Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson’s disease and Multiple System Atrophy

Aggregated alpha-synuclein (a-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of a-synuclein exist, including phosphorylated and nitrated forms. It is unclear which a-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant a-synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three a-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology- affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 a-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 a- synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 a- synuclein in MSA. Quantification of the LB scores revealed that pS129 a-synuclein was the dominant and earliest a-synuclein PTM followed by nY39 a-synuclein, while lower amounts of pSer87 a-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments

Journal Staff

A time-dependent coordinate transformation of a constant coeffcient hyperbolic equation which results in a variable coeffcient problem is considered. By using the energy method, we derive well-posed boundary conditions for the continuous problem. It is shown that the number of boundary conditions depend on the coordinate transformation. By using Summation-by-Parts (SBP) operators for the space discretization and weak boundary conditions, an energy stable finite dieffrence scheme is obtained. We also show how to construct a time-dependent penalty formulation that automatically imposes the right number of boundary conditions. Numerical calculations corroborate the stability and accuracy of the approximations

The Initial Mass Function of Low-Mass Stars and Brown Dwarfs in Young Clusters

We have obtained images of the Trapezium Cluster (140" x 140"; 0.3 pc x 0.3 pc) with the Hubble Space Telescope Near-Infrared Camera and Multi-Object Spectrometer (NICMOS). Combining these data with new ground-based K-band spectra (R=800) and existing spectral types and photometry and the models of D'Antona & Mazzitelli, we find that the distributions of ages of comparable samples of stars in the Trapezium, rho Oph, and IC 348 indicate median ages of \~0.4 Myr for the first two regions and ~1-2 Myr for the latter. The low-mass IMFs in these sites of clustered star formation are similar over a wide range of stellar densities and other environmental conditions. With current data, we cannot rule out modest variations in the substellar mass functions among these clusters. We then make the best estimate of the true form of the IMF in the Trapezium by using the evolutionary models of Baraffe et al. and an empirically adjusted temperature scale and compare this mass function to recent results for the Pleiades and the field. All of these data are consistent with an IMF that is flat or rises slowly from the substellar regime to about 0.6 Msun, and then rolls over into a power law that continues from about 1 Msun to higher masses with a slope similar to or somewhat larger than the Salpeter value of 1.35. For the Trapezium, this behavior holds from our completeness limit of ~0.02 Msun and probably, after a modest completeness correction, even from 0.01-0.02 Msun. These data include ~50 likely brown dwarfs. We test the predictions of theories of the IMF against various properties of the observed IMF.Comment: 34 pages, 13 figures, for color image see http://cfa-www.harvard.edu/~kluhman/trap/colorimage.jp

On free evolution of self gravitating, spherically symmetric waves

We perform a numerical free evolution of a selfgravitating, spherically symmetric scalar field satisfying the wave equation. The evolution equations can be written in a very simple form and are symmetric hyperbolic in Eddington-Finkelstein coordinates. The simplicity of the system allow to display and deal with the typical gauge instability present in these coordinates. The numerical evolution is performed with a standard method of lines fourth order in space and time. The time algorithm is Runge-Kutta while the space discrete derivative is symmetric (non-dissipative). The constraints are preserved under evolution (within numerical errors) and we are able to reproduce several known results.Comment: 15 pages, 15 figure

"Open Innovation" and "Triple Helix" Models of Innovation: Can Synergy in Innovation Systems Be Measured?

The model of "Open Innovations" (OI) can be compared with the "Triple Helix of University-Industry-Government Relations" (TH) as attempts to find surplus value in bringing industrial innovation closer to public R&D. Whereas the firm is central in the model of OI, the TH adds multi-centeredness: in addition to firms, universities and (e.g., regional) governments can take leading roles in innovation eco-systems. In addition to the (transversal) technology transfer at each moment of time, one can focus on the dynamics in the feedback loops. Under specifiable conditions, feedback loops can be turned into feedforward ones that drive innovation eco-systems towards self-organization and the auto-catalytic generation of new options. The generation of options can be more important than historical realizations ("best practices") for the longer-term viability of knowledge-based innovation systems. A system without sufficient options, for example, is locked-in. The generation of redundancy -- the Triple Helix indicator -- can be used as a measure of unrealized but technologically feasible options given a historical configuration. Different coordination mechanisms (markets, policies, knowledge) provide different perspectives on the same information and thus generate redundancy. Increased redundancy not only stimulates innovation in an eco-system by reducing the prevailing uncertainty; it also enhances the synergy in and innovativeness of an innovation system.Comment: Journal of Open Innovations: Technology, Market and Complexity, 2(1) (2016) 1-12; doi:10.1186/s40852-016-0039-

