3,569 research outputs found
Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies.
This is the final version of the article. It first appeared from Frontiers via https://doi.org/10.3389/fphys.2016.00467Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na+ channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na+, K+, Ca2+, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.GT received a BBSRC Doctoral CASE Studentship at the University of Cambridge and thanks the Croucher Foundation of Hong Kong for the support of his Clinical Assistant Professorship. YC is supported by the ESRC for her Ph.D. studies at the University of Cambridge. BY received funding from the Research Grant Council of Hong Kong for his research
Deep Lesion Graphs in the Wild: Relationship Learning and Organization of Significant Radiology Image Findings in a Diverse Large-scale Lesion Database
Radiologists in their daily work routinely find and annotate significant
abnormalities on a large number of radiology images. Such abnormalities, or
lesions, have collected over years and stored in hospitals' picture archiving
and communication systems. However, they are basically unsorted and lack
semantic annotations like type and location. In this paper, we aim to organize
and explore them by learning a deep feature representation for each lesion. A
large-scale and comprehensive dataset, DeepLesion, is introduced for this task.
DeepLesion contains bounding boxes and size measurements of over 32K lesions.
To model their similarity relationship, we leverage multiple supervision
information including types, self-supervised location coordinates and sizes.
They require little manual annotation effort but describe useful attributes of
the lesions. Then, a triplet network is utilized to learn lesion embeddings
with a sequential sampling strategy to depict their hierarchical similarity
structure. Experiments show promising qualitative and quantitative results on
lesion retrieval, clustering, and classification. The learned embeddings can be
further employed to build a lesion graph for various clinically useful
applications. We propose algorithms for intra-patient lesion matching and
missing annotation mining. Experimental results validate their effectiveness.Comment: Accepted by CVPR2018. DeepLesion url adde
Verticalization of bacterial biofilms
Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms
of rod-shaped bacteria were observed at single-cell resolution and shown to
develop from a disordered, two-dimensional layer of founder cells into a
three-dimensional structure with a vertically-aligned core. Here, we elucidate
the physical mechanism underpinning this transition using a combination of
agent-based and continuum modeling. We find that verticalization proceeds
through a series of localized mechanical instabilities on the cellular scale.
For short cells, these instabilities are primarily triggered by cell division,
whereas long cells are more likely to be peeled off the surface by nearby
vertical cells, creating an "inverse domino effect". The interplay between cell
growth and cell verticalization gives rise to an exotic mechanical state in
which the effective surface pressure becomes constant throughout the growing
core of the biofilm surface layer. This dynamical isobaricity determines the
expansion speed of a biofilm cluster and thereby governs how cells access the
third dimension. In particular, theory predicts that a longer average cell
length yields more rapidly expanding, flatter biofilms. We experimentally show
that such changes in biofilm development occur by exploiting chemicals that
modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15
figure
ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population
Kawasaki disease (KD) is characterized by systemic vasculitis with unknown etiology. Previous studies from Japan indicated that a gene polymorphism of ITPKC (rs28493229) is responsible for susceptibility to KD. We collected DNA samples from 1,531 Taiwanese subjects (341 KD patients and 1,190 controls) for genotyping ITPKC. In this study, no significant association was noted for the ITPKC polymorphism (rs28493229) between the controls and KD patients, although the CC genotype was overrepresented. We further combined our data with previously published case/control KD studies in the Taiwanese population and performed a meta-analysis. A significant association between rs28493229 and KD was found (Odds Ratio:1.36, 95% Confidence Interval 1.12–1.66). Importantly, a significant association was obtained between rs28493229 and KD patients with aneurysm formation (P = 0.001, under the recessive model). Taken together, our results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population
From z>6 to z~2: Unearthing Galaxies at the Edge of the Dark Ages
Galaxies undergoing formation and evolution can now be observed over a time
baseline of some 12 Gyr. An inherent difficulty with high-redshift observations
is that the objects are very faint and the best resolution (HST) is only ~0.5
kpc. Such studies thereby combine in a highly synergistic way with the great
detail that can be obtained for nearby galaxies. 3 new developments are
highlighted. First is the derivation of stellar masses for galaxies from SEDs
using HST and now Spitzer data, and dynamical masses from both sub-mm
observations of CO lines and near-IR observations of optical lines like Halpha.
A major step has been taken with evidence that points to the z~2-3 LBGs having
masses that are a few x 10^10 Msolar. Second is the discovery of a population
of evolved red galaxies at z~2-3 which appear to be the progenitors of the more
massive early-type galaxies of today, with dynamical masses around a few x
10^11 Msolar. Third are the remarkable advances that have occurred in
characterizing dropout galaxies to z~6 and beyond, < 1 Gyr from recombination.
The HST ACS has played a key role here, with the dropout technique being
applied to i & z images in several deep ACS fields, yielding large samples of
these objects. This has allowed a detailed determination of their properties
and meaningful comparisons against lower-z samples. The use of cloning
techniques has overcome many of the strong selection biases affecting the study
of these objects. A clear trend of size with redshift has been identified, and
its impact on the luminosity density and SFR estimated. There is a significant
though modest decrease in the SFR from z~2.5 to z~6. The latest data also allow
for the first robust determination of the LF at z~6. Finally, the latest UDF
ACS and NICMOS data has resulted in the detection of some galaxies at z~7-8.Comment: 18 pages, 8 figures. To appear in Penetrating Bars through Masks of
Cosmic Dust: The Hubble Tuning Fork Strikes a New Note, eds. D. Block, K.
