75 research outputs found
The local Gromov-Witten theory of CP^1 and integrable hierarchies
In this paper we begin the study of the relationship between the local
Gromov-Witten theory of Calabi-Yau rank two bundles over the projective line
and the theory of integrable hierarchies. We first of all construct explicitly,
in a large number of cases, the Hamiltonian dispersionless hierarchies that
govern the full descendent genus zero theory. Our main tool is the application
of Dubrovin's formalism, based on associativity equations, to the known results
on the genus zero theory from local mirror symmetry and localization. The
hierarchies we find are apparently new, with the exception of the resolved
conifold O(-1) + O(-1) -> P1 in the equivariantly Calabi-Yau case. For this
example the relevant dispersionless system turns out to be related to the
long-wave limit of the Ablowitz-Ladik lattice. This identification provides us
with a complete procedure to reconstruct the dispersive hierarchy which should
conjecturally be related to the higher genus theory of the resolved conifold.
We give a complete proof of this conjecture for genus g<=1; our methods are
based on establishing, analogously to the case of KdV, a "quasi-triviality"
property for the Ablowitz-Ladik hierarchy at the leading order of the
dispersive expansion. We furthermore provide compelling evidence in favour of
the resolved conifold/Ablowitz-Ladik correspondence at higher genus by testing
it successfully in the primary sector for g=2.Comment: 30 pages; v2: an issue involving constant maps contributions is
pointed out in Sec. 3.3-3.4 and is now taken into account in the proofs of
Thm 1.3-1.4, whose statements are unchanged. Several typos, formulae,
notational inconsistencies have been fixed. v3: typos fixed, minor textual
changes, version to appear on Comm. Math. Phy
Rapid detection of Staphylococcus aureus Panton-Valentine leukocidin in clinical specimens by enzyme-linked immunosorbent assay and immunochromatographic tests
10.1128/JCM.02274-09Journal of Clinical Microbiology4841384-139
Reply to 'Revisiting signatures of neutral tumor evolution in the light of complexity of cancer genomic data'
Exact results for topological strings on resolved Y(p,q) singularities
We obtain exact results in \alpha' for open and closed A-model topological
string amplitudes on a large class of toric Calabi-Yau threefolds by using
their correspondence with five dimensional gauge theories. The toric
Calabi-Yau's that we analyze are obtained as minimal resolution of cones over
Y(p,q) manifolds and give rise via M-theory compactification to SU(p) gauge
theories on R^4 x S^1. As an application we present a detailed study of the
local F_2 case and compute open and closed genus zero Gromov-Witten invariants
of the C^3/Z_4 orbifold. We also display the modular structure of the
topological wave function and give predictions for higher genus amplitudes.The
mirror curve in this case is the spectral curve of the relativistic A_1 Toda
chain. Our results also indicate the existence of a wider class of relativistic
integrable systems associated to generic Y(p,q) geometries.Comment: 54 pages, 10 figures; typos corrected, new section added. Version
accepted for publication on Communications in Mathematical Physic
Characterizing Mutational Heterogeneity in a Glioblastoma Patient with Double Recurrence
Human cancers are driven by the acquisition of somatic mutations. Separating the driving mutations from those that are random consequences of general genomic instability remains a challenge. New sequencing technology makes it possible to detect mutations that are present in only a minority of cells in a heterogeneous tumor population. We sought to leverage the power of ultra-deep sequencing to study various levels of tumor heterogeneity in the serial recurrences of a single glioblastoma multiforme patient. Our goal was to gain insight into the temporal succession of DNA base-level lesions by querying intra- and inter-tumoral cell populations in the same patient over time. We performed targeted “next-generation" sequencing on seven samples from the same patient: two foci within the primary tumor, two foci within an initial recurrence, two foci within a second recurrence, and normal blood. Our study reveals multiple levels of mutational heterogeneity. We found variable frequencies of specific EGFR, PIK3CA, PTEN, and TP53 base substitutions within individual tumor regions and across distinct regions within the same tumor. In addition, specific mutations emerge and disappear along the temporal spectrum from tumor at the time of diagnosis to second recurrence, demonstrating evolution during tumor progression. Our results shed light on the spatial and temporal complexity of brain tumors. As sequencing costs continue to decline and deep sequencing technology eventually moves into the clinic, this approach may provide guidance for treatment choices as we embark on the path to personalized cancer medicine
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK
Cancer Research UK
ERC
H2020
Wellcome Trus
Self-Reported Time in Bed and Sleep Quality in Association with Internalizing and Externalizing Symptoms in School-Age Youth
This study investigated the relationship between self-reported time in bed and sleep quality in association with self-reported internalizing and externalizing symptoms in a sample of 285 elementary school students (52% female) recruited from a rural Midwestern elementary school. Path models were used to estimate proposed associations, controlling for grade level and gender. Curvilinear associations were found between time in bed and anxiety, depressive symptoms, and irritability. Marginal curvilinear trends were found between time in bed and emotion dysregulation, reactive aggression, and proactive aggression. Sleep quality was negatively associated with anxiety, depressive symptoms, irritability, reactive aggression, and delinquency engagement. Gender and grade differences were found across models. Findings suggest that examining self-reported time in bed (both linear and quadratic) and sleep quality is important for understanding internalizing and externalizing symptoms associated with sleep in school-age youth. Incorporating self-reported sleep assessments into clinical practice and school-based evaluations may have implications for a child’s adjustment
ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders
Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders
The RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size
LGR4/5 receptors and their cognate RSPO ligands potentiate Wnt/β-catenin signalling and promote proliferation and tissue homeostasis in epithelial stem cell compartments. In the liver, metabolic zonation requires a Wnt/β-catenin signalling gradient, but the instructive mechanism controlling its spatiotemporal regulation is not known. We have now identified the RSPO-LGR4/5-ZNRF3/RNF43 module as a master regulator of Wnt/β-catenin-mediated metabolic liver zonation. Liver-specific LGR4/5 loss of function (LOF) or RSPO blockade disrupted hepatic Wnt/β-catenin signalling and zonation. Conversely, pathway activation in ZNRF3/RNF43 LOF mice or with recombinant RSPO1 protein expanded the hepatic Wnt/β-catenin signalling gradient in a reversible and LGR4/5-dependent manner. Recombinant RSPO1 protein increased liver size and improved liver regeneration, whereas LGR4/5 LOF caused the opposite effects, resulting in hypoplastic livers. Furthermore, we show that LGR4(+) hepatocytes throughout the lobule contribute to liver homeostasis without zonal dominance. Taken together, our results indicate that the RSPO-LGR4/5-ZNRF3/RNF43 module controls metabolic liver zonation and is a hepatic growth/size rheostat during development, homeostasis and regeneration
Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.
AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791
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