3,392 research outputs found

    On-Line Learning with Restricted Training Sets: An Exactly Solvable Case

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    We solve the dynamics of on-line Hebbian learning in large perceptrons exactly, for the regime where the size of the training set scales linearly with the number of inputs. We consider both noiseless and noisy teachers. Our calculation cannot be extended to non-Hebbian rules, but the solution provides a convenient and welcome benchmark with which to test more general and advanced theories for solving the dynamics of learning with restricted training sets.Comment: 19 pages, eps figures included, uses epsfig macr

    The EMT-activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but is predictive of survival

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    The IGROVCDDP cisplatin-resistant ovarian cancer cell line is an unusual model, as it is also cross-resistant to paclitaxel. IGROVCDDP, therefore, models the resistance phenotype of serous ovarian cancer patients who have failed frontline platinum/taxane chemotherapy. IGROVCDDP has also undergone epithelial-mesenchymal transition (EMT). We aim to determine if alterations in EMT-related genes are related to or independent from the drug-resistance phenotypes. EMT gene and protein markers, invasion, motility and morphology were investigated in IGROVCDDP and its parent drug-sensitive cell line IGROV-1. ZEB1 was investigated by qPCR, Western blotting and siRNA knockdown. ZEB1 was also investigated in publicly available ovarian cancer gene-expression datasets. IGROVCDDP cells have decreased protein levels of epithelial marker E-cadherin (6.18-fold, p = 1.58e−04) and higher levels of mesenchymal markers vimentin (2.47-fold, p = 4.43e−03), N-cadherin (4.35-fold, p = 4.76e−03) and ZEB1 (3.43-fold, p = 0.04). IGROVCDDP have a spindle-like morphology consistent with EMT. Knockdown of ZEB1 in IGROVCDDP does not lead to cisplatin sensitivity but shows a reversal of EMT-gene signalling and an increase in cell circularity. High ZEB1 gene expression (HR = 1.31, n = 2051, p = 1.31e−05) is a marker of poor overall survival in high-grade serous ovarian-cancer patients. In contrast, ZEB1 is not predictive of overall survival in high-grade serous ovarian-cancer patients known to be treated with platinum chemotherapy. The increased expression of ZEB1 in IGROVCDDP appears to be independent of the drug-resistance phenotypes. ZEB1 has the potential to be used as biomarker of overall prognosis in ovarian-cancer patients but not of platinum/taxane chemoresistance

    Exciton-assisted optomechanics with suspended carbon nanotubes

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    We propose a framework for inducing strong optomechanical effects in a suspended carbon nanotube based on deformation potential exciton-phonon coupling. The excitons are confined using an inhomogeneous axial electric field which generates optically active quantum dots with a level spacing in the milli-electronvolt range and a characteristic size in the 10-nanometer range. A transverse field induces a tunable parametric coupling between the quantum dot and the flexural modes of the nanotube mediated by electron-phonon interactions. We derive the corresponding excitonic deformation potentials and show that this interaction enables efficient optical ground-state cooling of the fundamental mode and could allow us to realise the strong and ultra-strong coupling regimes of the Jaynes-Cummings and Rabi models.Comment: 25 pages, 2 figure

    Constraining quasar host halo masses with the strength of nearby Lyman-alpha forest absorption

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    Using cosmological hydrodynamic simulations we measure the mean transmitted flux in the Lyman alpha forest for quasar sightlines that pass near a foreground quasar. We find that the trend of absorption with pixel-quasar separation distance can be fitted using a simple power law form including the usual correlation function parameters r_{0} and \gamma so that ( = \sum exp(-tau_eff*(1+(r/r_{0})^(-\gamma)))). From the simulations we find the relation between r_{0} and quasar mass and formulate this as a way to estimate quasar host dark matter halo masses, quantifying uncertainties due to cosmological and IGM parameters, and redshift errors. With this method, we examine data for ~3000 quasars from the Sloan Digital Sky Survey (SDSS) Data Release 3, assuming that the effect of ionizing radiation from quasars (the so-called transverse proximity effect) is unimportant (no evidence for it is seen in the data.) We find that the best fit host halo mass for SDSS quasars with mean redshift z=3 and absolute G band magnitude -27.5 is log10(M/M_sun) = 12.48^{+0.53}_{-0.89}. We also use the Lyman-Break Galaxy (LBG) and Lyman alpha forest data of Adelberger et al in a similar fashion to constrain the halo mass of LBGs to be log10(M/M_sun) = 11.13^{+0.39}_{-0.55}, a factor of ~20 lower than the bright quasars. In addition, we study the redshift distortions of the Lyman alpha forest around quasars, using the simulations. We use the quadrupole to monopole ratio of the quasar-Lyman alpha forest correlation function as a measure of the squashing effect. We find that this does not have a measurable dependence on halo mass, but may be useful for constraining cosmic geometry.Comment: 10 pages, 11 figures, submitted to MNRA

    Repeatability of brain phase-based magnetic resonance electric properties tomography methods and effect of compressed SENSE and RF shimming

