A switch element in the autophagy E2 Atg3 mediates allosteric regulation across the lipidation cascade

Autophagy depends on the E2 enzyme, Atg3, functioning in a conserved E1-E2-E3 trienzyme cascade that catalyzes lipidation of Atg8-family ubiquitin-like proteins (UBLs). Molecular mechanisms underlying Atg8 lipidation remain poorly understood despite association of Atg3, the E1 Atg7, and the composite E3 Atg12-Atg5-Atg16 with pathologies including cancers, infections and neurodegeneration. Here, studying yeast enzymes, we report that an Atg3 element we term E123IR (E1, E2, and E3-interacting region) is an allosteric switch. NMR, biochemical, crystallographic and genetic data collectively indicate that in the absence of the enzymatic cascade, the Atg3(E123IR) makes intramolecular interactions restraining Atg3's catalytic loop, while E1 and E3 enzymes directly remove this brace to conformationally activate Atg3 and elicit Atg8 lipidation in vitro and in vivo. We propose that Atg3's E123IR protects the E2 similar to UBL thioester bond from wayward reactivity toward errant nucleophiles, while Atg8 lipidation cascade enzymes induce E2 active site remodeling through an unprecedented mechanism to drive autophagy

Superconductivity of the Ternary Boride Li_2Pd_3B Probed by ^{11}B NMR

We report a ^{11}B NMR measurement on the recently discovered superconductor Li_2Pd_3B. The nuclear spin lattice relaxation rate 1/T_1 shows a well-defined coherence peak just below T_c (H=1.46 T)=5.7 K, and the spin susceptibility measured by the Knight shift also decreases below T_c. These results indicate that the superconductivity is of conventional nature, with an isotropic gap. Our results also suggest that the $p$-electrons of boron and the d-electrons of palladium that hybridize with boron $p$-electrons are primarily responsible for the superconductivity.Comment: 4 pages, 5 figure

Model estimation of cerebral hemodynamics between blood flow and volume changes: a data-based modeling approach

It is well known that there is a dynamic relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV). With increasing applications of functional MRI, where the blood oxygen-level-dependent signals are recorded, the understanding and accurate modeling of the hemodynamic relationship between CBF and CBV becomes increasingly important. This study presents an empirical and data-based modeling framework for model identification from CBF and CBV experimental data. It is shown that the relationship between the changes in CBF and CBV can be described using a parsimonious autoregressive with exogenous input model structure. It is observed that neither the ordinary least-squares (LS) method nor the classical total least-squares (TLS) method can produce accurate estimates from the original noisy CBF and CBV data. A regularized total least-squares (RTLS) method is thus introduced and extended to solve such an error-in-the-variables problem. Quantitative results show that the RTLS method works very well on the noisy CBF and CBV data. Finally, a combination of RTLS with a filtering method can lead to a parsimonious but very effective model that can characterize the relationship between the changes in CBF and CBV

Quantum computing through electron propagation in the edge states of quantum spin Hall systems

We propose to implement quantum computing based on electronic spin qubits by controlling the propagation of the electron wave packets through the helical edge states of quantum spin Hall systems (QSHs). Specfically, two non-commutative single-qubit gates, which rotate a qubit around z and y axes, can be realized by utilizing gate voltages either on a single QSH edge channel or on a quantum point contact structure. The more challenging two-qubit controlled phase gate can be implemented through the on-demand capacitive Coulomb interaction between two adjacent edge channels from two parallel QSHs. As a result, a universal set of quantum gates can be achieved in an all-electrical way. The fidelity and purity of the two-qubit gate are calculated with both time delay and finite width of the wave packets taken into consideration, which can reach high values with the existing high-quality single electron source

Understanding the Economic Consequences of Shifting Trends in Population Health

The public economic burden of shifting trends in population health remains uncertain. Sustained increases in obesity, diabetes, and other diseases could reduce life expectancy – with a concomitant decrease in the public-sector’s annuity burden – but these savings may be offset by worsening functional status, which increases health care spending, reduces labor supply, and increases public assistance. Using a microsimulation approach, we quantify the competing public-finance consequences of shifting trends in population health for medical care costs, labor supply, earnings, wealth, tax revenues, and government expenditures (including Social Security and income assistance). Together, the reduction in smoking and the rise in obesity have increased net public-sector liabilities by $430bn, or approximately 4% of the current debt burden. Larger effects are observed for specific public programs: annual spending is 10% higher in the Medicaid program, and 7% higher for Medicare.disability, health care costs, social security, microsimulation

International Differences in Longevity and Health and their Economic Consequences

In 1975, 50 year-old Americans could expect to live slightly longer than their European counterparts. By 2005, American life expectancy at that age has diverged substantially compared to Europe. We find that this growing longevity gap is primarily the symptom of real declines in the health of near-elderly Americans, relative to their European peers. In particular, we use a microsimulation approach to project what US longevity would look like, if US health trends approximated those in Europe. We find that differences in health can explain most of the growing gap in remaining life expectancy. In addition, we quantify the public finance consequences of this deterioration in health. The model predicts that gradually moving American cohorts to the health status enjoyed by Europeans could save up to $1.1 trillion in discounted total health expenditures from 2004 to 2050.disability, mortality, international comparisons, microsimulation

Real-time diffuse optical tomography using reduced-order light propagation models based on a priori anatomical and functional information

This paper proposes a new fast 3D image reconstruction algorithm for Diffuse Optical Tomography using reduced order polynomial mappings from the space of optical tissue parameters into the space of flux measurements at the detector locations. The polynomial mappings are constructed through an iterative estimation process involving structure detection, parameter estimation and cross-validation using data generated by simulating a diffusion approximation of the radiative transfer equation incorporating a priori anatomical and functional information provided by MR scans and prior psychological evidence. Numerical simulation studies demonstrate that reconstructed images are remarkably similar in quality as those obtained using the standard approach, but obtained at a fraction of the time