Induction of p53 Expression in Skin by Radiotherapy and UV Radiation: a Randomized Study

Background: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or γ-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. Methods: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided. Results: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (rs = .78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. Conclusions: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatiti

A Single Nucleotide Polymorphism within the Acetyl-Coenzyme A Carboxylase Beta Gene Is Associated with Proteinuria in Patients with Type 2 Diabetes

It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4×10−6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33–1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35×10−8, odds ratio = 1.61, 95% Cl: 1.35–1.91). Rs2268388 was also associated with type 2 diabetes–associated end-stage renal disease (ESRD) in European Americans (p = 6×10−4, odds ratio = 1.61, 95% Cl: 1.22–2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes

Induction of Recursive Transfer Rules

Transfer rules are used in bi-lingual translation systems for transferring a logical representation of a source language sentence into a logical representation of the corresponding target language sentence. This work studies induction of transfer rules from examples of corresponding pairs of source-target quasi logical formulae (QLFs). The main features of this problem are: i) more than one rule may need to be produced from a single example, ii) only positive examples are provided and iii) the produced hypothesis should be recursive. In an earlier study of this problem, a system was proposed in which hand-coded heuristics were employed for identifying non-recursive correspondences. In this work we study the case when non-recursive transfer rules have been given to the system instead of heuristics. Results from a preliminary experiment with English-French QLFs are presented, demonstrating that this information is sufficient for the generation of generally applicable rules that can be us..

Building the DeNOx System: Experience from a Real-World Application of Machine Learning

Hogdalenverket is a combined heating and power station located in Stockholm, Sweden. At Hogdalenverket, waste from Stockholm households is burned to produce heat and power for the Stockholm area. Hogdalenverket has been instructed by the Swedish National Environment Protection Board to reduce its emissions of nitrogen oxides (NO x ). One way to achieve such a reduction is by injecting ammonia (NH 3 ) into the combustion chamber. The optimal amount of ammonia is affected by factors such as the temperature at the place of injection and the presence of various substances in the flue gasses. Machine learning has been applied to produce control rules for the injection of ammonia. In this paper we present the experience gained from developing this control system. We describe and characterize the different steps involved in the development of the system. We also give a characterization of the domain and the learning problem together with a motivation for the choice of l..

Induction of Logic Programs by Exampleguided Unfolding

Resolution has been used as a specialisation operator in several approaches to top-down induction of logic programs. This operator allows the overly general hypothesis to be used as a declarative bias that restricts not only what predicate symbols can be used in produced hypotheses, but also how the predicates can be invoked. The two main strategies for topdown induction of logic programs, Covering and Divide-and-Conquer, are formalised using resolution as a specialisation operator, resulting in two strategies for performing example-guided unfolding. These strategies are compared both theoretically and experimentally. It is shown that the computational cost grows quadratically in the size of the example set for Covering, while it grows linearly for Divide-and-Conquer. This is also demonstrated by experiments, in which the amount ofwork performed by Covering is up to 30 times the amount ofwork performed by Divideand-Conquer. The theoretical analysis shows that the hypothesis space is larger for Covering, and thus more compact hypotheses may be found by this technique than by Divide-and-Conquer. However, it is shown that for each non-recursive hypothesis that can be produced by Covering, there is an equivalent hypothesis (w.r.t. the background predicates) that can be produced by Divide-and-Conquer. A major draw-back of Divide-and-Conquer, in contrast to Covering, is that it is not applicable to learning recursive de nitions. 1

Alloy degradation in a co-firing biomass CFB vortex finder application at 880 degrees C

Mechanisms of alloy degradation in a fireside N-S-O-C-H-Cl-Na-K atmosphere at 880 degrees C were elucidated using SEM-EDS, chemical equilibrium calculations, and XRD. Alloys 310S, 800H/HT, and 600 were studied after 0, 8000, and 16,000 h exposure in a boiler co-firing biomass waste. For 310S and 800H/HT it was shown that nitrogen formed internal Cr nitrides lowering the Cr activity and inhibiting internal alloy Cr permeation, and that NaCl and Na2SO4 reacted with Cr oxide to form chromate and to accelerate the S and the Cl pickup. Alloy 600 showed no nitride or major chromate formation.Bio4Energ

Automatic Keyword Extraction Using Domain Knowledge Anette

Documents can be assigned keywords by frequency analysis of the terms found in the document text, which arguably is the primary source of knowledge about the document itself. By including a hierarchically organised domain specific thesaurus as a second knowledge source the quality of such keywords was improved considerably, as measured by match to previously manually assigned keywords

Understanding adherence to therapeutic guidelines: a multilevel analysis of statin prescription in the Skaraborg Primary Care Database

In Skaraborg, Sweden, the economic responsibility for tax-financed prescription drug costs was transferred from the regional administrative level to the local level (health care centre; HCC) in 2003. The aim of this study was to investigate the impact of this decentralization of economic responsibility on adherence to guidelines for prescribing lipid-lowering drugs. Data from all 24 public HCCs in Skaraborg on prescriptions for lipid-lowering drugs during 2003 and 2005 were extracted from the Skaraborg Primary Care Database (SPCD). Multilevel regression analysis (MLRA) was used to disentangle the variances at different levels of data (patient, physician, HCC). The outcome variable on the patient level was the prescription of the recommended statin (yes/no). Sex and age of the patients and sex, age and occupational status of the physician were included as fixed effects. The variance was expressed as the median odds ratio (MOR). The prevalence of adherence to guidelines for the prescription of statins increased from 77% in 2003 to 84% in 2005. The MLRA showed that in 2003 the variance was equally distributed between the HCC and physician levels (MORHCC2003 = 1.89 vs. MORPHYSICIAN2003 = 1.88). The variance between physicians and between HCCs decreased considerably between 2003 and 2005. The inclusion of individual and physician characteristics did not explain any of the remaining variance. The decentralized budget appears to have increased adherence to guidelines and reduced inefficient variation in prescribing