Local Quantum Measurement and No-Signaling Imply Quantum Correlations

We show that, assuming that quantum mechanics holds locally, the finite speed of information is the principle that limits all possible correlations between distant parties to be quantum mechanical as well. Local quantum mechanics means that a Hilbert space is assigned to each party, and then all local positive-operator-valued measurements are (in principle) available; however, the joint system is not necessarily described by a Hilbert space. In particular, we do not assume the tensor product formalism between the joint systems. Our result shows that if any experiment would give nonlocal correlations beyond quantum mechanics, quantum theory would be invalidated even locally.Comment: Published version. 5 pages, 1 figure

Kankerrisico’s : kunnen we nog iets leren van de muis?

Niet UB, maar tijdelijk ter bevordering van de PDF bestanden in het Leids Repositorium

Toepassingsmogelijkheden van Modified Atmosphere Packaging (MAP) in rozen en sierheesters

Boomkwekerijgewassen, zoals rozen en siergewassen, zijn in diverse stadia van de keten gevoelig voor kwaliteitsverlies. Dit kan uitdroging zijn door vochttekort, verrotting bij vochtovermaat of ongewenst uitlopen van het product. Uit eerder onderzoek is gebleken dat toepassing van zogenaamde Modified Atmosphere folies (MA, zie kader) al dan niet in combinatie met bepaalde vulmiddelen dergelijke problemen sterk kan verminderen en daarmee de houdbaarheid van producten kan verlengen. Dit rapport geeft de resultaten van een onderzoek naar de mogelijkheden van toepassing van MA-folie bij bewaring van rozen en siergewassen in verschillende delen van de keten

TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts

Abstract3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:C>T:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision repair (NER) on 3-NBA-induced mutagenesis of the human tumour suppressor gene TP53 and the reporter gene lacZ. To this end we utilised Xpa -knockout (Xpa-Null) human TP53 knock-in (Hupki) embryo fibroblasts (HUFs). As Xpa is essential for NER of bulky DNA adducts, we hypothesized that DNA adducts induced by 3-NBA would persist in the genomes of Xpa-Null cells and lead to an increased frequency of mutation. The HUF immortalisation assay was used to select for cells harbouring TP53 mutations following mutagen exposure. We found that Xpa-Null Hupki mice and HUFs were more sensitive to 3-NBA treatment than their wild-type (Xpa-WT) counterparts. However, following 3-NBA treatment and immortalisation, a similar frequency of TP53-mutant clones arose from Xpa-WT and Xpa-Null HUF cultures. In cells from both Xpa genotypes G:C>T:A transversion was the predominant TP53 mutation type and mutations exhibited bias towards the non-transcribed strand. Thirty-two percent of 3-NBA-induced TP53 mutations occurred at CpG sites, all of which are hotspots for mutation in smokers’ lung cancer (codons 157, 158, 175, 245, 248, 273, 282). We also examined 3-NBA-induced mutagenesis of an integrated lacZ reporter gene in HUFs, where we again observed a similar mutant frequency in Xpa-WT and Xpa-Null cells. Our findings suggest that 3-NBA-DNA adducts may evade removal by global genomic NER; the persistence of 3-NBA adducts in DNA may be an important factor in its mutagenicity

Does clinical management improve outcomes following self-Harm? Results from the multicentre study of self-harm in England

Background Evidence to guide clinical management of self-harm is sparse, trials have recruited selected samples, and psychological treatments that are suggested in guidelines may not be available in routine practice. Aims To examine how the management that patients receive in hospital relates to subsequent outcome. Methods We identified episodes of self-harm presenting to three UK centres (Derby, Manchester, Oxford) over a 10 year period (2000 to 2009). We used established data collection systems to investigate the relationship between four aspects of management (psychosocial assessment, medical admission, psychiatric admission, referral for specialist mental health follow up) and repetition of self-harm within 12 months, adjusted for differences in baseline demographic and clinical characteristics. Results 35,938 individuals presented with self-harm during the study period. In two of the three centres, receiving a psychosocial assessment was associated with a 40% lower risk of repetition, Hazard Ratios (95% CIs): Centre A 0.99 (0.90–1.09); Centre B 0.59 (0.48–0.74); Centre C 0.59 (0.52–0.68). There was little indication that the apparent protective effects were mediated through referral and follow up arrangements. The association between psychosocial assessment and a reduced risk of repetition appeared to be least evident in those from the most deprived areas. Conclusion These findings add to the growing body of evidence that thorough assessment is central to the management of self-harm, but further work is needed to elucidate the possible mechanisms and explore the effects in different clinical subgroups

The transcriptomic response to irinotecan in colon carcinoma bearing mice preconditioned by fasting

Background: Irinotecan use is limited due to severe toxicity. Preconditioning by fasting (PBF) protects against side effects of irinotecan while preserving its antitumor activity. The mechanisms underlying the effects of PBF still need to be elucidated. Here, we investigated the transcriptional responses of PBF on irinotecan in both tumor and healthy liver tissue. Experimental approach: Male BALB/c mice were subcutaneously injected with C26 colon carcinoma cells. Twelve days after tumor inoculation, two groups were fasted for three days and two groups were allowed food ad libitum (AL). Subsequently, both groups received one dose of irinotecan. Twelve hours after administration mice were sacrificed and blood, tumor and liver tissue were harvested. Blood samples were analyzed to determine liver, kidney and bone marrow function, tissues were used for transcriptome analyses. Key results: The AL irinotecan group showed worsened organ function and decreased leukocyte numbers. These effects were abated in PBF animals. PBF led to an altered transcriptional response in the liver of irinotecan-treated mice, including decreased cellular injury and increased stress resistance. Hepatic metabolism of irinotecan was also significantly changed due to PBF. The transcriptional response of tumor tissue observed after PBF was hardly affected compared to AL fed animals. Conclusions: Transcriptional changes after PBF to irinotecan treatment showed an improved protective stress response in healthy liver but not in tumor tissue, including changes in irinotecan metabolism. These data help to unravel the mechanisms underlying the effects of fasting on irinotecan and help to improve outcome of chemotherapeutic treatment in cancer patients

