Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Prolactin-modulated gene expression profiles in pancreatic islets from adult female rats

The effects of prolactin (PRL) on transcript profile expression in 24 h cultured pancreatic adult rat islets were investigated by cDNA expression array analysis to identify possible candidate mRNA species that encode proteins involved in the maturation and growth of the endocrine pancreas. The expression of 54 out of 588 genes was altered by treatment with PRL. The differentially expressed transcripts identified were distributed in six main categories involved in cell proliferation and differentiation, namely, cell cycle regulation, signal transduction, transcription factors and coactivators, translational machinery, Ca2+-mediated exocytosis, and immuno-response. Treatment with PRL also reduced the expression of genes related to apoptosis. Several genes, whose expression was previously not known to be modulated by PRL were also identified including macrophage migration inhibitory factor and Ca2+/calmodulin-dependent protein kinase IV. These genes have recently been shown to play a crucial role in insulin secretion and insulin gene expression, respectively. Treatment with PRL also modified the expression of AKT2 and bone morphogenetic protein receptor 1A that control glucose homeostasis and directly affect the behavior of endocrine pancreas and/or the sensitivity of target tissues to insulin. In conclusion, PRL induces several patterns of gene expression in pancreatic islet cells. The analysis of these different patterns will be useful for understanding the complex mechanism of action of PRL in the maturation and differentiation of pancreatic islets. (C) 2004 Elsevier Ireland Ltd. All rights reserved.22041671415

Signal transducer and activator of transcription 3-regulated sarcoendoplasmic reticulurn Ca2+-ATPase 2 expression by prolactin and glucocorticoids is involved in the adaptation of insulin secretory response during the peripartum period

During pregnancy, the maternal endocrine pancreas undergoes, as a consequence of placental lactogens and prolactin (PR,L) action, functional changes that are characterized by increased glucose-induced insulin secretion. After delivery, the maternal endocrine pancreas rapidly returns to nonpregnant state, which is mainly attributed to the increased serum levels of glucocorticoids (GCs). Although GCs are known to decrease insulin secretion and counteract PRL action, the mechanisms for these effects are poorly understood. We have previously demonstrated that signal transducer and activator of transcription 3 (STAT3) is increased in islets treated with PRL. In the present study, we show that STAT3 expression and serine phosphorylation are increased in pancreatic islets at the end of pregnancy (P19). STAT3 serine phosphorylation rapidly returned to basal levels 3 days after delivery (U). The expression of the sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2), a crucial protein involved in the regulation of calcium handling in P-cells, was also increased in P19, returning to basal levels at L3. PRL increased SERCA2 and STAT3 expressions and STAT3 serine phosphorylation in RINm5F cells. The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. Moreover, PRL-induced STAT3 serine phosphorylation and SERCA2 expression were inhibited by dexamethasone (DEX). Insulin secretion from islets of PI 9 rats pre-incubated with thapsigargin and L3 rats showed a dramatic suppression of first phase of insulin release. The present results indicate that PRL regulates SERCA2 expression by a STAT3-dependent mechanism. PRL effect is counteracted by DEX and might contribute to the adaptation of maternal endocrine pancreas during the peripartum period.1951172

The embryo as moral work object: PGD/IVF staff views and experiences

Copyright @ 2008 the authors. This article is available in accordance with the Creative Commons Deed, Attribution 2.5, see http://creativecommons.org/licenses/by-nc-nd/2.5/deed.en_CA.We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of ‘affected’ or ‘spare’ embryos or using them for research. A variety of views were expressed on the ‘embryo question’ in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as ‘moral work objects’. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of ‘work objects’ and focusing on negotiation of the social order in a morally contested field.The Wellcome Trust Biomedical Ethics Programme, who funded the projects‘Facilitating choice, framing choice: the experience of staff working in pre-implantation genetic diagnosis’ (no: 074935), and ‘Ethical Frameworks for Embryo Donation:the views and practices of IVF/PGD staff’ (no: 081414)

