2,104 research outputs found
Characterizing heterogeneous dynamics at hydrated electrode surfaces
In models of Pt 111 and Pt 100 surfaces in water, motions of molecules in the
first hydration layer are spatially and temporally correlated. To interpret
these collective motions, we apply quantitative measures of dynamic
heterogeneity that are standard tools for considering glassy systems.
Specifically, we carry out an analysis in terms of mobility fields and
distributions of persistence times and exchange times. In so doing, we show
that dynamics in these systems is facilitated by transient disorder in
frustrated two-dimensional hydrogen bonding networks. The frustration is the
result of unfavorable geometry imposed by strong metal-water bonding. The
geometry depends upon the structure of the underlying metal surface. Dynamic
heterogeneity of water on the Pt 111 surface is therefore qualitatively
different than that for water on the Pt 100 surface. In both cases, statistics
of this adlayer dynamic heterogeneity responds asymmetrically to applied
voltage.Comment: 6 page, 4 figure
Solvation at Aqueous Metal Electrodes
We present a study of the solvation properties of model aqueous electrode
interfaces. The exposed electrodes we study strongly bind water and have closed
packed crystalline surfaces, which template an ordered water adlayer adjacent
to the interface. We find that these ordered water structures facilitate
collective responses in the presence of solutes that are correlated over large
lengthscales and across long timescales. Specifically, we show that the liquid
water adjacent to the ordered adlayers forms a soft, liquid-vapor-like
interface with concomitant manifestations of hydrophobicity. Temporal defects
in the adlayer configurations create a dynamic heterogeneity in the degree to
which different regions of the interface attract hydrophobic species. The
structure and heterogeneous dynamics of the adlayer defects depend upon the
geometry of the underlying ordered metal surface. For both 100 and 111
surfaces, the dynamical heterogeneity relaxes on times longer than nanoseconds.
Along with analyzing time scales associated with these effects, we highlight
implications for electrolysis and the particular catalytic efficiency of
platinum.Comment: 9 pages, 8 figure
Charge fluctuations in nano-scale capacitors
The fluctuations of the charge on an electrode contain information on the
microscopic correlations within the adjacent fluid and their effect on the
electronic properties of the interface. We investigate these fluctuations using
molecular dynamics simulations in a constant-potential ensemble with histogram
reweighting techniques. This approach offers in particular an efficient,
accurate and physically insightful route to the differential capacitance that
is broadly applicable. We demonstrate these methods with three different
capacitors: pure water between platinum electrodes, and a pure as well as a
solvent-based organic electrolyte each between graphite electrodes. The total
charge distributions with the pure solvent and solvent-based electrolytes are
remarkably Gaussian, while in the pure ionic liquid the total charge
distribution displays distinct non-Gaussian features, suggesting significant
potential-driven changes in the organization of the interfacial fluid
Catalyzing Social Innovation: Leveraging Compassion and Open Strategy in Social Entrepreneurship
We implement an inductive, case study approach to explore the motivations and methods of five successful social entrepreneurs. Our findings show that founders noticed, felt, and responded to someone elseâs pain, demonstrating compassion as the genesis of the business venture. Successful social innovation, however, was the result of the creation of an organization structured to include diverse stakeholder input and participation in the decision-making process. Thus, compassion motivates entrepreneurs to pursue broad gains as opposed to singular interests and enhances a willingness to incorporate othersâ ideas through an open-strategy process. Our study suggests that interaction with stakeholders can impact the structure of the firm, the business model it employs, and intended and unintended business consequences
Water exchange at a hydrated platinum electrode is rare and collective
We use molecular dynamics simulations to study the exchange kinetics of water
molecules at a model metal electrode surface -- exchange between water
molecules in the bulk liquid and water molecules bound to the metal. This
process is a rare event, with a mean residence time of a bound water of about
40 ns for the model we consider. With analysis borrowed from the techniques of
rare-event sampling, we show how this exchange or desorption is controlled by
(1) reorganization of the hydrogen bond network within the adlayer of bound
water molecules, and by (2) interfacial density fluctuations of the bulk liquid
adjacent to the adlayer. We define collective coordinates that describe the
desorption mechanism. Spatial and temporal correlations associated with a
single event extend over nanometers and tens of picoseconds.Comment: 10 pages, 9 figure
Novel flexible heteroarotinoid, SL-1-39, inhibits HER2-positive breast cancer cell proliferation by promoting lysosomal degradation of HER2.
SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells. Molecular analyses suggest that SL-1-39 prevents S phase progression of HER2+ breast cancer cells (SKBR3 and MDA-MB-453), which is consistent with reduced expression of key cell-cycle regulators at both the protein and transcriptional levels. SL-1-39 treatment also decreases the protein levels of HER2 and pHER2 as well as its downstream effectors, pMAPK and pAKT. Reduction of HER2 and pHER2 at the protein level is attributed to increased lysosomal degradation of total HER2 levels. This is the first study to show that a flexible heteroarotinoid analog modulates the HER2 signaling pathway through lysosomal degradation, and thus further warrants the development of SL-1-39 as a therapeutic option for HER2+ breast cancer
The Naas Motorway Bypass - A Cost Benefit Analysis. Quarterly Economic Commentary Special Article, January 1984
The paper examines the Naas Motorway Bypass which cost ÂŁ16m at 1983
prices. Twelve thousand vehicles a day using the bypass save over 10 minutes
between 8 am and 8 pm and 6 minutes at other times. Five thousand vehicles a
day using the present route through Naas also benefit by saving 4 minutes due
to reduced congestion in the town. In addition to time savings, the bypass
reduces accidents and fuel costs. Ninety-one per cent of the benefits accrue in
time savings. The internal rate of return on the project is estimated at 20.51
per cent, assuming 2 per cent annual traffic and income growth. The
sensitivity tests of the results show that even with zero growth in incomes and
traffic for twenty years, a high proportion of leisure time savings with zero
value and no increase in the value of fuel savings the project would have an
internal rate of return which meets the test discount rate used by the
Department of Finance.
The environmental aspects of the bypass are positive in terms of noise and
smoke and lead pollution reduction. The impact on farm severence and
natural amenities on the motorway route has been mitigated by several design
features of the bypass
Sec16p potentiates the action of COPII proteins to bud transport vesicles
SEC16 encodes a 240-kD hydrophilic protein that is required for transport vesicle budding from the ER in Saccharomyces cerevisiae. Sec16p is tightly and peripherally bound to ER membranes, hence it is not one of the cytosolic proteins required to reconstitute transport vesicle budding in a cell-free reaction. However, Sec16p is removed from the membrane by salt washes, and using such membranes we have reconstituted a vesicle budding reaction dependent on the addition of COPII proteins and pure Sec16p. Although COPII vesicle budding is promoted by GTP or a nonhydrolyzable analogue, guanylimide diphosphate (GMP-PNP), Sec16p stimulation is dependent on GTP in the reaction. Details of coat protein assembly and Sec16p-stimulated vesicle budding were explored with synthetic liposomes composed of a mixture of lipids, including acidic phospholipids (majorâminor mix), or a simple binary mixture of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Sec16p binds to majorâminor mix liposomes and facilitates the recruitment of COPII proteins and vesicle budding in a reaction that is stimulated by Sar1p and GMP-PNP. Thin-section electron microscopy confirms a stimulation of budding profiles produced by incubation of liposomes with COPII and Sec16p. Whereas acidic phospholipids in the majorâminor mix are required to recruit pure Sec16p to liposomes, PC/PE liposomes bind Sar1p-GTP, which stimulates the association of Sec16p and Sec23/24p. We propose that Sec16p nucleates a Sar1-GTPâdependent initiation of COPII assembly and serves to stabilize the coat to premature disassembly after Sar1p hydrolyzes GTP
Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinsonâs Disease
Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinsonâs disease (PD). Therapies based on PQâs presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against PQ-induced neuropathology. Our data suggest that exposure to certain environmental toxins promotes accumulation of senescent cells in the aging brain, which can contribute to dopaminergic neurodegeneration. Therapies that target senescent cells may constitute a strategy for treatment of sporadic PD, for which environmental exposure is a major risk factor
Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells
Please see the graphical abstract in the supplemental files
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