Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies ...have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3beta (GSK-3beta), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.
Large peridotite massifs are scattered along the 1500km length of the Yarlung-Zangbo Suture Zone (southern Tibet, China), the major suture between Asia and Greater India. Diamonds occur in the ...peridotites and chromitites of several massifs, together with an extensive suite of trace phases that indicate extremely low fO sub(2) (SiC, nitrides, carbides, native elements) and/or ultrahigh pressures (UHP) (diamond, TiO sub(2) II, coesite, possible stishovite). New physical and isotopic (C, N) studies of the diamonds indicate that they are natural, crystallized in a disequilibrium, high-T environment, and spent only a short time at mantle temperatures before exhumation and cooling. These constraints are difficult to reconcile with previous models for the history of the diamond-bearing rocks. Possible evidence for metamorphism in or near the upper part of the Transition Zone includes the following: (1) chromite (in disseminated, nodular and massive chromitites) containing exsolved pyroxenes and coesite, suggesting inversion from a high-P polymorph of chromite; (2) microstructural studies suggesting that the chromitites recrystallized from fine-grained, highly deformed mixtures of wadsleyite and an octahedral polymorph of chromite; (3) a new cubic Mg-silicate, with the space group of ringwoodite but an inverse-spinel structure (all Si in octahedral coordination); (4) harzburgites with coarsely vermicular symplectites of opx + Cr-Al spinel plus or minus cpx; reconstructions suggest that these are the breakdown products of majoritic garnets, with estimated minimum pressures to>13GPa. Evidence for a shallow pre-metamorphic origin for the chromitites and peridotites includes the following: (1) trace-element data showing that the chromitites are typical of suprasubduction-zone (SSZ) chromitites formed by magma mixing or mingling, consistent with Hf-isotope data from magmatic (375Ma) zircons in the chromitites; (2) the composition of the new cubic Mg-silicate, which suggests a low-P origin as antigorite, subsequently dehydrated; (3) the peridotites themselves, which carry the trace element signature of metasomatism in an SSZ environment, a signature that must have been imposed before the incorporation of the UHP and low-fO sub(2) phases. A proposed P-T-t path involves the original formation of chromitites in mantle-wedge harzburgites, subduction of these harzburgites at c. 375Ma, residence in the upper Transition Zone for >200 Myr, and rapid exhumation at c. 170-150Ma or 130-120Ma. Os-isotope data suggest that the subducted mantle consisted of previously depleted subcontinental lithosphere, dragged down by a subducting oceanic slab. Thermomechanical modeling shows that roll-back of a (much later) subducting slab would produce a high-velocity channelized upwelling that could exhume the buoyant harzburgites (and their chromitites) from the Transition Zone in<10 Myr. This rapid upwelling, which may explain some characteristics of the diamonds, appears to have brought some massifs to the surface in forearc or back-arc basins, where they provided a basement for oceanic crust. This model can reconcile many apparently contradictory petrological and geological datasets. It also defines an important, previously unrecognized geodynamic process that may have operated along other large suture zones such as the Urals.
We demonstrate entangling quantum gates within a chain of five trapped ion qubits by optimally shaping optical fields that couple to multiple collective modes of motion. We individually address ...qubits with segmented optical pulses to construct multipartite entangled states in a programmable way. This approach enables high-fidelity gates that can be scaled to larger qubit registers for quantum computation and simulation.
Tau is the major microtubule associated protein (MAP) of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2. An established function of MAPs is their interaction with tubulin and ...promotion of its assembly into microtubules and stabilization of the microtubule network. The microtubule assembly promoting activity of tau, a phosphoprotein, is regulated by its degree of phosphorylation. Normal adult human brain tau contains 2-3 moles phosphate/mole of tau protein. Hyperphosphorylation of tau depresses this biological activity of tau. In Alzheimer disease (AD) brain tau is ~three to four-fold more hyperphosphorylated than the normal adult brain tau and in this hyperphosphorylated state it is polymerized into paired helical filaments (PHF) admixed with straight filaments (SF) forming neurofibrillary tangles. Tau is transiently hyperphosphorylated during development and during anesthesia and hypothermia but not to the same state as in AD brain. The abnormally hyperphosphorylated tau in AD brain is distinguished from transiently hyperphosphorylated tau by its ability (1) to sequester normal tau, MAP1 and MAP2 and disrupt microtubules, and (2) to self-assemble into PHF/SF. The cytosolic abnormally hyperphosphorylated tau, because of oligomerization, unlike normal tau, is sedimentable and on self-assembly into PHF/SF, loses its ability to sequester normal MAPs. Some of the tau in AD brain is truncated which also promotes its self-assembly. Tau mutations found in frontotemporal dementia apparently promote its abnormal hyperphosphorylation. Thus, the AD abnormally hyperphosphorylated tau (1) is distinguishable from both normal and transiently hyperphosphorylated taus, and (2) is inhibitory when in a cytosolic/oligomeric state but not when it is self-assembled into PHF/SF. Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.
Hybrid halide perovskites such as methylammonium lead iodide (CH3NH3PbI3) exhibit unusually low free‐carrier concentrations despite being processed at low‐temperatures from solution. We demonstrate, ...through quantum mechanical calculations, that an origin of this phenomenon is a prevalence of ionic over electronic disorder in stoichiometric materials. Schottky defect formation provides a mechanism to self‐regulate the concentration of charge carriers through ionic compensation of charged point defects. The equilibrium charged vacancy concentration is predicted to exceed 0.4 % at room temperature. This behavior, which goes against established defect conventions for inorganic semiconductors, has implications for photovoltaic performance.
Missing ion action: Schottky defects are found to be a dominant mode of equilibrium stoichiometric disorder in the photovoltaic material CH3NH3PbI3. This behavior can explain the previous finding that “the compounds show intense color, but there is no significant conductivity”.
We propose and analyze a new approach for quantum state transfer between remote spin qubits. Specifically, we demonstrate that coherent quantum coupling between remote qubits can be achieved via ...certain classes of random, unpolarized (infinite temperature) spin chains. Our method is robust to coupling-strength disorder and does not require manipulation or control over individual spins. In principle, it can be used to attain perfect state transfer over an arbitrarily long range via purely Hamiltonian evolution and may be particularly applicable in a solid-state quantum information processor. As an example, we demonstrate that it can be used to attain strong coherent coupling between nitrogen-vacancy centers separated by micrometer distances at room temperature. Realistic imperfections and decoherence effects are analyzed.
Two-dimensional (2D) semiconductors can be very useful for novel electronic and optoelectronic applications because of their good material properties. However, all current 2D materials have ...shortcomings that limit their performance. As a result, new 2D materials are highly desirable. Using atomic transmutation and differential evolution global optimization methods, we identified two group IV–VI 2D materials, Pma2-SiS and silicene sulfide. Pma2-SiS is found to be both chemically, energetically, and thermally stable. Most importantly, Pma2-SiS has shown good electronic and optoelectronic properties, including direct bandgaps suitable for solar cells, good mobility for nanoelectronics, good flexibility of property tuning by layer control and applied strain, and good air stability as well. Therefore, Pma2-SiS is expected to be a promising 2D material in the field of 2D electronics and optoelectronics. The designing principles demonstrated in identifying these two tantalizing examples have great potential to accelerate the finding of new functional 2D materials.
Laser-cooled and trapped atomic ions form an ideal standard for the simulation of interacting quantum spin models. Effective spins are represented by appropriate internal energy levels within each ...ion, and the spins can be measured with near-perfect efficiency using state-dependent fluorescence techniques. By applying optical fields that exert optical dipole forces on the ions, their Coulomb interaction can be modulated to produce long-range and tunable spin-spin interactions that can be reconfigured by shaping the spectrum and pattern of the laser fields in a prototypical example of a quantum simulator. Here the theoretical mapping of atomic ions to interacting spin systems, the preparation of complex equilibrium states, and the study of dynamical processes in these many-body interacting quantum systems are reviewed, and the use of this platform for optimization and other tasks is discussed. The use of such quantum simulators for studying spin models may inform our understanding of exotic quantum materials and shed light on the behavior of interacting quantum systems that cannot be modeled with conventional computers.
A consequent tendency toward high-performance quantum information processing is to develop the fully integrated photonic chip. Here, we report the on-chip generation and manipulation of entangled ...photons based on reconfigurable lithium-niobate waveguide circuits. By introducing a periodically poled structure into the waveguide circuits, two individual photon-pair sources with a controllable electro-optic phase shift are produced within a Hong-Ou-Mandel interferometer, resulting in a deterministically separated identical photon pair. The state is characterized by 92.9±0.9% visibility Hong-Ou-Mandel interference. The photon flux reaches ∼1.4×10(7) pairs nm-1 mW-1. The whole chip is designed to contain nine similar units to produce identical photon pairs spanning the telecom C and L band by the flexible engineering of nonlinearity. Our work presents a scenario for on-chip engineering of different photon sources and paves the way to fully integrated quantum technologies.
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