KC 4.1: Rural heritage and urban-rural linkages in the ICOMOS SDGs Policy Guidance

This Knowledge Café aims to provide a discussion platform to contribute to the drafting of a new ICOMOS SDGs Policy Guidance, from the perspective of rural heritage, landscapes and rural-urban linkages. While 50%-plus of global populations are urban dwellers, we tend to forget that the other half dwell in rural places. One of the 7 Priority Actions of the ICOMOS SDGs Working Group in 2018 is the preparation of a consolidated policy statement, as an effective tool for advocacy and communication to wider society and the development world. Based on the need to boost the role of cultural heritage in sustainable development processes, this would be a robust Policy Guidance document, serving to improve the recognition of the role of cultural heritage protection, particularly as defined by SDG 11.4 and the New Urban Agenda. The ICOMOS SDGs Working Group aims to launch this document at the 10th World Urban Forum in 2020 and at the High-Level Political Forum in 2021. The new Policy Guidance aims to emphasize “heritage as a resource, a strategic opportunity”, using the framework of the 3 dimensions of sustainability, economic, social, environmental, and propose adding the 4th dimension of ‘culture’ through an appropriate approach. The document should be based on solid scientific expertise sourced from ICOMOS membership. The Symposium on Rural Heritage: Landscapes and Beyond is a prime opportunity to involve some of this membership, ensuring a diverse and inclusive range of expertise in heritage informs the Policy Guidance. Rural heritage and landscapes, including rural-urban linkages, have great relevance for the intersection of cultural heritage and sustainable development, touching on many SDGs and issues raised in the New Urban Agenda, not to mention the Historic Urban Landscape Recommendation. To cite some examples of this inter-connectedness, the “inter-related categories of continuity and change” addressed during the Symposium, provide the following links: - under ‘Rural Culture’ to SDG 11.4 (change management for tangible rural heritage), SDG 1.5, 2.4, 11.5, 11.b, 13.1 (risk of loss of intangible rural traditions/ practices), SDG 8.9, SDG 12.b (rural cultural tourism), SDG 16.7, 16.a, 17.9, 17.15, 17.17 (identity of people and places); - under ‘Rural economics’ to SDG 1 (poverty eradication), SDG2 (food security), SDG3 (rural agricultural heritage), SDG 8 (improvement of markets and opportunities for rural traditional tools, techniques and rural heritage tourism), SDG 8 (infrastructure, services to small enterprises), SDG 11 (spatial form, territorial policies); - under ‘Rural Environment’ to SDG 6 (water), 13 and 15 (desertification, climate-induced severe weather events, biodiversity, forest management); and - under ‘Rural Society’ to SDG 1 (poverty alleviation) SDG 2 (agriculture), SDG 3.8, 3.c (health services), SDG 16, 17 (bottom-up governance). - Some case studies from ‘Moroccan Rural Heritage’ can be proposed during the session from participants who may have relevant knowledge, to demonstrate these links. The Knowledge Café will feature two speakers, Ege Yildirim and Patricia O’Donnell, giving the conceptual framework of the session, followed by Ilaria Rosetti presenting the method of open discussion, whereby breakout groups (e.g. 3-4 groups of 5-6) can discuss the links of rural heritage issues to the various 17 Goals and Targets under them, concluding with short reporting from each group, to be compiled and disseminated later by the conveners

Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation

Tribbles pseudokinase-3 (TRIB3) has been proposed to act as an inhibitor of AKT although the precise molecular basis of this activity and whether the loss of TRIB3 contributes to cancer initiation and progression remain to be clarified. In this study, by using a wide array of in vitro and in vivo approaches, including a Trib3 knockout mouse, we demonstrate that TRIB3 has a tumor-suppressing role. We also find that the mechanism by which TRIB3 loss enhances tumorigenesis relies on the dysregulation of the phosphorylation of AKT by the mTORC2 complex, which leads to an enhanced phosphorylation of AKT on Ser473 and the subsequent hyperphosphorylation and inactivation of the transcription factor FOXO3. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis