Rc3h1Mins/Mins mice showed normal immune homeostasis. Combining Rc3h1Mins/Mins alleles with those encoding for constitutively active MALT1 (TBM) prevented spontaneous T cell activation and restored viability of Malt1TBM/TBM mice. Mechanistically, we show how antigen/MHC recognition is trans-lated by MALT1 into Roquin cleavage and derepression of Roquin targets. Increasing T cell receptor (TCR) signals inactivated Roquin more effectively, and only high TCR strength enabled derepression of high- affinity targets to promote Th17 differentiation. Induction of experimental autoimmune encephalomyelitis (EAE) revealed increased cleavage of Roquin-1 in disease- associated Th17 compared to Th1 cells in the CNS. T cells from Rc3h1Mins/Mins mice did not efficiently induce the high- affinity Roquin-1 target I kappa BNS in response to TCR stimulation, showed reduced Th17 differentiation, and Rc3h1Mins/Mins mice were protected from EAE. These data demonstrate how TCR signaling and MALT1 activation utilize graded cleavage of Roquin to differentially regulate target mRNAs that control T cell activation and differentiation as well as the development of autoimmunity

The three-dimensional random field Ising magnet: interfaces, scaling, and the nature of states

The nature of the zero temperature ordering transition in the 3D Gaussian random field Ising magnet is studied numerically, aided by scaling analyses. In the ferromagnetic phase the scaling of the roughness of the domain walls, $w\sim L^\zeta$, is consistent with the theoretical prediction $\zeta = 2/3$. As the randomness is increased through the transition, the probability distribution of the interfacial tension of domain walls scales as for a single second order transition. At the critical point, the fractal dimensions of domain walls and the fractal dimension of the outer surface of spin clusters are investigated: there are at least two distinct physically important fractal dimensions. These dimensions are argued to be related to combinations of the energy scaling exponent, $\theta$, which determines the violation of hyperscaling, the correlation length exponent $\nu$, and the magnetization exponent $\beta$. The value $\beta = 0.017\pm 0.005$ is derived from the magnetization: this estimate is supported by the study of the spin cluster size distribution at criticality. The variation of configurations in the interior of a sample with boundary conditions is consistent with the hypothesis that there is a single transition separating the disordered phase with one ground state from the ordered phase with two ground states. The array of results are shown to be consistent with a scaling picture and a geometric description of the influence of boundary conditions on the spins. The details of the algorithm used and its implementation are also described.Comment: 32 pp., 2 columns, 32 figure

First Results from HaloSat – A CubeSat to Study the Hot Galactic Halo

HaloSat is the first CubeSat for astrophysics funded by NASA\u27s Science Mission Directorate and is designed to map soft X-ray oxygen line emission across the sky in order to constrain the mass and spatial distribution of hot gas in the Milky Way. HaloSat will help determine if hot halos with temperatures near a million degrees bound to galaxies make a significant contribution to the cosmological budget of the normal matter (baryons). HaloSat was deployed from the International Space Station in July 2018 and began routine science operations in October 2018. We describe the on-orbit performance including calibration of the X-ray detectors and initial scientific results including an observation of a halo field and an observation of solar wind charge exchange emission from the helium-focusing cone

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Effective Reduced Diffusion-Models: A Data Driven Approach to the Analysis of Neuronal Dynamics

We introduce in this paper a new method for reducing neurodynamical data to an effective diffusion equation, either experimentally or using simulations of biophysically detailed models. The dimensionality of the data is first reduced to the first principal component, and then fitted by the stationary solution of a mean-field-like one-dimensional Langevin equation, which describes the motion of a Brownian particle in a potential. The advantage of such description is that the stationary probability density of the dynamical variable can be easily derived. We applied this method to the analysis of cortical network dynamics during up and down states in an anesthetized animal. During deep anesthesia, intracellularly recorded up and down states transitions occurred with high regularity and could not be adequately described by a one-dimensional diffusion equation. Under lighter anesthesia, however, the distributions of the times spent in the up and down states were better fitted by such a model, suggesting a role for noise in determining the time spent in a particular state

Endomembrane targeting of human OAS1 p46 augments antiviral activity

Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flaviviruses, picornaviruses, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform correlates with protection from severe COVID-19. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests that early control of SARS-CoV-2 replication through OAS1 p46 is an important determinant of COVID-19 severity

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented