39 research outputs found
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A computational exploration of resilience and evolvability of protein–protein interaction networks
Protein-protein interaction (PPI) networks represent complex intra-cellular protein interactions , and the presence or absence of such interactions can lead to biological changes in an organism. Recent network-based approaches have shown that a phenotype's PPI network's resilience to environmental perturbations is related to its placement in the tree of life; though we still do not know how or why certain intra-cellular factors can bring about this resilience. Here, we explore the influence of gene expression and network properties on PPI networks' resilience. We use publicly available data of PPIs for E. coli, S. cerevisiae, and H. sapiens, where we compute changes in network resilience as new nodes (proteins) are added to the networks under three node addition mechanisms-random, degree-based, and gene-expression-based attachments. By calculating the resilience of the resulting networks, we estimate the effectiveness of these node addition mechanisms. We demonstrate that adding nodes with gene-expression-based preferential attachment (as opposed to random or degree-based) preserves and can increase the original resilience of PPI network in all three species, regardless of gene expression distribution or network structure. These findings introduce a general notion of prospective resilience, which highlights the key role of network structures in understanding the evolvability of phenotypic traits
Ultrasensitive force and displacement detection using trapped ions
The ability to detect extremely small forces is vital for a variety of
disciplines including precision spin-resonance imaging, microscopy, and tests
of fundamental physical phenomena. Current force-detection sensitivity limits
have surpassed 1 (atto ) through coupling of micro or
nanofabricated mechanical resonators to a variety of physical systems including
single-electron transistors, superconducting microwave cavities, and individual
spins. These experiments have allowed for probing studies of a variety of
phenomena, but sensitivity requirements are ever-increasing as new regimes of
physical interactions are considered. Here we show that trapped atomic ions are
exquisitely sensitive force detectors, with a measured sensitivity more than
three orders of magnitude better than existing reports. We demonstrate
detection of forces as small as 174 (yocto ), with a
sensitivity 390 using crystals of Be
ions in a Penning trap. Our technique is based on the excitation of normal
motional modes in an ion trap by externally applied electric fields, detection
via and phase-coherent Doppler velocimetry, which allows for the discrimination
of ion motion with amplitudes on the scale of nanometers. These experimental
results and extracted force-detection sensitivities in the single-ion limit
validate proposals suggesting that trapped atomic ions are capable of detecting
of forces with sensitivity approaching 1 . We anticipate that
this demonstration will be strongly motivational for the development of a new
class of deployable trapped-ion-based sensors, and will permit scientists to
access new regimes in materials science.Comment: Expanded introduction and analysis. Methods section added. Subject to
press embarg
Delocalized single-photon Dicke states and the Leggett- Garg inequality in solid state systems
We show how to realize a single-photon Dicke state in a large one-dimensional
array of two- level systems, and discuss how to test its quantum properties.
Realization of single-photon Dicke states relies on the cooperative nature of
the interaction between a field reservoir and an array of two-level-emitters.
The resulting dynamics of the delocalized state can display Rabi-like
oscillations when the number of two-level emitters exceeds several hundred. In
this case the large array of emitters is essentially behaving like a
mirror-less cavity. We outline how this might be realized using a
multiple-quantum-well structure and discuss how the quantum nature of these
oscillations could be tested with the Leggett-Garg inequality and its
extensions.Comment: 29 pages, 5 figures, journal pape
Atypical emotional anticipation in high-functioning autism
"Background: Understanding and anticipating others’ mental or emotional states relies on the processing of social
cues, such as dynamic facial expressions. Individuals with high-functioning autism (HFA) may process these cues
differently from individuals with typical development (TD) and purportedly use a ‘mechanistic’ rather than a
‘mentalistic’ approach, involving rule- and contingency-based interpretations of the stimuli. The study primarily
aimed at examining whether the judgments of facial expressions made by individuals with TD and HFA would be
similarly affected by the immediately preceding dynamic perceptual history of that face. A second aim was to
explore possible differences in the mechanisms underpinning the perceptual judgments in the two groups.
Methods: Twenty-two adults with HFA and with TD, matched for age, gender and IQ, were tested in three
experiments in which dynamic, ‘ecologically valid’ offsets of happy and angry facial expressions were presented.
Participants evaluated the expression depicted in the last frame of the video clip by using a 5-point scale ranging
from slightly angry via neutral to slightly happy. Specific experimental manipulations prior to the final facial
expression of the video clip allowed examining contributions of bottom-up mechanisms (sequential contrast/
context effects and representational momentum) and a top-down mechanism (emotional anticipation) to
distortions in the perception of the final expression.
Results: In experiment 1, the two groups showed a very similar perceptual bias for the final expression of joy-to-neutral
and anger-to-neutral videos (overshoot bias). In experiment 2, a change in the actor’s identity during the clip removed
the bias in the TD group, but not in the HFA group. In experiment 3, neutral-to-joy/anger-to-neutral sequences generated
an undershoot bias (opposite to the overshoot) in the TD group, whereas no bias was observed in the HFA group.
Conclusions: We argue that in TD individuals the perceptual judgments of other’s facial expressions were underpinned
by an automatic emotional anticipation mechanism. In contrast, HFA individuals were primarily influenced by visual
features, most notably the contrast between the start and end expressions, or pattern extrapolation. We critically discuss
the proposition that automatic emotional anticipation may be induced by motor simulation of the perceived dynamic
facial expressions and discuss its implications for autism.
The Polarised Valence Quark Distribution from semi-inclusive DIS
The semi-inclusive difference asymmetry A^{h^{+}-h^{-}} for hadrons of
opposite charge has been measured by the COMPASS experiment at CERN. The data
were collected in the years 2002-2004 using a 160 GeV polarised muon beam
scattered off a large polarised ^6LiD target and cover the range 0.006 < x <
0.7 and 1 < Q^2 < 100 (GeV/c)^2. In leading order QCD (LO) the asymmetry
A_d^{h^{+}-h^{-}} measures the valence quark polarisation and provides an
evaluation of the first moment of Delta u_v + Delta d_v which is found to be
equal to 0.40 +- 0.07 (stat.) +- 0.05 (syst.) over the measured range of x at
Q^2 = 10 (GeV/c)^2. When combined with the first moment of g_1^d previously
measured on the same data, this result favours a non-symmetric polarisation of
light quarks Delta u-bar = - Delta d-bar at a confidence level of two standard
deviations, in contrast to the often assumed symmetric scenario Delta u-bar =
Delta d-bar = Delta s-bar = Delta s.Comment: 7 pages, 3 figures, COMPASS, revised: details added, author list
update
Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease
Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions
Laser-induced rotation and cooling of a trapped microgyroscope in vacuum
This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC grant numbers: EP/J01771X/1 and EP/G061688/1)Quantum state preparation of mesoscopic objects is a powerful playground for the elucidation of many physical principles. The field of cavity optomechanics aims to create these states through laser cooling and by minimizing state decoherence. Here we demonstrate simultaneous optical trapping and rotation of a birefringent microparticle in vacuum using a circularly polarized trapping laser beam—a microgyroscope. We show stable rotation rates up to 5 MHz. Coupling between the rotational and translational degrees of freedom of the trapped microgyroscope leads to the observation of positional stabilization in effect cooling the particle to 40 K. We attribute this cooling to the interaction between the gyroscopic directional stabilization and the optical trapping field.Publisher PDFPeer reviewe