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    Magnetic resonance electrical properties tomography (MREPT) is an emerging imaging modality to noninvasively measure tissue conductivity and permittivity. Implementation of MREPT in the clinic requires repeatable measurements at a short scan time and an appropriate protocol. The aim of this study was to investigate the repeatability of conductivity measurements using phase-based MREPT and the effects of compressed SENSE (CS), and RF shimming on the precision of conductivity measurements. Conductivity measurements using turbo spin echo (TSE) and three-dimensional balanced fast field echo (bFFE) with CS factors were repeatable. Conductivity measurement using bFFE phase showed smaller mean and variance that those measured by TSE. The conductivity measurements using bFFE showed minimal deviation with CS factors up to 8, with deviation increasing at CS factors > 8. Subcortical structures produced less consistent measurements than cortical parcellations at higher CS factors. RF shimming using full slice coverage 2D dual refocusing echo acquisition mode (DREAM) and full coverage 3D dual TR approaches further improved measurement precision. BFFE is a more optimal sequence than TSE for phase-based MREPT in brain. Depending on the area of the brain being measured, the scan can be safely accelerated with compressed SENSE without sacrifice of precision, offering the potential to employ MREPT in clinical research and applications. RF shimming with better field mapping further improves precision of the conductivity measures

    A qualitative exploration of mental health services provided in community pharmacies.

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    The burden of mental health problems continues to grow worldwide. Community pharmacists', as part of the primary care team, optimise care for people living with mental illness. This study aims to examine the factors that support or hinder the delivery of mental health services delivered in Australian community pharmacies and proposes ideas for improvement. A qualitative study was conducted comprising focus groups with community pharmacists and pharmacy staff across metropolitan, regional, and rural areas of New South Wales, Australia. Data were collected in eight focus groups between December 2020 and June 2021. Qualitative data were analysed using thematic analysis. Thirty-three community pharmacists and pharmacy staff participated in an initial round of focus groups. Eleven community pharmacists and pharmacy staff participated in a second round of focus groups. Twenty-four factors that enable or hinder the delivery of mental health services in community pharmacy were identified. Participant's perception of a lack of recognition and integration of community pharmacy within primary care were identified as major barriers, in addition to consumers' stigma and lack of awareness regarding service offering. Suggestions for improvement to mental health care delivery in community pharmacy included standardised practice through the use of protocols, remuneration and public awareness. A framework detailing the factors moderating pharmacists, pharmacy staff and consumers' empowerment in mental health care delivery in community pharmacy is proposed. This study has highlighted that policy and funding support for mental health services is needed that complement and expand integrated models, promote access to services led by or are conducted in collaboration with pharmacists and recognise the professional contribution and competencies of community pharmacists in mental health care. The framework proposed may be a step to strengthening mental health support delivered in community pharmacies

    Plasma-Induced Frequency Chirp of Intense Femtosecond Lasers and Its Role in Shaping High-Order Harmonic Spectral Lines

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    We investigate the self-phase modulation of intense femtosecond laser pulses propagating in an ionizing gas and its effects on collective properties of high-order harmonics generated in the medium. Plasmas produced in the medium are shown to induce a positive frequency chirp on the leading edge of the propagating laser pulse, which subsequently drives high harmonics to become positively chirped. In certain parameter regimes, the plasma-induced positive chirp can help to generate sharply peaked high harmonics, by compensating for the dynamically-induced negative chirp that is caused by the steep intensity profile of intense short laser pulses.Comment: 5 pages, 5 figure

    Combining shock barometry with numerical modeling: insights into complex crater formation – The example of the Siljan impact structure (Sweden)

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    Siljan, central Sweden, is the largest known impact structure in Europe. It was formed at about 380 Ma, in the late Devonian period. The structure has been heavily eroded to a level originally located underneath the crater floor, and to date, important questions about the original size and morphology of Siljan remain unanswered. Here we present the results of a shock barometry study of quartz-bearing surface and drill core samples combined with numerical modeling using iSALE. The investigated 13 bedrock granitoid samples show that the recorded shock pressure decreases with increasing depth from 15 to 20 GPa near the (present) surface, to 10–15 GPa at 600 m depth. A best-fit model that is consistent with observational constraints relating to the present size of the structure, the location of the downfaulted sediments, and the observed surface and vertical shock barometry profiles is presented. The best-fit model results in a final crater (rim-to-rim) diameter of ~65 km. According to our simulations, the original Siljan impact structure would have been a peak-ring crater. Siljan was formed in a mixed target of Paleozoic sedimentary rocks overlaying crystalline basement. Our modeling suggests that, at the time of impact, the sedimentary sequence was approximately 3 km thick. Since then, there has been around 4 km of erosion of the structure

    Health Care Delivery Practices in Huntington's Disease Specialty Clinics : An International Survey

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    The CHDI Foundation, Inc. funds Enroll-HD and the activities of the Enroll-HD Care Improvement Committee, including the present survey. We would like to acknowledge the Enroll-HD and REGISTRY administrative staff that assisted in the recruitment of sites and sites that completed the survey.Peer reviewedPublisher PD

    Mitotic Defects Lead to Pervasive Aneuploidy and Accompany Loss of RB1 Activity in Mouse LmnaDhe Dermal Fibroblasts

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    Lamin A (LMNA) is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350) and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670). Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1) activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood.We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (Lmna(Dhe)). We found that dermal fibroblasts from heterozygous Lmna(Dhe) (Lmna(Dhe/+)) mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, Lmna(Dhe/+) fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3), a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1) also was perturbed in Lmna(Dhe/+) cells. Lmna(Dhe/+) fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects.These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control
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