2,343 research outputs found
Probabilistic Clustering of Time-Evolving Distance Data
We present a novel probabilistic clustering model for objects that are
represented via pairwise distances and observed at different time points. The
proposed method utilizes the information given by adjacent time points to find
the underlying cluster structure and obtain a smooth cluster evolution. This
approach allows the number of objects and clusters to differ at every time
point, and no identification on the identities of the objects is needed.
Further, the model does not require the number of clusters being specified in
advance -- they are instead determined automatically using a Dirichlet process
prior. We validate our model on synthetic data showing that the proposed method
is more accurate than state-of-the-art clustering methods. Finally, we use our
dynamic clustering model to analyze and illustrate the evolution of brain
cancer patients over time
The relation of steady evaporating drops fed by an influx and freely evaporating drops
We discuss a thin film evolution equation for a wetting evaporating liquid on
a smooth solid substrate. The model is valid for slowly evaporating small
sessile droplets when thermal effects are insignificant, while wettability and
capillarity play a major role. The model is first employed to study steady
evaporating drops that are fed locally through the substrate. An asymptotic
analysis focuses on the precursor film and the transition region towards the
bulk drop and a numerical continuation of steady drops determines their fully
non-linear profiles.
Following this, we study the time evolution of freely evaporating drops
without influx for several initial drop shapes. As a result we find that drops
initially spread if their initial contact angle is larger than the apparent
contact angle of large steady evaporating drops with influx. Otherwise they
recede right from the beginning
Reaction rates and transport in neutron stars
Understanding signals from neutron stars requires knowledge about the
transport inside the star. We review the transport properties and the
underlying reaction rates of dense hadronic and quark matter in the crust and
the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of
Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes,
references updated, overview graphic added in the introduction, improvements
in Sec IV.A.
What is Quantum? Unifying Its Micro-Physical and Structural Appearance
We can recognize two modes in which 'quantum appears' in macro domains: (i) a
'micro-physical appearance', where quantum laws are assumed to be universal and
they are transferred from the micro to the macro level if suitable 'quantum
coherence' conditions (e.g., very low temperatures) are realized, (ii) a
'structural appearance', where no hypothesis is made on the validity of quantum
laws at a micro level, while genuine quantum aspects are detected at a
structural-modeling level. In this paper, we inquire into the connections
between the two appearances. We put forward the explanatory hypothesis that,
'the appearance of quantum in both cases' is due to 'the existence of a
specific form of organisation, which has the capacity to cope with random
perturbations that would destroy this organisation when not coped with'. We
analyse how 'organisation of matter', 'organisation of life', and 'organisation
of culture', play this role each in their specific domain of application, point
out the importance of evolution in this respect, and put forward how our
analysis sheds new light on 'what quantum is'.Comment: 10 page
Fully gapped topological surface states in BiSe films induced by a d-wave high-temperature superconductor
Topological insulators are a new class of materials, that exhibit robust
gapless surface states protected by time-reversal symmetry. The interplay
between such symmetry-protected topological surface states and symmetry-broken
states (e.g. superconductivity) provides a platform for exploring novel quantum
phenomena and new functionalities, such as 1D chiral or helical gapless
Majorana fermions, and Majorana zero modes which may find application in
fault-tolerant quantum computation. Inducing superconductivity on topological
surface states is a prerequisite for their experimental realization. Here by
growing high quality topological insulator BiSe films on a d-wave
superconductor BiSrCaCuO using molecular beam epitaxy,
we are able to induce high temperature superconductivity on the surface states
of BiSe films with a large pairing gap up to 15 meV. Interestingly,
distinct from the d-wave pairing of BiSrCaCuO, the
proximity-induced gap on the surface states is nearly isotropic and consistent
with predominant s-wave pairing as revealed by angle-resolved photoemission
spectroscopy. Our work could provide a critical step toward the realization of
the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274
Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy
Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies
Ethnic disparities in progression rates for sight-threatening diabetic retinopathy in diabetic eye screening: a population-based retrospective cohort study
INTRODUCTION: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse multi-ethnic population.
RESEARCH DESIGN AND METHODS: North East London DESP cohort data (January 2012 to December 2021) with 137 591 PLD with no retinopathy, or non-STDR at baseline in one/both eyes, were used to calculate STDR incidence rates by sociodemographic factors, diabetes type, and duration. HR from Cox models examined associations with STDR.
RESULTS: There were 16 388 incident STDR cases over a median of 5.4 years (IQR 2.8-8.2; STDR rate 2.214, 95% CI 2.214 to 2.215 per 100 person-years). People with no retinopathy at baseline had a lower risk of sight-threatening diabetic retinopathy (STDR) compared with those with non-STDR in one eye (HR 3.03, 95% CI 2.91 to 3.15, p<0.001) and both eyes (HR 7.88, 95% CI 7.59 to 8.18, p<0.001). Black and South Asian individuals had higher STDR hazards than white individuals (HR 1.57, 95% CI 1.50 to 1.64 and HR 1.36, 95% CI 1.31 to 1.42, respectively). Additionally, every 5-year increase in age at inclusion was associated with an 8% reduction in STDR hazards (p<0.001). CONCLUSIONS: Ethnic disparities exist in a health system limited by capacity rather than patient economic circumstances. Diabetic retinopathy at first screen is a strong determinant of STDR development. By using basic demographic characteristics, screening programmes or clinical practices can stratify risk for sight-threatening diabetic retinopathy development
Two-year recall for people with no diabetic retinopathy: A multi-ethnic population-based retrospective cohort study using real-world data to quantify the effect
BACKGROUND/AIMS: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual screening. Less frequent screening has been advocated among PLD without diabetic retinopathy (DR), but evidence for each ethnic group is limited. We examined the potential effect of biennial versus annual screening on the detection of sight-threatening diabetic retinopathy (STDR) and proliferative diabetic retinopathy (PDR) among PLD without DR from a large urban multi-ethnic English DESP. METHODS: PLD in North-East London DESP (January 2012 to December 2021) with no DR on two prior consecutive screening visits with up to 8 years of follow-up were examined. Annual STDR and PDR incidence rates, overall and by ethnicity, were quantified. Delays in identification of STDR and PDR events had 2-year screening intervals been used were determined. FINDINGS: Among 82 782 PLD (37% white, 36% South Asian, and 16% black people), there were 1788 incident STDR cases over mean (SD) 4.3 (2.4) years (STDR rate 0.51, 95% CI 0.47 to 0.55 per 100-person-years). STDR incidence rates per 100-person-years by ethnicity were 0.55 (95% CI 0.48 to 0.62) for South Asian, 0.34 (95% CI 0.29 to 0.40) for white, and 0.77 (95% CI 0.65 to 0.90) for black people. Biennial screening would have delayed diagnosis by 1 year for 56.3% (1007/1788) with STDR and 43.6% (45/103) with PDR. Standardised cumulative rates of delayed STDR per 100 000 persons for each ethnic group were 1904 (95% CI 1683 to 2154) for black people, 1276 (95% CI 1153 to 1412) for South Asian people, and 844 (95% CI 745 to 955) for white people. INTERPRETATION: Biennial screening would have delayed detection of some STDR and PDR by 1 year, especially among those of black ethnic origin, leading to healthcare inequalities
Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.
Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer
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
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