22,037 research outputs found

    Mechanism of T-Cell Lymphomagenesis: Transformation of Growth-Factor-Dependent T-Lymphoblastoma Cells to Growth-Factor-Independent T-Lymphoma Cells

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    In a previous paper we described the induction by x-irradiation or radiation-induced leukemia virus-in-oculation of two classes of lymphoid T-cell neoplasms: The first class, designated T-cell lymphoblastoma (TCLB), consists of growth-factor-dependent eudiploid cells that home to the spleen and give rise to splenic tumors on injection into syngeneic mice; the second class, designated T-cell lymphoma (TCL), consists of growth-factor-independent aneuploid or pseudodiploid cells that give rise to local tumors at the site of subcutaneous injection. This paper describes the generation of a family of growth-factor-independent aneuploid or pseudodiploid TCL cells after the injection into the thymus of growth-factor-dependent diploid TCLB cells. In contrast to the donor TCLB cells, the resulting TCL cells could be cloned in semisolid medium, produced local tumors at the site of subcutaneous injection, and proliferated in a growth-factor-independent fashion in vitro. The induced growth-factor-independent TCL cells were chromosomally and phenotypically unstable and continued to evolve both in vivo and in vitro. After propagation in the thymus, the cells often showed stable translocations in addition to the evolving aneuploidy. We propose that the chromosome abnormalities induced during the proliferation of growth-factor-dependent TCLB cells in the thymus constitute a general mechanism by which neoplastic cells progress from growth-factor dependency to independency

    Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes.

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    BACKGROUND: Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent. METHODS: Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child\u27s life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined. RESULTS: Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales). CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development

    Nonlinear ac response of anisotropic composites

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    When a suspension consisting of dielectric particles having nonlinear characteristics is subjected to a sinusoidal (ac) field, the electrical response will in general consist of ac fields at frequencies of the higher-order harmonics. These ac responses will also be anisotropic. In this work, a self-consistent formalism has been employed to compute the induced dipole moment for suspensions in which the suspended particles have nonlinear characteristics, in an attempt to investigate the anisotropy in the ac response. The results showed that the harmonics of the induced dipole moment and the local electric field are both increased as the anisotropy increases for the longitudinal field case, while the harmonics are decreased as the anisotropy increases for the transverse field case. These results are qualitatively understood with the spectral representation. Thus, by measuring the ac responses both parallel and perpendicular to the uniaxial anisotropic axis of the field-induced structures, it is possible to perform a real-time monitoring of the field-induced aggregation process.Comment: 14 pages and 4 eps figure

    Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future

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    Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients

    Children of prisoners: exploring the impact of families' reappraisal of the role and status of the imprisoned parent on children's coping strategies

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    Qualitative data from a larger study on the impact of parental imprisonment in four countries found that children of prisoners face fundamentally similar psychological and social challenges. The ways that children cope, however, are influenced by the interpretative frame adopted by the adults around them, and by how issues of parental imprisonment are talked about in their families. This article argues that families have to reappraise their view of the imprisoned parent and then decide on their policy for how to deal with this publicly. Their approach may be based on openness and honesty or may emphasise privacy and secrecy, or a combination of these. Children are likely to be influenced by their parents'/carers' views, although these may cause conflict for them. Where parents/carers retain a positive view of the imprisoned parent, children are likely to benefit; where parents/carers feel issues of shame and stigma acutely, this is likely to be transmitted to their children. This is important for social workers and practitioners involved in supporting prisoners' families and for parenting programmes

    Near-Infrared Polarimetric Adaptive Optics Observations of NGC 1068: A torus created by a hydromagnetic outflow wind

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    We present J' and K' imaging linear polarimetric adaptive optics observations of NGC 1068 using MMT-Pol on the 6.5-m MMT. These observations allow us to study the torus from a magnetohydrodynamical (MHD) framework. In a 0.5" (30 pc) aperture at K', we find that polarisation arising from the passage of radiation from the inner edge of the torus through magnetically aligned dust grains in the clumps is the dominant polarisation mechanism, with an intrinsic polarisation of 7.0%±\pm2.2%. This result yields a torus magnetic field strength in the range of 4-82 mG through paramagnetic alignment, and 13920+11^{+11}_{-20} mG through the Chandrasekhar-Fermi method. The measured position angle (P.A.) of polarisation at K' is found to be similar to the P.A. of the obscuring dusty component at few parsec scales using infrared interferometric techniques. We show that the constant component of the magnetic field is responsible for the alignment of the dust grains, and aligned with the torus axis onto the plane of the sky. Adopting this magnetic field configuration and the physical conditions of the clumps in the MHD outflow wind model, we estimate a mass outflow rate \le0.17 M_{\odot} yr1^{-1} at 0.4 pc from the central engine for those clumps showing near-infrared dichroism. The models used were able to create the torus in a timescale of \geq105^{5} yr with a rotational velocity of \leq1228 km s1^{-1} at 0.4 pc. We conclude that the evolution, morphology and kinematics of the torus in NGC 1068 can be explained within a MHD framework.Comment: 14 pages, 4 figures, Accepted by MNRA

    Dilute Birman--Wenzl--Murakami Algebra and Dn+1(2)D^{(2)}_{n+1} models

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    A ``dilute'' generalisation of the Birman--Wenzl--Murakami algebra is considered. It can be ``Baxterised'' to a solution of the Yang--Baxter algebra. The Dn+1(2)D^{(2)}_{n+1} vertex models are examples of corresponding solvable lattice models and can be regarded as the dilute version of the Bn(1)B^{(1)}_{n} vertex models.Comment: 11 page

    PolNet:A Tool to Quantify Network-Level Cell Polarity and Blood Flow in Vascular Remodeling

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    In this article, we present PolNet, an open-source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterize the hemodynamics of the vascular networks under study. The tool enables, to our knowledge for the first time, a network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarization and migration during vascular patterning, as demonstrated by two recent publications. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the Lesser General Public License
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