Subcomponent self-assembly of circular helical Dy6_{6}(L)6_{6} and bipyramid Dy12_{12}(L)8_{8} architectures directed via second-order template effects

In situ metal-templated (hydrazone) condensation also called subcomponent self-assembly of 4,6-dihydrazino-pyrimidine, o-vanillin and dysprosium ions resulted in the formation of discrete hexa- or dodecanuclear metallosupramolecular Dy$_{6}$(L)$_{6}$ or Dy$_{12}$(L)$_{8}$ aggregates resulting from second-order template effects of the base and the lanthanide counterions used in these processes. XRD analysis revealed unique circular helical or tetragonal bipyramid architectures in which the bis(hydrazone) ligand L adopts different conformations and shows remarkable differences in its mode of metal coordination. While a molecule of trimethylamine acts as a secondary template that fills the void of the Dy$_{6}$(L)$_{6}$ assembly, sodium ions take on this role for the formation of heterobimetallic Dy$_{12}$(L)$_{8}$ by occupying vacant coordination sites, thus demonstrating that these processes can be steered in different directions upon subtle changes of reaction conditions. Furthermore, Dy$_{6}$(L)$_{6}$ shows an interesting spin-relaxation energy barrier of 435 K, which is amongst the largest values within multinuclear lanthanide single-molecular magnets

A Cauchy-Dirac delta function

The Dirac delta function has solid roots in 19th century work in Fourier analysis and singular integrals by Cauchy and others, anticipating Dirac's discovery by over a century, and illuminating the nature of Cauchy's infinitesimals and his infinitesimal definition of delta.Comment: 24 pages, 2 figures; Foundations of Science, 201

Ten Misconceptions from the History of Analysis and Their Debunking

The widespread idea that infinitesimals were "eliminated" by the "great triumvirate" of Cantor, Dedekind, and Weierstrass is refuted by an uninterrupted chain of work on infinitesimal-enriched number systems. The elimination claim is an oversimplification created by triumvirate followers, who tend to view the history of analysis as a pre-ordained march toward the radiant future of Weierstrassian epsilontics. In the present text, we document distortions of the history of analysis stemming from the triumvirate ideology of ontological minimalism, which identified the continuum with a single number system. Such anachronistic distortions characterize the received interpretation of Stevin, Leibniz, d'Alembert, Cauchy, and others.Comment: 46 pages, 4 figures; Foundations of Science (2012). arXiv admin note: text overlap with arXiv:1108.2885 and arXiv:1110.545

Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10

AIMS/HYPOTHESIS: There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. METHODS: We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. RESULTS: Detemir and glargine each displayed a balanced affinity for insulin receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤ 1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. CONCLUSIONS: Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir

Prediagnostic Serum Organochlorine Concentrations and Metastatic Prostate Cancer: A Nested Case–Control Study in the Norwegian Janus Serum Bank Cohort

BackgroundOrganochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern.ObjectivesWe conducted a nested case–control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway.MethodsSera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression.ResultsMetastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log–transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02).ConclusionsOur study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer.CitationKoutros S, Langseth H, Grimsrud TK, Barr DB, Vermeulen R, Portengen L, Wacholder S, Beane Freeman LE, Blair A, Hayes RB, Rothman N, Engel LS. 2015. Prediagnostic serum organochlorine concentrations and metastatic prostate cancer: a nested case–control study in the Norwegian Janus Serum Bank cohort. Environ Health Perspect 123:867–872; http://dx.doi.org/10.1289/ehp.140824

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure–response relationships

Objectives: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. Methods: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. Results: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. Conclusion: The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM

Remarkable convergent evolution in specialized parasitic Thecostraca (Crustacea)

<p>Abstract</p> <p>Background</p> <p>The Thecostraca are arguably the most morphologically and biologically variable group within the Crustacea, including both suspension feeders (Cirripedia: Thoracica and Acrothoracica) and parasitic forms (Cirripedia: Rhizocephala, Ascothoracida and Facetotecta). Similarities between the metamorphosis found in the Facetotecta and Rhizocephala suggests a common evolutionary origin, but until now no comprehensive study has looked at the basic evolution of these thecostracan groups.</p> <p>Results</p> <p>To this end, we collected DNA sequences from three nuclear genes [18S rRNA (2,305), 28S rRNA (2,402), Histone H3 (328)] and 41 larval characters in seven facetotectans, five ascothoracidans, three acrothoracicans, 25 rhizocephalans and 39 thoracicans (ingroup) and 12 Malacostraca and 10 Copepoda (outgroup). Maximum parsimony, maximum likelihood and Bayesian analyses showed the Facetotecta, Ascothoracida and Cirripedia each as monophyletic. The better resolved and highly supported DNA maximum likelihood and morphological-DNA Bayesian analysis trees depicted the main phylogenetic relationships within the Thecostraca as (Facetotecta, (Ascothoracida, (Acrothoracica, (Rhizocephala, Thoracica)))).</p> <p>Conclusion</p> <p>Our analyses indicate a convergent evolution of the very similar and highly reduced slug-shaped stages found during metamorphosis of both the Rhizocephala and the Facetotecta. This provides a remarkable case of convergent evolution and implies that the advanced endoparasitic mode of life known from the Rhizocephala and strongly indicated for the Facetotecta had no common origin. Future analyses are needed to determine whether the most recent common ancestor of the Thecostraca was free-living or some primitive form of ectoparasite.</p

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure-response relationships

OBJECTIVES: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. METHODS: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. RESULTS: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. CONCLUSION: The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene