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An anion doped aluminium chlorofluoride AlCl0.1F2.8(OTeF5)0.1 (ACF-teflate) was synthesized. The material contains pentafluoroorthotellurate (teflate) groups, which mimic fluoride ions electronically, but are sterically more demanding. They are embedded into the amorphous structure. The latter was studied by PDF analysis, EXAFS data and MAS NMR spectroscopy. The mesoporous powder is a Lewis superacid, and ATR-IR spectra of adsorbed CD3CN reveal a blue-shift of the adsorption band by 73 cm1, which is larger than the shift for SbF5. Remarkably, ACF-teflate catalyzes dehydrofluorination reactions of monofluoroalkanes to yield olefins in C6D6. In these cases, no Friedel-Crafts products were formed.

A potential role of dietary factors on the risk of ovarian cancer (OVC) has been suggested by ecologic studies due to observed differences in international incidence rates ([1][1]). The contribution of dietary factors to the etiology of OVC has been suggested through the modulation of the endogenous

GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low k cat values for carbapenems. Twenty-two GES variants have been discovered thus far, differing from each other by 1 to 3 amino acid substitutions that affect substrate specificity. GES-11 possesses a Gly243Ala substitution which seems to confer to this variant an increased activity against aztreonam and ceftazidime. GES-12 differs from GES-11 by a single Thr237Ala substitution, while GES-14 differs from GES-11 by the Gly170Ser mutation, which is known to confer increased carbapenemase activity. GES-11 and GES-12 were kinetically characterized and compared to GES-1 and GES-14. Purified GES-11 and GES-12 showed strong activities against most tested β-lactams, with the exception of temocillin, cefoxitin, and carbapenems. Both variants showed a significantly increased rate of hydrolysis of cefotaxime, ceftazidime, and aztreonam. On the other hand, GES-11 and GES-12 (and GES-14) variants all containing Ala243 exhibited increased susceptibility to classical inhibitors. The crystallographic structures of the GES-11 and GES-14 β-lactamases were solved. The overall structures of GES-11 and GES-14 are similar to that of GES-1. The Gly243Ala substitution caused only subtle local rearrangements, notably in the typical carbapenemase disulfide bond. The active sites of GES-14 and GES-11 are very similar, with the Gly170Ser substitution leading only to the formation of additional hydrogen bonds of the Ser residue with hydrolytic water and the Glu166 residue.

A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

We report the first description of the metallo-β-lactamase VIM-31, a new variant of VIM-2 with Tyr224His and His252Arg mutations, in Enterobacter cloacae 11236, which was isolated from blood specimens of a patient with colonic adenocarcinoma in Belgium. bla VIM-31 was found on a class 1 integron located on a self-transferable but not typeable 42-kb plasmid. Compared to values published elsewhere for VIM-2, the purified VIM-31 enzyme showed weaker catalytic efficiency against all the tested beta-lactam agents (except for ertapenem), resulting from lower k cat (except for ertapenem) and higher K m values for VIM-31.

The CphAII protein from the hyperthermophile Aquifex aeolicus shows the five conserved motifs of the metallo-β-lactamase (MBL) superfamily and presents 28% identity with the Aeromonas hydrophila subclass B2 CphA MBL. The gene encoding CphAII was amplified by PCR from the A. aeolicus genomic DNA and overexpressed in Escherichia coli using a pLex-based expression system. The recombinant CphAII protein was purified by a combination of heating (to denature E. coli proteins) and two steps of immobilized metal affinity chromatography. The purified enzyme preparation did not exhibit a β-lactamase activity but showed a metal-dependent phosphodiesterase activity versus bis-p-nitrophenyl phosphate and thymidine 5'-monophosphate p-nitrophenyl ester, with an optimum at 85°C. The circular dichroism spectrum was in agreement with the percentage of secondary structures characteristic of the MBL αββα fold.

Background Finite mixture models posit the existence of a latent categorical variable and can be used for probabilistic classification. The authors illustrate the use of mixture models for dietary pattern analysis. An advantage of this approach is taking classification uncertainty into account. Methods Participants were a random sample of women from the European Prospective Investigation into Cancer. Food consumption was measured using dietary questionnaires. Mixture models identified latent classes in food consumption data, which were interpreted as dietary patterns. Results Among various assumptions examined, models allowing the variance of foods to vary within and between classes fit better than alternatives assuming constant variance (the K-means method of cluster analysis also makes the latter assumption). An eight-class model was best fitting and five patterns validated well in a second random sample. Patterns with lower classification uncertainty tended to be better validated. One pattern showed low consumption of foods despite being associated with moderate body mass index. Conclusion Mixture modelling for dietary pattern analysis has advantages over both factor and cluster analysis. In contrast to these other methods, it is easy to estimate pattern prevalence, to describe patterns and to use patterns to predict disease taking classification uncertainty into account. Owing to substantial error in food consumptions, any analysis will usually find some patterns that cannot be well validated. While knowledge of classification uncertainty may aid pattern evaluation, any method will better identify patterns from food consumptions measured with less error. Mixture models may be useful to identify individuals who under-report food consumption.

The metallo-β-lactamase (MBL) GOB-1 was expressed via a T7 expression system in Escherichia coli BL21(DE3). The MBL was purified to homogeneity and shown to exhibit a broad substrate profile, hydrolyzing all the tested β-lactam compounds efficiently. The GOB enzymes are unique among MBLs due to the presence of a glutamine residue at position 116, a zinc-binding residue in all known class B1 and B3 MBL structures. Here we produced and studied the Q116A, Q116N and Q116H mutants. The substrate profiles were similar for each mutant, but with significantly reduced activity compared with that of the wild-type. In contrast to the Q116H enzyme, which bound two zinc ions just like the wild-type, only one zinc ion is present in Q116A and Q116N. These results suggest that the Q116 residue plays a role in the binding of the zinc ion in the QHH site.

OBJECTIVE: To identify combinations of food groups that explain as much variation in absolute intakes of 23 key nutrients and food components as possible within the country-specific populations of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: The analysis covered single 24-h dietary recalls (24-HDR) from 36,034 subjects (13,025 men and 23,009 women), aged 35-74 years, from all 10 countries participating in the EPIC study. In a set of 39 food groups, reduced rank regression (RRR) was used to identify those combinations (RRR factors) that explain the largest proportion of variation in intake of 23 key nutrients and food components, namely, proteins, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, sugars (sum of mono- and disaccharides), starch, fibre, alcohol, calcium, iron, potassium, phosphorus, magnesium, vitamin D, beta-carotene, retinol and vitamins E, B1, B2, B6, B12 and C (RRR responses). Analyses were performed at the country level and for all countries combined. RESULTS: In the country-specific analyses, the first RRR factor explained a considerable proportion of the total nutrient intake variation in all 10 countries (27.4-37.1%). The subsequent RRR factors were much less important in explaining the variation (

Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet–cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15 351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6·0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2·00; 95 % CI 1·30, 3·09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.

BACKGROUND: International multicentre studies on diet and cancer are relatively new in epidemiological research. They offer a series of challenging methodological issues for the evaluation of the association between dietary exposure and disease outcomes, which can both be quite heterogeneous across different geographical regions. This requires considerable work to standardize dietary measurements at the food and the nutrient levels. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a calibration study was set up to express individual dietary intakes according to the same reference scale. A linear regression calibration model was used to correct the association between diet and disease for measurement errors in dietary exposures. In the present work, we describe an approach for analysing the EPIC data, using as an example the evaluation of the association between fish intake and colorectal cancer incidence. RESULTS: Sex- and country-specific attenuation factors ranged from 0.083 to 0.784, with values overall higher for men compared with women. Hazard ratio estimates of colorectal cancer for a 10 g/day increase in fish intake were 0.97 [95% confidence interval (CI): 0.95-0.99] and 0.93 (0.88-0.98), before and after calibration, respectively. CONCLUSIONS: In a multicentre study, the diet/disease association can be evaluated by exploiting the whole variability of intake over the entire study. Calibration may reduce between-centre heterogeneity in the diet-disease relationship caused by differential impact of measurement errors across cohorts. Udgivelsesdato: 2008-Apr

For epidemiological studies, a simple semiquantitative FFQ was developed to assess the frequency of intake of food items demonstrated with graphically displayed portion sizes. As a validation study, a random sample of 393 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study completed 2 unannounced 24-h dietary recalls (24HDR) and the FFQ during 1 y. To calculate food and nutrient intakes, we compared the use of fitted portion sizes with the use of predefined portion sizes. Fitted portion sizes were calculated by summing food intakes over the 2 24HDR and dividing the sum by the frequency of intake reported in the FFQ for each FFQ food item, leading to similar mean intakes for FFQ and 24HDR. As predefined portion sizes, amounts that had been used in previous dietary assessments in EPIC-Potsdam were used. Mean intake of 12 food groups was 102% for men or women with fitted portion sizes and 79% for men and 95% for women with predefined portion sizes of intake measured with 2 24HDR. However, deattenuated, energy-adjusted correlation coefficients between FFQ and 24HDR were not better for 19 nutrients by the use of fitted portion sizes, with a mean correlation coefficient of 0.53 for men and 0.56 for women. Mean correlation coefficients for food groups also were similar for fitted and predefined portion sizes. Fitting portion sizes using recent reference data from a random sample of study participants improved the quantitative assessment of food and nutrient intake, but not ranking of study participants, compared with predefining portion sizes based on prior knowledge.

Background and Purpose— Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phophate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort. Methods— Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0±1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia. Results— Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia. Conclusions— Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.

Background Previous studies have shown dose-dependent and time-dependent effects of cigarette smoking and smoking cessation on C-reactive protein (CRP) concentrations in men, but results were inconsistent for women. The aim of this study was to evaluate the dose-dependent and time-dependent association of smoking and smoking cessation with CRP concentrations in men and women using a novel comprehensive smoking index (CSI). Design Cross-sectional study of representative US survey data (National Health and Nutrition Examination Survey 1999-2002). Methods The CSI simultaneously accounts for intensity, duration and time since cessation of smoking. We analyzed data of 3505 men and 3896 women using sex-specific multiple linear regression models adjusting for other determinants of CRP concentrations, including age, race/ethnicity, body mass index, alcohol intake, diabetes, physical activity, oral hormone use among women, and history of coronary heart disease, stroke, chronic obstructive pulmonary disease and arthritis. Results A positive association of similar strength was found between smoking and CRP concentrations in both men and women who did not use exogenous oral hormones. Among women who used exogenous oral hormones, no association with smoking was found. In older men and women it took several years after smoking cessation for CRP concentrations to return to that of individuals who never smoked. Conclusion Smoking is associated with dose-dependent and time-dependent increases in CRP concentrations in both men and women. Furthermore, the effect of exogenous oral hormones on CRP concentrations in women is affected by smoking in a dose-dependent fashion. Eur J Cardiovasc Prev Rehabil14:694-700 © 2007 The European Society of Cardiology

OBJECTIVE—We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations. RESEARCH DESIGN AND METHODS—A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35–65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score. Data from the EPIC-Heidelberg, the Tübingen Family Study for Type 2 Diabetes (TÜF), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score. RESULTS—Information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118–983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were −0.56 in the TÜF and −0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TÜF and 0.75 in the MeSyBePo studies. CONCLUSIONS—The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes.

The metallo-β-lactamase VIM-31 differs from VIM-2 by only two Tyr224His and His252Arg substitutions. Located close to the active site, the Tyr224His substitution is also present in VIM-1, VIM-4, VIM-7 and VIM-12. The VIM-31 variant was reported in 2012 from Enterobacter cloacae and kinetically characterized. It exhibits globally lower catalytic efficiencies than VIM-2. In the present study, we report the three-dimensional structures of VIM-31 in its native (reduced) and oxidized forms. The so-called 'flapping-loop' (loop 1) and loop 3 of VIM-31 were not positioned as in VIM-2 but instead were closer to the active site as in VIM-4, resulting in a narrower active site in VIM-31. Also, the presence of His224 in VIM-31 disrupts hydrogen-bonding networks close to the active site. Moreover, a third zinc-binding site, which also exists in VIM-2 structures, could be identified as a structural explanation for the decreased activity of VIM-MBLs at high zinc concentrations.

Aims/hypothesis The aim of this study was to prospectively examine the association between body iron stores and risk of type 2 diabetes. Methods We designed a case–cohort study among 27,548 individuals within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. During 7 years of follow-up, 849 incident cases of type 2 diabetes were identified. Of these, 607 remained for analyses after exclusion of participants with missing data or abnormal glucose levels at baseline. A sub-cohort of 2,500 individuals was randomly selected from the full cohort, comprising 1,969 individuals after applying the same exclusion criteria. Results After adjustment for age, sex, BMI, waist circumference, sports activity, bicycling, education, occupational activity, smoking habit, alcohol consumption and circulating levels of γ-glutamyltransferase, alanine aminotransferase, fetuin-A, high-sensitivity C-reactive protein, adiponectin, HDL-cholesterol and triacylglycerol, higher serum ferritin concentrations were associated with a higher risk of type 2 diabetes (RR in the highest vs lowest quintile, 1.73; 95% CI 1.15, 2.61; ptrend00.002). No significant association was observed for soluble transferrin receptor (RR 1.33; 95% CI 0.85, 2.09; ptrend00.50). The soluble transferrin receptor-toferritin ratio was significantly inversely related to risk (RR 0.61; 95% CI 0.41, 0.91; ptrend00.02). Conclusions/interpretation High ferritinlevelsare associated with higher risk of type 2 diabetes independently of established diabetes risk factors and a range of diabetes biomarkers whereas soluble transferrin receptor concentrations are not related torisk. These results support the hypothesisthathigher iron stores below the level of haemochromatosis are associated with risk of type 2 diabetes.

Objective: Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR. Design: In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR). Results: Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR. Conclusions: The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.

Disease can be caused by different mechanisms. A possible causal model proposed by Rothman is a complete causal mechanism or a so-called "sufficient cause" consisting of a set of component causes that can be illustrated in a pie chart. However, this model does not allow finding out what sufficient causes produce the majority of cases. The authors' objective was to extend Rothman's work by quantifying the proportion of disease that can be attributed to a class of sufficient causes. The underlying idea was to consider all combinations of a given set of known risk factors and to assign each combination to a class of sufficient causes. This assignment makes it possible to evaluate a class of sufficient causes by the population attributable fraction of the corresponding combination of risk factors. The approach presented was applied to sufficient causes of myocardial infarction by use of data on participants recruited between 1994 and 1998 into the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. As a result, 51.8% of cases were attributed to only four different classes of sufficient causes. In conclusion, the statistical method described in the paper may be beneficial for quantifying the importance of different sufficient causes and for improving the efficiency of public health programs.

Background Inflammation is considered a key mechanism leading to type 2 diabetes, but dietary exposures that lead to inflammation and diabetes are largely unknown.

The aim of the study was to identify a dietary pattern predictive of subsequent annual weight change by using dietary composition information. Study subjects were 24,958 middle-aged men and women of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. To derive dietary patterns, we used the reduced rank regression method with 3 response variables presumed to affect weight change: fat density, carbohydrate density, and fiber density. Annual weight change was computed by fitting a linear regression line to each person's body weight data (baseline, and 2- and 4-y follow-up) and determining the slope. In linear regression models, the pattern score was related to annual weight change. We identified a food pattern of high consumption of whole-grain bread, fruits, fruit juices, grain flakes/cereals, and raw vegetables, and of low consumption of processed meat, butter, high-fat cheese, margarine, and meat to be predictive of subsequent weight change. Mean annual weight gain gradually decreased with increasing pattern score (P for trend < 0.0001), i.e., subjects scoring high for the pattern maintained their weight or gained significantly less weight over time compared with subjects with an opposite pattern. However, the prediction of annual weight change by the food pattern was significant only in nonobese subjects. In this study population, we identified a food pattern characterized by high-fiber and low-fat food choices that can help to maintain body weight or at least prevent excess body weight gain.

Uteroglobin (UG) is a conserved protein which is induced by progesterone and secreted by the epithelia of various mammalian reproductive and respiratory organs. Recombinant bovine uteroglobin (recbUG), consisting of 80 amino acids with a C-terminal His6 tag, was overexpressed in Escherichia coli and purified. The protein was crystallized in two geometric forms, rhomboid and cuneate (wedge-shaped), by the hanging-drop vapour-diffusion method at 295 K. The rhomboid crystals diffracted to a maximum resolution of 1.6 A using synchrotron radiation. These crystals belong to space group P2(1)2(1)2, with unit-cell parameters a = 81.42, b = 82.82, c = 45.26 A, and contain four monomers per asymmetric unit. The cuneate crystals diffracted to 2.35 A resolution using a rotating-anode generator. These crystals belong to space group C222(1), with unit-cell parameters a = 43.39, b = 93.94, c = 77.30 A, and contain two molecules per asymmetric unit.

We report the discovery of a family of organic compounds, substituted 1,3,5-benzenetrisamides, thatdepending on subtle details of their chemical structureare capable of selectively and extremely efficiently nucleating the growth of the common α-crystal modification of the major industrial polymer isotactic polypropylene (i-PP), rendering this normally turbid material highly transparent (“clarified”) at exceedingly low concentrations (as low as a weight fraction of 0.0002), inducing the mechanically distinct, tough i-PP β-polymorph, or promoting growth of hybrids of both crystallographic modifications with heretofore unknown combinations of the above desirable optical-mechanical properties. In addition, these trisamide-based compounds exhibit excellent thermal stability and do not feature absorption of visible light, adding to a most favorable set of characteristics that provides marked benefits over the presently employed nucleating/clarifying agents.

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.

Increased levels of IL-6 add further risk to the impact of obesity in respect to the development of type 2 diabetes mellitus (T2DM). A C-174G polymorphism within the IL-6 promoter region was shown to influence transcription rate of IL-6. We made use of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort of 27,548 individuals, selecting 188 T2DM cases and 376 controls to investigate this polymorphism in respect to development of T2DM. This polymorphism was found to modify the correlation between body mass index (BMI) and IL-6 by showing a much stronger increase of IL-6 at increased BMI for CC genotypes compared with GG genotypes. Interestingly, C-174G polymorphism was found to be an effect modifier for the impact of BMI regarding T2DM. Whereas BMI greater than or equal to 28 kg/m2 increased the risk of T2DM 3.44-fold [95% confidence interval (CI), 1.34- to 8.24-fold] for GG genotypes and 2.94-fold (95% CI, 1.56- to 5.56-fold) for GC genotypes, we found a 17.68-fold (95% CI, 3.57- to 87.66-fold) increase in risk for CC genotypes. In conclusion, obese individuals with BMI greater than or equal to 28 kg/m2 carrying the CC genotype showed a more than 5-fold increased risk of developing T2DM compared with the remaining genotypes and, hence, might profit most from weight reduction.

Analysis of dietary patterns is considered a useful approach to the examination of diet-disease associations. This study examined the risk of incident hypertension associated with dietary patterns in 8,552 women in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam Study. The baseline examination was carried out between 1994 and 1998. During 2-4 years of follow-up (through May 15, 2002), 123 incident hypertension cases were verified by medical records. Two exploratory dietary patterns, a "traditional cooking" pattern (meat, cooked vegetables, sauce, potatoes, and poultry) and a "fruits and vegetables" pattern (fruits, raw vegetables, and vegetable oil), were identified by exploratory factor analysis and confirmed by confirmatory factor analysis. Additionally, a hypothesis-oriented pattern based on the Dietary Approaches to Stop Hypertension (DASH) Study was defined (fruits, vegetables, and milk products). Patterns' associations with disease risk were estimated by Cox regression. While no significant associations were observed for the traditional cooking pattern or the fruits and vegetables pattern after adjustment for potential confounders, women in the third quartile of the DASH pattern were at lower risk than women in the lowest quartile (hazard rate ratio = 0.51, 95% confidence interval: 0.29, 0.89). These results suggest that this hypothesis-oriented pattern might play an important role in the risk of hypertension.

Purpose: To compare history of 22 different diseases reported during an in-person interview with that reported on a mailed self-administered questionnaire. Methods: 7841 participants of the European Prospective Investigation into Cancer (EPIC)-Potsdam study. The interview at baseline and the questionnaire at follow-up approximately 2 years later included identical questions about whether the participant had ever had a physician diagnosis of each disease. Incident diagnoses occurring in the interval between the interview and questionnaire were excluded from the analysis. Results: Agreement between self-report from the interview and from the questionnaire was highest (κ=0.83–0.88) for myocardial infarction, cancer and diabetes mellitus; it was lower (κ=0.68–0.77) for gout, hypertension, hay fever, asthma, osteoporosis, ulcer of the duodenum, thyroid disease, stroke, and kidney stones, and was lowest (κ=0.39–0.59) for chronic gastritis, ulcer of the stomach, cerebral ischemia, benign tumor, inflammatory bowel disease, angina pectoris, hyperlipidemia, rheumatism, colon polyps and skin disease. The poor agreement for less severe or more transient diseases was primarily a result of disease frequently being reported at the interview but not on the questionnaire. Conclusion: Self-administered questionnaires do not generate same information particularly for less severe or transient diseases as personal interviews. For these diseases, self-administered questionnaires are not recommended. Pilot studies that test validity will be necessary.

A subclinical inflammatory reaction has been shown to precede the onset of type 2 (non-insulin-dependent) diabetes. We therefore examined prospectively the effects of the central inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) on the development of type 2 diabetes. We designed a nested case-control study within the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study including 27,548 individuals. Case subjects were defined to be those who were free of type 2 diabetes at baseline and subsequently developed type 2 diabetes during a 2.3-year follow-up period. A total of 192 cases of incident type 2 diabetes were identified and matched with 384 non-disease-developing control subjects. IL-6 and TNF-alpha levels were found to be elevated in participants with incident type 2 diabetes, whereas IL-1beta plasma levels did not differ between the groups. Analysis of single cytokines revealed IL-6 as an independent predictor of type 2 diabetes after adjustment for age, sex, BMI, waist-to-hip ratio (WHR), sports, smoking status, educational attainment, alcohol consumption, and HbA(1c) (4th vs. the 1st quartile: odds ratio [OR] 2.6, 95% CI 1.2-5.5). The association between TNF-alpha and future type 2 diabetes was no longer significant after adjustment for BMI or WHR. Interestingly, combined analysis of the cytokines revealed a significant interaction between IL-1beta and IL-6. In the fully adjusted model, participants with detectable levels of IL-1beta and elevated levels of IL-6 had an independently increased risk to develop type 2 diabetes (3.3, 1.7-6.8), whereas individuals with increased concentrations of IL-6 but undetectable levels of IL-1beta had no significantly increased risk, both compared with the low-level reference group. These results were confirmed in an analysis including only individuals with HbA(1c)

A remelting-restabilization technique was applied for the recycling of post-used, yellow pigmented high density polyethylene (HDPE) bottle crates. In order to evaluate the potential of the recyclate to be used in the original apllication, the most important parameters were investigated: processing stability, long-term heat stability and light stability. A multiple extrusion cycles procedure at different reprocessing temperatures was performed for monitoring the processing stability of the restabilized and non-restabilized material. Oven aging was applied for about 8000 h (i.e., more than one year) to evaluate the long term thermal stability of the crate material, as manifested by melt flow rate, tensile impact strength, and time until embrittlement measurements. To evaluate the light stability of the recycled material artificial weathering was applied for about 8000 h, whereas the tensile impact strength was monitored. The latter data were enriched with microphotographs of the specimens surface. Finnaly, repigmentation was used to investigate the role of new pigments on the final performance of the recyled product. The results illustrate that restabilization is mandatory for the quality improvement of post-used crates ensuring its re-use in the original application and thus making closed loop recycling.

Nucleic acids research 43(20), 9680-9693 (2015). doi:10.1093/nar/gkv1056, Published by Information Retrieval Ltd., London

Objective: To evaluate the influence of recent weight changes (weight gain, loss and cycling) on subsequent weight changes. Design: Prospective cohort study with 2 y of follow-up. Data analysis with a polytomous logistic regression model. Subjects: A total of 18 001 non-smoking subjects, 6689 men and 11 312 women, from the general population. Measurements: Body height and weight measurements and interview data on lifestyle habits and medical history at baseline. For follow-up, self-administered questionnaires for assessment of body weight and incident diseases. Results: Recent changes in body weight, that is weight gain, weight loss and weight cycling, were significant predictors of subsequent weight changes in both men and women after controlling for age, baseline BMI and several lifestyle and behavioural characteristics as potential confounding factors. Weight cycling before baseline was the strongest predictor of subsequent large weight gain (≥2 kg) with an odds ratio (OR) of 4.84 (95% confidence interval (CI) 3.34–7.02) in men. In women, prior weight loss was the strongest predictor of subsequent large weight gain (OR 4.77; 95% CI 3.63–6.03), followed by weight cycling (OR 3.02; 95% CI 2.15–4.25). Conclusion: These data indicate the need for thorough weight history assessment to identify those who are most likely to gain weight. Effective weight control before the development of obesity or after intentional weight loss due to obesity should be a primary goal in the management of obesity.

