9,382 research outputs found
Structural mechanism underpinning cross-reactivity of a CD8+ T-cell clone that recognises a peptide derived from human telomerase reverse transcriptase
Main Place : a look at a multi-use redevelopment
Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Architecture, 1985.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH.Bibliography: leaves 102-105.by David K. Cole.M.S
Cellular-level versus receptor-level response threshold hierarchies in T-Cell activation
Peptide-MHC (pMHC) ligand engagement by T-cell receptors (TCRs) elicits a variety of cellular responses, some of which require substantially more TCR-mediated stimulation than others. This threshold hierarchy could reside at the receptor level, where different response pathways branch off at different stages of the TCR/CD3 triggering cascade, or at the cellular level, where the cumulative TCR signal registered by the T-cell is compared to different threshold values. Alternatively, dual-level thresholds could exist. In this study, we show that the cellular hypothesis provides the most parsimonious explanation consistent with data obtained from an in-depth analysis of distinct functional responses elicited in a clonal T-cell system by a spectrum of biophysically defined altered peptide ligands across a range of concentrations. Further, we derive a mathematical model that describes how ligand density, affinity, and off-rate all affect signaling in distinct ways. However, under the kinetic regime prevailing in the experiments reported here, the TCR/pMHC class I (pMHCI) dissociation rate was found to be the main governing factor. The CD8 coreceptor modulated the TCR/pMHCI interaction and altered peptide ligand potency. Collectively, these findings elucidate the relationship between TCR/pMHCI kinetics and cellular function, thereby providing an integrated mechanistic understanding of T-cell response profiles
Coherent Cancellation of Photothermal Noise in GaAs/AlGaAs Bragg Mirrors
Thermal noise is a limiting factor in many high-precision optical
experiments. A search is underway for novel optical materials with reduced
thermal noise. One such pair of materials, gallium arsenide and
aluminum-alloyed gallium arsenide (collectively referred to as AlGaAs), shows
promise for its low Brownian noise when compared to conventional materials such
as silica and tantala. However, AlGaAs has the potential to produce a high
level of thermo-optic noise. We have fabricated a set of AlGaAs crystalline
coatings, transferred to fused silica substrates, whose layer structure has
been optimized to reduce thermo-optic noise by inducing coherent cancellation
of the thermoelastic and thermorefractive effects. By measuring the
photothermal transfer function of these mirrors, we find evidence that this
optimization has been successful.Comment: 10 pages, 7 figure
Radiation-Pressure-Mediated Control of an Optomechanical Cavity
We describe and demonstrate a method to control a detuned movable-mirror
Fabry-Perot cavity using radiation pressure in the presence of a strong optical
spring. At frequencies below the optical spring resonance, self-locking of the
cavity is achieved intrinsically by the optomechanical (OM) interaction between
the cavity field and the movable end mirror. The OM interaction results in a
high rigidity and reduced susceptibility of the mirror to external forces.
However, due to a finite delay time in the cavity, this enhanced rigidity is
accompanied by an anti-damping force, which destabilizes the cavity. The cavity
is stabilized by applying external feedback in a frequency band around the
optical spring resonance. The error signal is sensed in the amplitude
quadrature of the transmitted beam with a photodetector. An amplitude modulator
in the input path to the cavity modulates the light intensity to provide the
stabilizing radiation pressure force
A network-based ranking system for American college football
American college football faces a conflict created by the desire to stage
national championship games between the best teams of a season when there is no
conventional playoff system to decide which those teams are. Instead, ranking
of teams is based on their record of wins and losses during the season, but
each team plays only a small fraction of eligible opponents, making the system
underdetermined or contradictory or both. It is an interesting challenge to
create a ranking system that at once is mathematically well-founded, gives
results in general accord with received wisdom concerning the relative
strengths of the teams, and is based upon intuitive principles, allowing it to
be accepted readily by fans and experts alike. Here we introduce a
one-parameter ranking method that satisfies all of these requirements and is