Low-Temperature Growth of Graphene on a Semiconductor

The industrial realization of graphene has so far been limited by challenges related to the quality, reproducibility, and high process temperatures required to manufacture graphene on suitable substrates. We demonstrate that epitaxial graphene can be grown on transition-metal-treated 6H-SiC(0001) surfaces, with an onset of graphitization starting around 450–500 °C. From the chemical reaction between SiC and thin films of Fe or Ru, sp3 carbon is liberated from the SiC crystal and converted to sp2 carbon at the surface. The quality of the graphene is demonstrated by using angle-resolved photoemission spectroscopy and low-energy electron diffraction. Furthermore, the orientation and placement of the graphene layers relative to the SiC substrate are verified by using angle-resolved absorption spectroscopy and energy-dependent photoelectron spectroscopy, respectively. With subsequent thermal treatments to higher temperatures, a steerable diffusion of the metal layers into the bulk SiC is achieved. The result is graphene supported on magnetic silicide or optionally, directly on semiconductor, at temperatures ideal for further large-scale processing into graphene-based device structures

The influence of anthropogenic aerosol on multi-decadal variations of historical global climate

Analysis of single forcing runs from CMIP5 (the fifth Coupled Model Intercomparison Project) simulations shows that the mid-twentieth century temperature hiatus, and the coincident decrease in precipitation, is likely to have been influenced strongly by anthropogenic aerosol forcing. Models that include a representation of the indirect effect of aerosol better reproduce inter-decadal variability in historical global-mean near-surface temperatures, particularly the cooling in the 1950s and 1960s, compared to models with representation of the aerosol direct effect only. Models with the indirect effect also show a more pronounced decrease in precipitation during this period, which is in better agreement with observations, and greater inter-decadal variability in the inter-hemispheric temperature difference. This study demonstrates the importance of representing aerosols, and their indirect effects, in general circulation models, and suggests that inter-model diversity in aerosol burden and representation of aerosol–cloud interaction can produce substantial variation in simulations of climate variability on multi decadal timescales

Optical properties of LaNiO3 films tuned from compressive to tensile strain

Materials with strong electronic correlations host remarkable -- and technologically relevant -- phenomena such as magnetism, superconductivity and metal-insulator transitions. Harnessing and controlling these effects is a major challenge, on which key advances are being made through lattice and strain engineering in thin films and heterostructures, leveraging the complex interplay between electronic and structural degrees of freedom. Here we show that the electronic structure of LaNiO3 can be tuned by means of lattice engineering. We use different substrates to induce compressive and tensile biaxial epitaxial strain in LaNiO3 thin films. Our measurements reveal systematic changes of the optical spectrum as a function of strain and, notably, an increase of the low-frequency free carrier weight as tensile strain is applied. Using density functional theory (DFT) calculations, we show that this apparently counter-intuitive effect is due to a change of orientation of the oxygen octahedra.The calculations also reveal drastic changes of the electronic structure under strain, associated with a Fermi surface Lifshitz transition. We provide an online applet to explore these effects. The experimental value of integrated spectral weight below 2 eV is significantly (up to a factor of 3) smaller than the DFT results, indicating a transfer of spectral weight from the infrared to energies above 2 eV. The suppression of the free carrier weight and the transfer of spectral weight to high energies together indicate a correlation-induced band narrowing and free carrier mass enhancement due to electronic correlations. Our findings provide a promising avenue for the tuning and control of quantum materials employing lattice engineering.Comment: 12 pages, 11 figure