CYP154C5 fromNocardia farcinicais a bacterial cytochrome P450 monooxygenase active on steroid molecules. The enzyme has recently been shown to exhibit exclusive regioselectivity and stereoselectivity in the conversion of various pregnans and androstans, yielding 16α-hydroxylated steroid products. This makes the enzyme an attractive candidate for industrial application in steroid hormone synthesis. Here, crystal structures of CYP154C5 in complex with four different steroid molecules were solved at resolutions of up to 1.9 Å. These are the first reported P450 structures from the CYP154 family in complex with a substrate. The active site of CYP154C5 forms a flattened hydrophobic channel with two opposing polar regions, perfectly resembling the size and polarity distribution of the steroids and thus resulting in highly specific steroid binding withKdvalues in the range 10–100 nM. Key enzyme–substrate interactions were identified that accounted for the exclusive regioselectivity and stereoselectivity of the enzyme. Additionally, comparison of the four CYP154C5–steroid structures revealed distinct structural differences, explaining the observed variations in kinetic data obtained for this P450 with the steroids pregnenolone, dehydroepiandrosterone, progesterone, androstenedione, testosterone and nandrolone. This will facilitate the generation of variants with improved activity or altered selectivity in the future by means of protein engineering.

Nucleating agents are used in semi-crystalline polymer systems (mainly polyolefins) to increase the rate of crystallization. These agents increase degree of crystallinity and lamellae thickness and, hence, improve stiffness and strength. In addition to altered mechanical characteristics, clarifying agents do also improve optical properties. This paper provides a brief overview on nucleating / clarifying agents. The efficiency of such products (e.g. Na-benzoate, sorbitol acetals) for polypropylene (PP homopolymer, PP copolymer) is evaluated. The clarifiers Irgaclear D ((1,3:2,4))-dibenzylidene sorbitol) and Irgaclear DM (1,3:2,4-Bis-(p-methylbenzylidene) sorbitol) provide a 3-dimensional fibrillar structure upon cooling from the polymer melt. This magnified nucleation density yields spherulites with reduced size (< 1micron) - in comparison to non-nucleated products. Addition of Irgaclear to polypropylene leads to increased clarity, reduced haze and enhanced stiffness of molded parts. Higher recrystallization temperatures results in shorter cycle times and increased throughput during the molding process.

Oven aging was applied for about 8800 hours (more than one year) to evaluate the long-term thermal stability of post-used HDPE material recycled from bottle crates. For recycling, the remelting-restabilization technique was applied. To study the effect of restabilization, crystallinity and melt flow rate were monitored during heat aging. Furthermore, tensile strength and tensile impact strength were followed together with the time until embrittlement. These data were enriched with microphotographs of the specimens' surfaces. Finally, repigmentation was used to evaluate the role of new pigments on the final performance of the recycled material. The results illustrate that restabilization is mandatory for improving the long-term thermal stability of the post-used crate material, enabling its reuse in the original application.

This paper presents an expository development of Stein estimation in several distribution families. Considered are both the point estimation and confidence interval cases. Specific results for linear regression models are added. Emphasis is laid on the chronological history and on recent results.

Artificial weathering was applied for about 8000 h to evaluate the light stability of postconsumer high-density polyethylene (HDPE) material recycled from bottle crates. For recycling the remelting-restabilization technique was applied. To study the effect of the restabilization, the tensile impact strength was monitored during the artificial weathering exposure. The data were compared with microphotographs of the specimens' surface. Repigmentation was used to evaluate the role of new pigments on the final performance of the recycled material. The repigmented grades were further studied by colorimetric determinations of the color difference (ΔE) during artificial weathering. The results illustrate that the restabilization is mandatory for improving the light stability of the postconsumer crate material, ensuring its re-use in the original application. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 1118–1127, 2000

A remelting–restabilization technique was applied for the recycling of postused, yellow-pigmented high-density polyethylene (HDPE) bottle crates. Multiple extrusion cycles procedure, at different reprocessing temperatures, was performed for monitoring the processing stability of the restabilized and nonrestabilized material as reference. In addition, mechanical properties measurements were carried out, to study further the effect of restabilization on the performance of the recycled material. Finally, repigmentation was used to investigate the role of new pigments on the final recycled product. The results illustrate that restabilization of postused crates leads to careful reprocessing without severe degradation, which is an essential prerequisite for reuse in the original application. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1775–1785, 1999