7,284 research outputs found
A Possible Nanometer-scale Computing Device Based on an Adding Cellular Automaton
We present a simple one-dimensional Cellular Automaton (CA) which has the
property that an initial state composed of two binary numbers evolves quickly
into a final state which is their sum. We call this CA the Adding Cellular
Automaton (ACA). The ACA requires only 2N two-state cells in order to add any
two N-1 bit binary numbers. The ACA could be directly realized as a wireless
nanometer-scale computing device - a possible implementation using coupled
quantum dots is outlined.Comment: 8 pages, RevTex, 3 Postscript figures. This version to appear in App.
Phys. Let
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Engineering Probes to Detect Cholesterol Accessibility on Membranes Using Perfringolysin O
Cholesterol is an essential component of mammalian cell membranes and it is important to regulate the structure and function of lipid bilayers. Changes in cholesterol levels are involved in many physiological and pathological events such as the formation of arterial plaques, viral entry into cells, sperm capacitation, and receptor organization. Determination of cholesterol trafficking and distribution is essential for understanding how cells regulate cholesterol.
A key factor in the regulation of cholesterol is cholesterol accessibility. Through it interactions in the membrane, cholesterol is sequestered below the surface of the membrane. Based on the composition of the membrane, a certain amount of cholesterol can be solubilized through interaction with the membrane. The remaining cholesterol is more solvent exposed and therefor accessible to interact with molecules outside of the membrane. This accessible cholesterol is thought to regulate cholesterol homeostasis within the cell. A cholesterol probe capable of distinguishing changes in cholesterol accessibility within membranes would facilitate investigations in this area.
Perfringolysin O (PFO) is a cytolysin secreted by Clostridium perfringens that requires cholesterol in the target cell membrane for binding. The specificity of PFO for high levels of accessible cholesterol makes this toxin a potential tool for the detection of cholesterol distribution and trafficking. In an effort to adapt PFO into a molecular probe capable of sensing changes in membrane cholesterol accessibility, I have taken a non-lytic derivative of PFO and introduced several point mutations in the membrane-interacting domain 4 loops. These mutations altered the threshold of cholesterol concentration required in the membrane to trigger binding.
The cholesterol-dependent binding of each PFO derivative was tested on model membranes containing different percentages of cholesterol. Three PFO derivatives were selected to test their binding to macrophage plasma membranes. These three derivatives showed differential binding to cell membranes treated with β-methyl-cyclodextrin/cholesterol mixtures. These data showed that the produced PFO derivatives differentially bind to model and biological membranes containing different cholesterol accessibility
The Supreme Court, Question-Selection, Legitimacy, and Reform: Three Theorems and One Suggestion
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Maladaptive behavior and affect regulation: A functionalist perspective.
Clinical science has benefited tremendously from taking seriously the proposition that putatively maladaptive behaviors serve psychological functions, prominently among these affect regulation (AR). These functionalist accounts have not only advanced basic clinical science, but also formed the bedrock for the development of effective treatments. Drawing heavily on reinforcement learning theory, we aim to elucidate functional relationships between maladaptive behavior and AR. Specifically, we take the view that maladaptive behaviors are frequently motivated and reinforced by hedonic AR functions (i.e., decreasing negative affect and increasing positive affect) but are also susceptible to becoming stimulus-bound habits. We review empirical evidence related to one such behavior, nonsuicidal self-injury. We close with a brief reflection on future directions. (PsycINFO Database Record (c) 2020 APA, all rights reserved)
Companions to peculiar red giants: HR 363 and HR 1105
Recent IUE observations of two Tc-deficient S-type peculiar red giants that are also spectroscopic binaries, HR 363 and HR 1105 are reported. A 675 min SWP exposure of HR 363 shows emission lines of O I 1304 and Si II 1812 and a trace of continuum. Compared to the M giants, the far UV flux may be relatively larger, indicating a possible contribution from a white dwarf companion, but no high temperature emission lines are seen to indicate that this is an interacting system where mass-transfer recently occurred. However, HR 1105 appears to have a highly variable UV companion. In 1982, no UV flux was discerned for this system, but by 1986 C IV was strong, increasing by a factor of 3 in 1987 with prominent lines of Si III, C III, O III, Si IV, and N V. Using orbital parameters, these observations are consistent with high activity occuring when the side of the S-star primary illuminated by the companion faces the Earth, but since the IUE data were taken over 3 orbits, a secular change in the UV component cannot be excluded
Optimal combinations of imperfect objects
We address the question of how to make best use of imperfect objects, such as
defective analog and digital components. We show that perfect, or near-perfect,
devices can be constructed by taking combinations of such defects. Any
remaining objects can be recycled efficiently. In addition to its practical
applications, our `defect combination problem' provides a novel generalization
of classical optimization problems.Comment: 4 pages, 3 figures, minor change
Mechanistic Insights into the Cholesterol-dependent Binding of Perfringolysin O-based Probes and Cell Membranes
Cholesterol distribution in the cell is maintained by both vesicular and non-vesicular sterol transport. Non-vesicular transport is mediated by the interaction of membrane-embedded cholesterol and water-soluble proteins. Small changes to the lipid composition of the membrane that do not change the total cholesterol content, can significantly affect how cholesterol interacts with other molecules at the surface of the membrane. The cholesterol-dependent cytolysin Perfringolysin O (PFO) constitutes a powerful tool to detect cholesterol in membranes, and the use of PFO-based probes has flourished in recent years. By using a non-lytic PFO derivative, we showed that the sensitivity of the probes for cholesterol can be tuned by modifications introduced directly in the membrane-interacting loops and/or by modifying residues away from the membrane-interacting domain. Through the use of these biosensors on live RAW 264.7 cells, we found that changes in the overall cholesterol content have a limited effect on the average cholesterol accessibility at the surface of the membrane. We showed that these exquisite biosensors report on changes in cholesterol reactivity at the membrane surface independently of the overall cholesterol content in the membrane
Body Mass Index and Cognitive Decline in Mild Cognitive Impairment
This is the author's accepted manuscript.Objective
To examine the relationship between body mass index (BMI) and cognitive decline in subjects diagnosed with mild cognitive impairment (MCI).
