490 research outputs found
Information extraction and transmission techniques for spaceborne synthetic aperture radar images
Information extraction and transmission techniques for synthetic aperture radar (SAR) imagery were investigated. Four interrelated problems were addressed. An optimal tonal SAR image classification algorithm was developed and evaluated. A data compression technique was developed for SAR imagery which is simple and provides a 5:1 compression with acceptable image quality. An optimal textural edge detector was developed. Several SAR image enhancement algorithms have been proposed. The effectiveness of each algorithm was compared quantitatively
Perturbation Energy Production in Pipe Flow over a Range of Reynolds Numbers using Resolvent Analysis
The response of pipe flow to physically realistic, temporally and spatially continuous(periodic) forcing is investigated by decomposing the resolvent into orthogonal forcing and response pairs ranked according to their contribution to the resolvent 2-norm. Modelling the non-linear terms normally neglected by linearisation as unstructured forcing permits qualitative extrapolation of the resolvent norm results beyond infinitesimally small perturbations to the turbulent case. The concepts arising have a close relationship to input output transfer function analysis methods known in the control systems literature. The body forcings that yield highest disturbance energy gain are identified and ranked by the decomposition and a worst-case bound put on the energy gain integrated across the pipe cross-section. Analysis of the spectral variation of the corresponding response modes reveals interesting comparisons with recent observations of the behavior of the streamwise velocity in high Reynolds number (turbulent) pipe flow, including the importance of very long scales of the order of ten pipe radii, in the extraction of turbulent energy from the mean flow by the action of turbulent shear stress against the velocity gradient
Association of the tumour necrosis factor alpha -308 but not the interleukin 10 -627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology. Abnormalities in immune regulation and genetic associations suggest that PSC is an immune mediated disease. Several polymorphisms within the tumour necrosis factor α (TNF-α) and interleukin 10 (IL-10) promoter genes have been described which influence expression of these cytokines. This study examines the possible association between polymorphisms at the −308 and −627 positions in the TNF-α and IL-10 promoter genes, respectively, and susceptibility to PSC.
METHODS TNF-α −308 genotypes were studied by polymerase chain reaction (PCR) in 160 PSC patients from Norway and the UK compared with 145 ethnically matched controls. IL-10 −627 genotypes were studied by PCR in 90 PSC patients compared with 84 ethnically matched controls.
RESULTS A total of 16% of Norwegian PSC patients and 12% of British PSC patients were homozygous for the TNF2 allele compared with 3% and 6% of respective controls. The TNF2 allele was present in 60% of PSC patients versus 30% of controls (ORcombined data=3.2 (95% confidence intervals (CI) 1.8–4.5); pcorr=10−5). The association between the TNF2 allele and susceptibility to PSC was independent of the presence of concurrent inflammatory bowel disease (IBD) in the PSC patients; 61% of PSC patients without IBD had TNF2 compared with 30% of controls (ORcombined data=3.2 (95% CI 1.2–9.0); pcorr=0.006 ). There was no difference in the −627 IL-10 polymorphism distributions between patients and controls in either population. The increase in TNF2 allele in PSC patients only occurs in the presence of DRB1*0301 (DR3) and B8. In the combined population data, DRB1*0301 showed a stronger association with susceptibility to PSC than both the TNF2 and B8 alleles (ORcombined data=3.8, pcorr=10−6 v ORcombined data=3.2, pcorr=10−5 vORcombined data =3.41, pcorr=10−4, respectively).
CONCLUSIONS This study identified a significant association between possession of the TNF2 allele, a G→A substitution at position −308 in the TNF-α promoter, and susceptibility to PSC. This association was secondary to the association of PSC with the A1-B8-DRB1*0301-DQA1*0501-DQB1*0201 haplotype. No association was found between the IL-10 −627 promoter polymorphism and PSC
Statistical analysis of coherent structures in transitional pipe flow
Numerical and experimental studies of transitional pipe flow have shown the
prevalence of coherent flow structures that are dominated by downstream
vortices. They attract special attention because they contribute predominantly
to the increase of the Reynolds stresses in turbulent flow. In the present
study we introduce a convenient detector for these coherent states, calculate
the fraction of time the structures appear in the flow, and present a Markov
model for the transition between the structures. The fraction of states that
show vortical structures exceeds 24% for a Reynolds number of about Re=2200,
and it decreases to about 20% for Re=2500. The Markov model for the transition
between these states is in good agreement with the observed fraction of states,
and in reasonable agreement with the prediction for their persistence. It
provides insight into dominant qualitative changes of the flow when increasing
the Reynolds number.Comment: 11 pages, 26 (sub)figure
Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.
The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed
Primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect
Quasielastic 12C(e,e'p) Reaction at High Momentum Transfer
We measured the 12C(e,e'p) cross section as a function of missing energy in
parallel kinematics for (q,w) = (970 MeV/c, 330 MeV) and (990 MeV/c, 475 MeV).
At w=475 MeV, at the maximum of the quasielastic peak, there is a large
continuum (E_m > 50 MeV) cross section extending out to the deepest missing
energy measured, amounting to almost 50% of the measured cross section. The
ratio of data to DWIA calculation is 0.4 for both the p- and s-shells. At w=330
MeV, well below the maximum of the quasielastic peak, the continuum cross
section is much smaller and the ratio of data to DWIA calculation is 0.85 for
the p-shell and 1.0 for the s-shell. We infer that one or more mechanisms that
increase with transform some of the single-nucleon-knockout into
multinucleon knockout, decreasing the valence knockout cross section and
increasing the continuum cross section.Comment: 14 pages, 7 figures, Revtex (multicol, prc and aps styles), to appear
in Phys Rev
Grouping of endocrine disrupting chemicals for mixture risk assessment – Evidence from a rat study
Exposure to mixtures of endocrine disrupting chemicals may contribute to the rising incidence of hormone-related diseases in humans. Real-life mixtures are complex, comprised of chemicals with mixed modes of action, and essential knowledge is often lacking on how to group such chemicals into cumulative assessment groups, which is an essential prerequisite to conduct a chemical mixture risk assessment.
We investigated if mixtures of chemicals with diverse endocrine modes of action can cause mixture effects on hormone sensitive endpoints in developing and adult rat offspring after perinatal exposure. Wistar rats were exposed during pregnancy and lactation simultaneously to either bisphenol A and butylparaben (Emix), diethylhexyl phthalate and procymidone (Amix), or a mixture of all four substances (Totalmix). In male offspring, the anogenital distance was significantly reduced and nipple retention increased in animals exposed to Amix and Totalmix, and the mixture effects were well approximated by the dose addition model. The combination of Amix and Emix responded with more marked changes on these and other endocrine-sensitive endpoints than each binary mixture on its own. Sperm counts were reduced by all exposures. These experimental outcomes suggest that the grouping of chemicals for mixture risk assessment should be based on common health outcomes rather than only similar modes or mechanisms of action. Mechanistic-based approaches such as the concept of Adverse Outcome Pathway (AOP) can provide important guidance if both the information on shared target tissues and the information on shared mode/mechanism of action are taken into account.Danish Environmental Protection Agency, Denmar
Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals
Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause-effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman's reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause-effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.Peer reviewe
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