Mammary gland tumor promotion by chronic administration of IGF1 and the insulin analogue AspB10 in the p53R270H/⁺WAPCre mouse model

Insulin analogues are structurally modified molecules with altered pharmaco-kinetic and -dynamic properties compared to regular human insulin used by diabetic patients. While these compounds are tested for undesired mitogenic effects, an epidemiological discussion is ongoing regarding an association between insulin analogue therapy and increased cancer incidence, including breast cancer. Standard in vivo rodent carcinogenesis assays do not pick up this possible increased carcinogenic potential. Here we studied the role of insulin analogues in breast cancer development. For this we used the human relevant mammary gland specific p53R270H/⁺WAPCre mouse model. Animals received life long repeated treatment with four different insulin (-like) molecules: normal insulin, insulin glargine, insulin X10 (AspB10) or insulin-like growth factor 1 (IGF1). Insulin-like molecules with strong mitogenic signaling, insulin X10 and IGF1, significantly decreased the time for tumor development. Yet, insulin glargine and normal insulin, did not significantly decrease the latency time for (mammary gland) tumor development. The majority of tumors had an epithelial to mesenchymal transition phenotype (EMT), irrespective of treatment condition. Enhanced extracellular signaling related kinase (Erk) or serine/threonine kinase (Akt) mitogenic signaling was in particular present in tumors from the insulin X10 and IGF1 treatment groups. These data indicate that insulin-like molecules with enhanced mitogenic signaling increase the risk of breast cancer development. Moreover, the use of a tissue specific cancer model, like the p53R270H/⁺WAPCre mouse model, is relevant to assess the intrinsic pro-carcinogenic potential of mitogenic and non-mitogenic biologicals such as insulin analogues. INTRODUCTION METHODS RESULTS CONCLUSION

High Preservation of CpG Cytosine Methylation Patterns at Imprinted Gene Loci in Liver and Brain of Aged Mice

A gradual loss of the correct patterning of 5-methyl cytosine marks in gene promoter regions has been implicated in aging and age-related diseases, most notably cancer. While a number of studies have examined DNA methylation in aging, there is no consensus on the magnitude of the effects, particularly at imprinted loci. Imprinted genes are likely candidate to undergo age-related changes because of their demonstrated plasticity in utero, for example, in response to environmental cues. Here we quantitatively analyzed a total of 100 individual CpG sites in promoter regions of 11 imprinted and non-imprinted genes in liver and cerebral cortex of young and old mice using mass spectrometry. The results indicate a remarkably high preservation of methylation marks during the aging process in both organs. To test if increased genotoxic stress associated with premature aging would destabilize DNA methylation we analyzed two DNA repair defective mouse models showing a host of premature aging symptoms in liver and brain. However, also in these animals, at the end of their life span, we found a similarly high preservation of DNA methylation marks. We conclude that patterns of DNA methylation in gene promoters of imprinted genes are surprisingly stable over time in normal, postmitotic tissues and that the

Preparation and characterization of in situ polymerized cyclic butylene terephthalate/graphene nanocomposites

Graphene reinforced cyclic butylene terephthalate (CBT) matrix nanocomposites were prepared and characterized by mechanical and thermal methods. These nanocomposites containing different amounts of graphene (up to 5 wt%) were prepared by melt mixing with CBT that was polymerized in situ during a subsequent hot pressing. The nanocomposites and the neat polymerized CBT (pCBT) as reference material were subjected to differential scanning calorimetry (DSC), dynamical mechanical analysis (DMA), thermogravimetrical analysis (TGA) and heat conductivity measurements. The dispersion of the grapheme nanoplatelets was characterized by transmission electron microscopy (TEM). It was established that the partly exfoliated graphene worked as nucleating agent for crystallization, acted as very efficient reinforcing agent (the storage modulus at room temperature was increased by 39 and 89% by incorporating 1 and 5 wt.% graphene, respectively). Graphene incorporation markedly enhanced the heat conductivity but did not influence the TGA behaviour due to the not proper exfoliation except the ash content

Onderzoek naar het bemestingsadvies van vruchtbomen, coniferen, rozen en buxus

In 2006 is het stelsel van gebruiksnormen ingevoerd. Deze normen zijn gebaseerd op de bestaande bemestingsadviezen. Kwekers van vruchtbomen, coniferen, rozen en Buxus hebben aangegeven dat de stikstofgebruiksnormen te laag zijn om een rendabele kwaliteitsproductie te behalen. Dit betekent dat de adviezen aangepast moeten worden. Een belangrijke reden om een aanpassing van het advies en daarmee de gebruiksnorm te vragen is dat er in de periode tussen het verschijnen van de Bemestingsadviesbasis boomkwekerijgewassen en het vaststellen van de stikstofgebruiksnormen er veel zaken in de teelt van de desbetreffende gewassen is veranderd. Daarnaast zijn de bestaande adviezen veelal gebaseerd op ‘expert knowledge’ en slechts beperkt op veldproeven. Om tot een aanpassing van het bemestingsadvies te komen moeten bemestingsproeven worden uitgevoerd volgens het ‘Protocol voor de aanpassing bemestingsadviezen voor stikstof’. In dit rapport worden de proeven beschreven die voor de vier genoemde gewasgroepen gedurende een aantal jaren zijn uitgevoer