Methods
Neuropsychologic and clinical evaluations were conducted at baseline, 6-months, and 1-year on 286 MCI subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative. A global cognitive composite score was derived (mean Z-score) from performance on 9 neuropsychologic subtests. Height and weight were assessed at baseline and used to calculate BMI. Generalized estimating equations (linear and logistic) assessed the relationships of baseline BMI with cognitive outcomes, clinician judgment of “clinically significant decline” over 1-year, and diagnostic progression from MCI to Alzheimer disease.
Results
Lower baseline BMI was associated with significant declines in cognitive performance in individuals with MCI over 1 year (Mini-Mental State Examination, Alzheimer Disease Assessment Scale-Cognitive subscale, and a global cognitive composite; all P<0.05). We observed a significant protective effect of baseline BMI in reducing the risk of a clinically significant decline in Alzheimer Disease Assessment Scale-Cognitive subscale and mini-mental state examination (P<0.05). No association was found between BMI and changes in the clinical dementia rating sum of boxes or conversion to Alzheimer disease.
Conclusions
Lower baseline BMI is associated with more rapid cognitive decline in MCI. This relationship suggests either body composition may influence the rate of cognitive decline in MCI or factors related to MCI influence body composition
KELT-23Ab: A Hot Jupiter Transiting a Near-solar Twin Close to the TESS and JWST Continuous Viewing Zones
We announce the discovery of KELT-23Ab, a hot Jupiter transiting the relatively bright (V = 10.3) star BD+66 911 (TYC 4187-996-1), and characterize the system using follow-up photometry and spectroscopy. A global fit to the system yields host-star properties of T_(eff)=5900±49K, M∗=0.945^(+0.060)_(−0.054)M⊙, R∗=0.995±0.015R⊙, L∗=1.082^(+0.051)_(−0.048)L⊙, logg∗=4.418^(+0.026)_(−0.025) (cgs), and [Fe/H]=−0.105±0.077. KELT-23Ab is a hot Jupiter with a mass of MP=0.938^(+0.045)_(−0.042)M_J, radius of R_P=1.322±0.025RJ, and density of ρ_P=0.504^(+0.038)_(−0.035) g cm^(−3). Intense insolation flux from the star has likely caused KELT-23Ab to become inflated. The time of inferior conjunction is
T_0=2458149.40776±0.00091 BJD_(TDB) and the orbital period is P=2.255353^(+0.000031)_(−0.00003) days. There is strong evidence that KELT-23A is a member of a long-period binary star system with a less luminous companion, and due to tidal interactions, the planet is likely to spiral into its host within roughly a gigayear. This system has one of the highest positive ecliptic latitudes of all transiting planet hosts known to date, placing it near the Transiting Planet Survey Satellite and James Webb Space Telescope continuous viewing zones. Thus we expect it to be an excellent candidate for long-term monitoring and follow up with these facilities
The TRENDS High-Contrast Imaging Survey. VI. Discovery of a Mass, Age, and Metallicity Benchmark Brown Dwarf
The mass and age of substellar objects are degenerate parameters leaving the
evolutionary state of brown dwarfs ambiguous without additional information.
Theoretical models are normally used to help distinguish between old, massive
brown dwarfs and young, low mass brown dwarfs but these models have yet to be
properly calibrated. We have carried out an infrared high-contrast imaging
program with the goal of detecting substellar objects as companions to nearby
stars to help break degeneracies in inferred physical properties such as mass,
age, and composition. Rather than using imaging observations alone, our targets
are pre-selected based on the existence of dynamical accelerations informed
from years of stellar radial velocity (RV) measurements. In this paper, we
present the discovery of a rare benchmark brown dwarf orbiting the nearby
( pc), solar-type (G9V) star HD 4747 ([Fe/H]=)
with a projected separation of only AU (
0.6"). Precise Doppler measurements taken over 18 years reveal the companion's
orbit and allow us to place strong constraints on its mass using dynamics (). Relative photometry (,
, ) indicates that HD 4747 B is
most-likely a late-type L-dwarf and, if near the L/T transition, an intriguing
source for studying cloud physics, variability, and polarization. We estimate a
model-dependent mass of for an age of
Gyr based on gyrochronology. Combining astrometric measurements with RV data,
we calculate the companion dynamical mass () and orbit
() directly. As a new mass, age, and metallicity benchmark, HD
4747 B will serve as a laboratory for precision astrophysics to test
theoretical models that describe the emergent radiation of brown dwarfs.Comment: Accepted to Ap
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