Freeman, R. Groess, I. Puerari, & E.K. Block (Dordrecht: Kluwer), in pres
Mapping the history and current situation of research on John Cunningham virus – a bibliometric analysis
<p>Abstract</p> <p>Background</p> <p>John Cunningham virus (JCV) constitutes a family of polyoma viruses, which plays important roles in the progressive multifocal leukoencephalopathy (PML) and tumorigenesis. However, no bibliometric investigation has been reported to guide the researchers and potential readers.</p> <p>Methods</p> <p>Papers were collected from database Sci-expanded and Pubmed until May 22, 2008. The highly-productive authors, institutes and countries, highly-cited authors and journals were ranked. The highly-cited articles were subjected to co-citation and chronological analysis with highly-frequent MeSH words for co-occurrence analysis.</p> <p>Results</p> <p>Until now, 1785 articles about JCV were indexed in Sci-expanded and 1506 in Pubmed. The main document type was original article. USA, Japan and Italy were the largest three producers about JCV. Temple University published 128 papers and ranked the top, followed by University of Tokyo. Khalili K and Yogo Y became the core authors due to more than 20 documents produced. Journal of Neurovirology published more than 15 papers and ranked the top. Padgett BL and Berger JR were the first two highly-cited authors. Journal of Virology and Journal of Neurovirology respectively ranked to the first two highly-cited journals. These top highly-cited articles were divided into 5 aspects: (1) The correlation between JC virus and tumors; (2) Causal correlation of JCV with PML; (3) Polyoma virus infection and its related diseases in renal-allograft recipients; (4) Detection of JCV antibody, oncogene and its encoding protein; (5) Genetics and molecular biology of JCV. The MeSH/subheadings were classified into five groups: (1) JCV and virus infectious diseases; (2) JCV pathogenicity and pathological appearance of PML; (3) JCV isolation and detection; (4) Immunology of JCV and PML; (5) JCV genetics and tumors.</p> <p>Conclusion</p> <p>JCV investigation mainly focused on its isolation and detection, as well as its correlation with PML and tumors. Establishment of transgenic animal model using JCV T antigen would be a hopeful and useful project in the further study.</p
Identifying Topological Order by Entanglement Entropy
Topological phases are unique states of matter incorporating long-range
quantum entanglement, hosting exotic excitations with fractional quantum
statistics. We report a practical method to identify topological phases in
arbitrary realistic models by accurately calculating the Topological
Entanglement Entropy (TEE) using the Density Matrix Renormalization Group
(DMRG). We argue that the DMRG algorithm naturally produces a minimally
entangled state, from amongst the quasi-degenerate ground states in a
topological phase. This proposal both explains the success of this method, and
the absence of ground state degeneracy found in prior DMRG sightings of
topological phases. We demonstrate the effectiveness of the calculational
procedure by obtaining the TEE for several microscopic models, with an accuracy
of order when the circumference of the cylinder is around ten times
the correlation length. As an example, we definitively show the ground state of
the quantum antiferromagnet on the kagom\'e lattice is a topological
spin liquid, and strongly constrain the full identification of this phase of
matter.Comment: 20 pages, 6 figure
Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle
Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a
pair of isolated flat electronic bands and forms a strongly correlated
electronic platform. Here, we use scanning tunneling microscopy to probe local
properties of highly tunable twisted bilayer graphene devices and show that the
flat bands strongly deform when aligned with the Fermi level. At half filling
of the bands, we observe the development of gaps originating from correlated
insulating states. Near charge neutrality, we find a previously unidentified
correlated regime featuring a substantially enhanced flat band splitting that
we describe within a microscopic model predicting a strong tendency towards
nematic ordering. Our results provide insights into symmetry breaking
correlation effects and highlight the importance of electronic interactions for
all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page
Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations
There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes
The Galaxy Structure-Redshift Relationship
There exists a gradual, but persistent, evolutionary effect in the galaxy
population such that galaxy structure and morphology change with redshift. This
galaxy structure-redshift relationship is such that an increasingly large
fraction of all bright and massive galaxies at redshifts 2 < z < 3 are
morphologically peculiar at wavelengths from rest-frame ultraviolet to
rest-frame optical. There are however examples of morphologically selected
spirals and ellipticals at all redshifts up to z ~ 3. At lower redshift, the
bright galaxy population smoothly transforms into normal ellipticals and
spirals. The rate of this transformation strongly depends on redshift, with the
swiftest evolution occurring between 1 < z < 2. This review characterizes the
galaxy structure-redshift relationship, discusses its various physical causes,
and how these are revealing the mechanisms responsible for galaxy formation.Comment: 20 pages, 8 figures. Invited Review to appear in "Penetrating Bars
Through Masks of Cosmic Dust: The Hubble Tuning Fork Strikes A New Note", ed.
D. Block et a
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