832 research outputs found
Hausdorff moments in an inverse problem for the heat equation: numerical experiment
In this paper we consider the inverse boundary problem for the heat equation Deltau(x, t) = rho(x)partial derivative(t)u(x, t) in a bounded domain Omega subset of R-2. We develop and test numerically an algorithm of an approximate reconstruction of the unknown p(x). This algorithm is based on the moments' method for the heat equation developed by Kawashita, Kurylev and Soga
Tissue-specific expression of a human Polymorphic Epithelial mucin (MUCI) in transgenic mice
The human MUC1 gene codes for the core protein of a mucin which is expressed by glandular epithelia and the carcinomas which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucin, which also contains epitopes recognized by T-cells from breast and pancreatic cancer patients. For evaluating the potential use of mucin-reactive antibodies and mucin-based immunogens in cancer patients, a mouse model, expressing the MUC1 gene product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely useful. To this end, we have developed transgenic mouse strains expressing the human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was established using a 40-kilobase fragment containing 4.5 kilobases of 5\u27 and 27 kilobases of 3\u27 flanking sequence. The TG18 strain was developed using a 10.6-kilobase SacII fragment from the 40-kilobase fragment; this fragment contained 1.6 kilobases of 5\u27 sequence and 1.9 kilobases of 3\u27 flanking sequence. Both strains showed tissue specificity of expression of the MUC1 gene, which was very similar to the profile of expression seen in human tissues. The antibody SM-3 is directed to a core protein epitope, which is selectively exposed in breast cancers and which shows a more restricted distribution on normal human tissues. It was established that the distribution of the SM-3 epitope of PEM in the tissues of the transgenic mice is similar to that seen in humans. The transgenic mouse strains described here should form the basis for the development of a preclinical model for the evaluation of PEM-based antigens and of antibodies directed to PEM in cancer therapy
Mg II h&k fine structure prominence modelling and the consequences for observations
Aims. Using 2D MgāÆII h[amp]k solar prominence modelling, our aim is to understand the formation of complex line profiles and how these are seen by the Interface Region Imaging Spectrograph (IRIS). Additionally, we see how the properties of these simulated observations are interpreted through the use of traditional 1D prominence modelling.
Methods. We used a cylindrical non-local thermodynamic equilibrium (NLTE) 2D complete redistribution (CRD) code to generate a set of cylindrical prominence strands, which we stacked behind each other to produce complex line profiles. Then, with the use of the point spread functions (PSFs) of IRIS, we were able to predict how IRIS would observe these line profiles. We then used the 1D NLTE code PROM in combination with the Cross Root Mean Square method (xRMS) to find the properties recovered by traditional 1D prominence modelling.
Results. Velocities of magnitude lower than 10 km sā1 are sufficient to produce asymmetries in the MgāÆII h[amp]k lines. However, convolution of these with the PSFs of IRIS obscures this detail and returns standard looking single peaks. By increasing the velocities by a factor of three, we recover asymmetric profiles even after this convolution. The properties recovered by xRMS appear adequate at first, but the line profiles chosen to fit these profiles do not satisfactorily represent the line profiles. This is likely due to the large line width of the simulated profiles.
Conclusions. Asymmetries can be introduced by multithread models with independent Doppler velocities. The large line width created by these models makes it difficult for traditional 1D forward modelling to find good matches. This may also demonstrate degeneracies in the solution recovered by single-species 1D modelling
Rotation and activity of pre-main-sequence stars
We present a study of rotation (vsini) and chromospheric activity (Halpha EW)
based on an extensive set of high-resolution optical spectra obtained with MIKE
on the 6.5m Magellan Clay telescope. Our targets are 74 F-M dwarfs in the young
stellar associations Eta Cha, TW Hydrae, Beta Pic, and Tuc-Hor, spanning ages
from 6 to 30 Myr. While the Halpha EW for most F and G stars are consistent
with pure photospheric absorption, most K and M stars show chromospheric
emission. By comparing Halpha EW in our sample to results in the literature, we
see a clear evolutionary sequence: Chromospheric activity declines steadily
from the T Tauri phase to the main sequence. Using activity as an age
indicator, we find a plausible age range for the Tuc-Hor association of 10-40
Myr. Between 5 and 30 Myr, we do not see evidence for rotational braking in the
total sample, thus angular momentum is conserved, in contrast to younger stars.
This difference indicates a change in the rotational regulation at 5-10 Myr,
possibly because disk braking cannot operate longer than typical disk
lifetimes, allowing the objects to spin up. The rotation-activity relation is
flat in our sample; in contrast to main-sequence stars, there is no linear
correlation for slow rotators. We argue that this is because young stars
generate their magnetic fields in a fundamentally different way from
main-sequence stars, and not just the result of a saturated solar-type dynamo.
By comparing our rotational velocities with published rotation periods for a
subset of stars, we determine ages of 13 (7-20) Myr and 9 (7-17} Myr for the
Eta Cha and TWA associations, respectively, consistent with previous estimates.
