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Featured researches published by S.A. Cohen.


Nature Structural & Molecular Biology | 2015

A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers.

S.A. Cohen; Paolo Arosio; Jenny Presto; Firoz Roshan Kurudenkandy; Henrik Biverstål; Lisa Dolfe; Christopher J.R. Dunning; Xiaoting Yang; Birgitta Frohm; Michele Vendruscolo; Jan Johansson; Christopher M. Dobson; André Fisahn; Tuomas P. J. Knowles; Sara Linse

Alzheimers disease is an increasingly prevalent neurodegenerative disorder whose pathogenesis has been associated with aggregation of the amyloid-β peptide (Aβ42). Recent studies have revealed that once Aβ42 fibrils are generated, their surfaces effectively catalyze the formation of neurotoxic oligomers. Here we show that a molecular chaperone, a human Brichos domain, can specifically inhibit this catalytic cycle and limit human Aβ42 toxicity. We demonstrate in vitro that Brichos achieves this inhibition by binding to the surfaces of fibrils, thereby redirecting the aggregation reaction to a pathway that involves minimal formation of toxic oligomeric intermediates. We verify that this mechanism occurs in living mouse brain tissue by cytotoxicity and electrophysiology experiments. These results reveal that molecular chaperones can help maintain protein homeostasis by selectively suppressing critical microscopic steps within the complex reaction pathways responsible for the toxic effects of protein misfolding and aggregation.


Physics of Plasmas | 2003

Ion Acceleration in Plasmas Emerging from a Helicon-heated Magnetic-mirror Device

S.A. Cohen; N. S. Siefert; S. Stange; Robert F. Boivin; Earl Scime; F. M. Levinton

Using laser-induced fluorescence, measurements have been made of metastable argon-ion, Ar+*(3d4F7/2), velocity distributions on the major axis of an axisymmetric magnetic-mirror device whose plasma is sustained by helicon wave absorption. Within the mirror, these ions have sub-eV temperature and, at most, a subthermal axial drift. In the region outside the mirror coils, conditions are found where these ions have a field-parallel velocity above the acoustic speed, to an axial energy of ∼30 eV, while the field-parallel ion temperature remains low. The supersonic Ar+*(3d4F7/2) are accelerated to one-third of their final energy within a short region in the plasma column, ⩽1 cm, and continue to accelerate over the next 5 cm. Neutral-gas density strongly affects the supersonic Ar+*(3d4F7/2) density.


Journal of Nuclear Materials | 1979

A model for hydrogen isotope backscattering, trapping and depth profiles in carbon and amorphous silicon

S.A. Cohen; G.M. McCracken

Abstract A model for low-energy hydrogen trapping and backscattering in carbon and amorphous silicon is described. Depth profiles are calculated and numerical results presented for various incident angular and energy distributions. The calculations yield a relation between depth profiles and the incident-ion energy distribution. The results obtained for reflection coefficients and for saturation doses are in good agreement with those obtained experimentally as described in the companion paper. The use of the model for tokamak plasma diagnosis is discussed.


Journal of Nuclear Materials | 1978

Long-term changes in the surface conditions of PLT

S.A. Cohen; H.F. Dylla; S.M. Rossnagel; S.T. Picraux; J.A. Borders; C.W. Magee

Long-term changes in the surface conditions of the PLT vacuum vessel wall have been monitored by the periodic analysis of a variety of sample substrates (stainless steel, alumina, silicon), exposed to PLT discharges for periods of up to several months and subsequently removed for analysis by Auger electron spectroscopy (AES), photoelectron spectroscopy (ESCA), ion backscattering, nuclear reaction analysis, secondary ion mass spectrometry (SIMS), and scanning electron microscopy. Samples exposed for extended time periods (2–6 months) showed deposited films containing limiter (W) and liner constituent metals (Fe, Cr, and Ni) and C and O. The film thicknesses ranged between 100 and 200 A with 2–15 at.% W and 5–40% Fe as determined by sputter-AES and ion backscattering measurements. Increased deposition of metallic impurities (W, Fe) was noted following the first extensive application of low power discharge cleaning. We discuss the possible mechanisms responsible for the deposition of metals onto the sample surfaces. Deuterium retention was observed in all the exposed samples with the deuterium depth profiles restricted primarily to the deposited films on the stainless steel substrates and extending deeper for Si. The retained deuterium measured in the exposed samples shows a saturation in the retention of (1–11) × 1015Datoms/cm2 for an estimated variation in the deuterium fluence of 1016–1018 D atoms/cm2.


Journal of Nuclear Materials | 1978

Tokamak plasma diagnosis by surface physics techniques

S.A. Cohen

The utilization of elementally-sensitive surface techniques as plasma diagnostics is discussed with emphasis on measuring impurity fluxes, charge states, and energy distributions in the plasma edge. A model of plasma flow to the probe is presented and applied to the interpretation of data. Limits on time and energy resolution, and sensitivity are given. The overlap of these techniques with conventional plasma diagnostics is described.