based on a network representation of college football schedules.Comment: 15 pages, 3 figure
Dark Matter and Stellar Mass in the Luminous Regions of Disk Galaxies
We investigate the correlations among stellar mass (M_*), disk scale length
(R_d), and rotation velocity at 2.2 disk scale lengths (V_2.2) for a sample of
81 disk-dominated galaxies (disk/total >= 0.9) selected from the SDSS. We
measure V_2.2 from long-slit H-alpha rotation curves and infer M_* from galaxy
i-band luminosities (L_i) and g-r colors. We find logarithmic slopes of
2.60+/-0.13 and 3.05+/-0.12 for the L_i-V_2.2 and M_*-V_2.2 relations, somewhat
shallower than most previous studies, with intrinsic scatter of 0.13 dex and
0.16 dex. Our direct estimates of the total-to-stellar mass ratio within
2.2R_d, assuming a Kroupa IMF, yield a median ratio of 2.4 for M_*>10^10 Msun
and 4.4 for M_*=10^9-10^10 Msun, with large scatter at a given M_* and R_d. The
typical ratio of the rotation speed predicted for the stellar disk alone to the
observed rotation speed at 2.2R_d is ~0.65. The distribution of R_d at fixed
M_* is broad, but we find no correlation between disk size and the residual
from the M_*-V_2.2 relation, implying that this relation is an approximately
edge-on view of the disk galaxy fundamental plane. Independent of the assumed
IMF, this result implies that stellar disks do not, on average, dominate the
mass within 2.2R_d. We discuss our results in the context of infall models of
disk formation in cold dark matter halos. A model with a disk-to-halo mass
ratio m_d=0.05 provides a reasonable match to the R_d-M_* distribution for spin
parameters \lambda ranging from ~0.04-0.08, and it yields a reasonable match to
the mean M_*-V_2.2 relation. A model with m_d=0.1 predicts overly strong
correlations between disk size and M_*-V_2.2 residual. Explaining the wide
range of halo-to-disk mass ratios within 2.2R_d requires significant scatter in
m_d values, with systematically lower m_d for galaxies with lower .Comment: 18 pages, 2 tables, 7 figures, Accepted to ApJ, Table 1 updated,
otherwise minor change
Reliable in silico ranking of engineered therapeutic TCR binding affinities with MMPB/GBSA
Accurate and efficient in silico ranking of proteinprotein binding affinities is useful for protein design with applications in biological therapeutics. One popular approach to rank binding affinities is to apply the molecular mechanics Poisson-Boltzmann/generalized Born surface area (MMPB/ GBSA) method to molecular dynamics (MD) trajectories. Here, we identify protocols that enable the reliable evaluation of T-cell receptor (TCR) variants binding to their target, peptide-human leukocyte antigens (pHLAs). We suggest different protocols for variant sets with a few (<= 4) or many mutations, with entropy corrections important for the latter. We demonstrate how potential outliers could be identified in advance and that just 5-10 replicas of short (4 ns) MD simulations may be sufficient for the reproducible and accurate ranking of TCR variants. The protocols developed here can be applied toward in silico screening during the optimization of therapeutic TCRs, potentially reducing both the cost and time taken for biologic development
Determination of the Baryon Density from Large Scale Galaxy Redshift Surveys
We estimate the degree to which the baryon density, , can be
determined from the galaxy power spectrum measured from large scale galaxy
redshift surveys, and in particular, the Sloan Digital Sky Survey. A high
baryon density will cause wiggles to appear in the power spectrum, which should
be observable at the current epoch. We assume linear theory on scales and do not include the effects of redshift distortions, evolution,
or biasing. With an optimum estimate of to ,
the uncertainties in are roughly 0.07 and 0.016 in flat
and open () cosmological models, respectively. This result
suggests that it should be possible to test for consistency with big bang
nucleosynthesis estimates of if we live in an open universe.Comment: 23 Pages, 10 Postscript figure
Hadronic Resonances from Lattice QCD
The determination of the pattern of hadronic resonances as predicted by
Quantum Chromodynamics requires the use of non-perturbative techniques. Lattice
QCD has emerged as the dominant tool for such calculations, and has produced
many QCD predictions which can be directly compared to experiment. The concepts
underlying lattice QCD are outlined, methods for calculating excited states are
discussed, and results from an exploratory Nucleon and Delta baryon spectrum
study are presented.Comment: 8 pages, VII Latin American Symposium on Nuclear Physics and
Application
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