Thus we conclude that stellar radii from evolutionary models by Baraffe et al.
(1998) are in agreement with the observed radii within +-15%. (abridged)Comment: 40 pages, 8 figures, ApJ, in pres
Activation of protein kinase CĪ“ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1
Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis of \u3c 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans-differentiate into a number of cell types including duct cells, Ī² cells, hepatocytes and adipocytes. Knowledge of the molecular pathways that regulate this plasticity should provide insight into PDAC and CP. MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for complete acinar cell maturation. The goal of this study was to examine the plasticity of acinar cells that do not express MIST1 (Mist1 -/-). The fate of acinar cells from C57Bl6 or congenic Mist1 -/- mice expressing an acinar specific, tamoxifen-inducible Cre recombinase mated to Rosa26 reporter LacZ mice (Mist1CreERT/- R26r) was determined following culture in a three-dimensional collagen matrix. Mist1CreERT/- R26r acini showed increased acinar dedifferentiation, formation of ductal cysts and transient increases in PDX1 expression compared to wild-type acinar cells. Other progenitor cell markers, including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1-/- cultures. Analysis of protein kinase C (PKC) isoforms by western blot and immunofluorescence identified increased PKCĪµ accumulation and nuclear localization of PKCĪ“ that correlated with increased duct formation. Treatment with rottlerin, a PKCĪ“-specific inhibitor, but not the PKCĪµ-specific antagonist ĪµV1-2, reduced acinar dedifferentiation, progenitor gene expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue samples showed reduced MIST1 expression combined with increased nuclear PKCĪ“ accumulation. These results suggest that the loss of MIST1 is a common event during PDAC and CP and events that affect MIST1 function and expression may increase susceptibility to these pathologies. Copyright Ā© 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Solar prominence diagnostics and their associated estimated errors from 1D NLTE Mg II h&k modelling
Aims. We present further development of the rolling root mean square (rRMS) algorithm. These improvements consist of an increase in computational speed and an estimation of the uncertainty on the recovered diagnostics. This improved algorithm is named the cross root mean square (xRMS) algorithm.
Methods. We used the quantile method to recover the statistics of the line profiles in order to study the evolution of the prominence observed by IRIS on 1 October 2019. We then introduced the improvements to rRMS. These improvements greatly increased the computational speed, and this increase in speed allowed us to use a large model grid. Thus, we utilised a grid of 23 940 models to recover the thermodynamic diagnostics. We used the āgoodā (but not ābestā) fitting models to recover an estimate of the uncertainty on the recovered diagnostics.
Results. The maximum line-of-sight (LOS) velocities were found to be 70 km sā1. The line widths were mostly 0.4 Ć
, with the asymmetries of most pixels around zero. The central temperature of the prominence was found to range from 10 kK to 20 kK, with uncertainties of approximately Ā±5 to Ā±15 kK. The central pressure was around 0.2 dyn cmā2, with uncertainties of Ā±0.2 to Ā±0.3 dyn cmā2. The ionisation degree ranged from 1 to 1000, with uncertainties mostly in the range Ā±10 to Ā±100. The electron density was mostly 1010 cmā3, with uncertainties of mostly Ā±109.
Conclusions. The new xRMS algorithm finds an estimation of the errors of the recovered thermodynamic properties. To our knowledge, this is the first attempt at systematically determining the errors from forward modelling. The large range of errors found may hint at the degeneracies present when using a single ion and/or species from forward modelling. In the future, co-aligned observations of more than one ion and/or species should be used to attempt to constrain this problem
Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis
The best treatment options for binge-eating disorder are unclear
Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.
The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis
The North Staffordshire Osteoarthritis Project ā NorStOP: Prospective, 3-year study of the epidemiology and management of clinical osteoarthritis in a general population of older adults
BACKGROUND: The clinical syndrome of joint pain and stiffness in older people is the commonest cause of disability and health care consultation in this age group. Yet there have been few prospective studies of its course over time and its impact on personal and social life. We plan a cohort study in the general population aged 50 years and over to determine the course and prognosis of hand, hip, knee and foot pain, and the impact of these syndromes on participation levels and health care use. METHODS: All patients aged 50 years and over registered with 3 local general practices are to be recruited to a population-based cohort study through the use of a two-stage mailing process. Participants will initially complete a "Health Survey" questionnaire. This will collect information on several areas of life including socio-demographics, general health, physical function, participation, and bodily pain. Those who state that they have experienced any hand problem or any pain in their hands, hips, knees, or feet in the previous 12 months, and also give permission to be re-contacted, will be mailed a "Regional Pains Survey" questionnaire which collects detailed information on the four selected body regions (hand, hips, knees, feet). Follow-up data for the three-year period subsequent to cohort recruitment will be collected through two sources: i) general practice medical records and ii) repeat mailed survey
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