Nuclear Fusion | 1981

Mechanisms responsible for topographical changes in PLT stainless-steel and graphite limiters

S.A. Cohen; Robert V. Budny; G.M. McCracken; M. Ulrickson

PLT limiters used during Ohmic and neutral-beam heated discharges were melted and eroded. For the steel limiters, the pattern of large (20 cm2) melted areas was 0.1–1.0-mm ripples in a regular array. The various types of damage can be explained by the power and momentum fluxes of bulk plasma and beam ions and by disruptions. The plasma scrape-off distance inferred from the extent of the damage ranges from 5 to 30 mm and is consistent with a radially outward drift velocity of 2 × 104 mms−1. A new model of the plasma scrape-off is presented which explains pattern and extent of the damage.


Journal of Nuclear Materials | 1987

Plasma-material interactions in TFTR

H.F. Dylla; Team Tftr Team; M.G. Bell; W. Blanchard; P. P. Boody; N. Bretz; R.V. Budny; C.E. Bush; Joseph L. Cecchi; S.A. Cohen; S. K. Combs; S. Davis; B.L. Doyle; P.C. Efthimion; A. C. England; H.P. Eubank; R.J. Fonck; E. D. Fredrickson; L R Grisham; R.J. Goldston; B. Grek; R. Groebner; R.J. Hawryluk; D.B. Heifetz; H. W. Hendel; K. W. Hill; S. Hiroe; R. Hulse; D. Johnson; L. C. Johnson

This paper presents a summary of plasma-material interactions which influence the operation of TFTR with high current (≤ 2.2 MA) ohmically heated, and high-power (∼ 10 MW) neutral-beam heated plasmas. The conditioning procedures which are applied routinely to the first-wall hardware are reviewed. Fueling characteristics during gas, pellet, and neutral-beam fueling are described. Recycling coefficients near unity are observed for most gas fueled discharges. Gas fueled discharges after helium discharge conditioning of the toroidal bumper limiter, and discharges fueled by neutral beams and pellets, show R<1. In the vicinity of the gas fueled density limit (at ne = 5–6 × 1019 m−3) values of Zeff are ≦1.5. Increases in Zeff of ≦1 have been observed with neutral beam heating of 10 MW. The primary low Z impurity is carbon with concentrations decreasing from ∼10% to <1% with increasing ne. Oxygen densities tend to increase with ne, and at the ohmic plasma density limit oxygen and carbon concentrations are comparable. Chromium getter experiments and He2+/D+ plasma comparisons indicate that the limiter is the primary source of carbon and that the vessel wall is a significant source of the oxygen impurity. Metallic impurities, consisting of the vacuum vessel metals (Ni, Fe, Cr) have significant (∼10−4 ne) concentrations only at low plasma densities (ne <1019 m−3). The primary source of metallic impurities is most likely ion sputtering from metals deposited on the carbon limiter surface.


Nuclear Instruments and Methods | 1980

Depth distributions of low energy deuterium implanted into silicon as determined by SIMS

Charles W. Magee; S.A. Cohen; Donald E. Voss; D.K. Brice

Secondary ion mass spectrometry (SIMS) has been used to determine depth profiles of deuterium implanted into single crystal silicon targets at energies between 0.1 and 5 keV. The atomic mixing inherent in the sputtering process, which directly affects depth resolution, has been reduced by using a bombarding particle of low energy and high Z impacting the sample at a large angle relative to the surface normal (3 keV, Cs/sup +/, impacting at 60/sup 0/). Using this procedure, depth resolution of 20 A at a depth of 800 A has been obtained in depth profiling of Ta/sub 2/O/sub 5/ on Ta. Mean projected range and straggling of the implant profiles are in good agreement with calculations when irradiations are performed at 11/sup 0/ from the normal to the (100) plane to prevent channeling. The saturation density of trapped deuterium has also been determined to be 1.4 x 10/sup 22/ D/cm/sup 3/.


Physics of Plasmas | 2000

Maintaining the closed magnetic-field-line topology of a field-reversed configuration with the addition of static transverse magnetic fields

S.A. Cohen; Richard D. Milroy

The effects on magnetic-field-line structure of adding various static transverse magnetic fields to a Solov’ev-equilibrium field-reversed configuration are examined. It is shown that adding fields that are antisymmetric about the axial midplane maintains the closed field-line structure, while adding fields with planar or helical symmetry opens the field structure. Antisymmetric modes also introduce pronounced shear.


Applied Physics Letters | 1997

A source of hyperthermal neutrals for materials processing

Matthew Goeckner; T.K. Bennett; S.A. Cohen

In this letter, we describe a unique method of producing hyperthermal neutrals for material processing. The hyperthermal neutrals are produced by accelerating ions across a sheath from a plasma onto a surface. On impact, the ions are neutralized and reflected with ∼50% of their incident energy. These neutrals then bounce off of additional surfaces prior to impacting the target. This unique multiple bounce system was developed for the following reasons: to reduce contamination from sputtered surface material, improve beam uniformity, and reduce UV radiation in the beam path. As a test of this method, we built a prototype beam source and used it to ash photoresist at rates up to 0.022 μm/min. These rates are consistent with a predicted neutral beam flux, 2×1014 cm−2 s−1. In addition, a simple model is used to indicate that this method is capable of producing economically acceptable ash rates. Comparisons with other neutral-beam production methods are made.

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D. Manos

Princeton University

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N. Bretz

Princeton University

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R. V. Budny

Princeton Plasma Physics Laboratory

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