| 1. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 3. |
- Dong, C. L., et al.
(författare)
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Electronic structure and surface structure of Cu2S nanorods from polarization dependent X-ray absorption spectroscopy
- 2006
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 151:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Highly aligned CuS nanorods have been studied by polarization dependent X-ray absorption spectroscopy. In contrast to bulk Cu2S, strong s, p, and d hybridization is found in the nanorods. The polarization dependence shows a predominant d(z2) character of Cu 3d states. Ab initio multiple-scattering calculations confirm the strong hybridization, and reveal that CuS nanorods are grown along the z-axis of chalcocite structure with Cu-7 and Cu-10 sites being the main building blocks. The hybridized absorption peak in the nanorods is shifted towards lower energies for smaller diameter of nanorods, which is attributed to surface reconstruction due to strong Cu-Cu interactions on the Cu-rich surface of the nanorods.
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| 4. |
- Chen, Yuqing, et al.
(författare)
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Naturally occurring human genetic variation in the 3'-untranslated region of the secretory protein chromogranin A is associated with autonomic blood pressure regulation and hypertension in a sex-dependent fashion
- 2008
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 52:18, s. 1468-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We aimed to determine whether the common variation at the chromogranin A (CHGA) locus increases susceptibility to hypertension. BACKGROUND: CHGA regulates catecholamine storage and release. Previously we systematically identified genetic variants across CHGA. METHODS: We carried out dense genotyping across the CHGA locus in >1,000 individuals with the most extreme blood pressures (BPs) in the population, as well as twin pairs with autonomic phenotypes. We also characterized the function of a trait-associated 3'-untranslated region (3'-UTR) variant with transfected CHGA 3'-UTR/luciferase reporter plasmids. RESULTS: CHGA was overexpressed in patients with hypertension, especially hypertensive men, and CHGA predicted catecholamines. In individuals with extreme BPs, CHGA genetic variants predicted BP, especially in men, with a peak association occurring in the 3'-UTR at C+87T, accounting for up to approximately 12/ approximately 9 mm Hg. The C+87T genotype predicted CHGA secretion in vivo, with the +87T allele (associated with lower BP) also diminishing plasma CHGA by approximately 10%. The C+87T 3'-UTR variant also predicted the BP response to environmental (cold) stress; the same allele (+87T) that diminished basal BP in the population also decreased the systolic BP response to stress by approximately 12 mm Hg, and the response was smaller in women (by approximately 6 mm Hg). In a chromaffin cell-transfected CHGA 3'-UTR/luciferase reporter plasmid, the +87T allele associated with lower BP also decreased reporter expression by approximately 30%. In cultured chromaffin cells, reducing endogenous CHGA expression by small interfering ribonucleic acid caused approximately two-thirds depletion of catecholamine storage vesicles. CONCLUSIONS: Common variant C+87T in the CHGA 3'-UTR is a functional polymorphism causally associated with hypertension especially in men of the population, and we propose steps ("intermediate phenotypes") whereby in a sex-dependent fashion this genetic variant influences the ultimate disease trait. These observations suggest new molecular strategies to probe the pathophysiology, risk, and rational treatment of hypertension.
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| 5. |
- Gao, Feng, et al.
(författare)
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Effects of substrate temperature on Bi0.8La0.2FeO3 thin films prepared by pulsed laser deposition
- 2007
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Ingår i: Thin Solid Films. - : Elsevier. - 0040-6090 .- 1879-2731. ; 515:13, s. 5366-5373
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Tidskriftsartikel (refereegranskat)abstract
- Bi0.8La0.2FeO3 thin films on Pt/TiO2/SiO2/Si substrates at various substrate temperatures from 500 degrees C to 750 degrees C are prepared by pulsed laser deposition, and their microstructures and ferroelectric/magnetic properties are carefully investigated using various techniques. It is observed that the crystallographic orientation and Fe-ion valence state depend significantly on the substrate temperature, which consequently influences considerably on the ferroelectric and magnetic properties of the thin films. A considerable improvement of the ferroelectric and magnetic properties of the thin films can be achieved by optimizing the substrate temperature for deposition. (C) 2007 Elsevier B.V. All rights reserved.
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| 6. |
- Garrison, Sean P, et al.
(författare)
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Selection against PUMA gene expression in Myc-driven B-cell lymphomagenesis.
- 2008
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Ingår i: Molecular and cellular biology. - 1098-5549. ; 28:17, s. 5391-402
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Tidskriftsartikel (refereegranskat)abstract
- The p53 tumor suppressor pathway limits oncogenesis by inducing cell cycle arrest or apoptosis. A key p53 target gene is PUMA, which encodes a BH3-only proapoptotic protein. Here we demonstrate that Puma deletion in the Emu-Myc mouse model of Burkitt lymphoma accelerates lymphomagenesis and that approximately 75% of Emu-Myc lymphomas naturally select against Puma protein expression. Furthermore, approximately 40% of primary human Burkitt lymphomas fail to express detectable levels of PUMA and in some tumors this is associated with DNA methylation. Burkitt lymphoma cell lines phenocopy the primary tumors with respect to DNA methylation and diminished PUMA expression, which can be reactivated following inhibition of DNA methyltransferases. These findings establish that PUMA is silenced in human malignancies, and they suggest PUMA as a target for the development of novel chemotherapeutics.
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| 7. |
- Gebe, John A, et al.
(författare)
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Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.
- 2006
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 121:3, s. 294-304
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Tidskriftsartikel (refereegranskat)abstract
- We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice
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| 8. |
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| 9. |
- Kaneda, Atsushi, et al.
(författare)
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Enhanced sensitivity to IGF-II signalling links loss of imprinting of IGF2 to increased cell proliferation and tumour risk
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:52, s. 20926-20931
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Tidskriftsartikel (refereegranskat)abstract
- Loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to abnormal activation of the normally silent maternal allele, is a common human epigenetic population variant associated with a 5-fold increased frequency of colorectal neoplasia. Here, we show first that LOI leads specifically to increased expression of proliferation-related genes in mouse intestinal crypts. Surprisingly, LOI(+) mice also have enhanced sensitivity to IGF-II signaling, not simply increased IGF-II levels, because in vivo blockade with NVP-AEW541, a specific inhibitor of the IGF-II signaling receptor, showed reduction of proliferation-related gene expression to levels half that seen in LOI(-) mice. Signal transduction assays in microfluidic chips confirmed this enhanced sensitivity with marked augmentation of Akt/PKB signaling in LOI(+) cells at low doses of IGF-II, which was reduced in the presence of the inhibitor to levels below those found in LOI(-) cells, and was associated with increased expression of the IGF1 and insulin receptor genes. We exploited this increased IGF-II sensitivity to develop an in vivo chemopreventive strategy using the azoxymethane (AOM) mutagenesis model. LOI(+) mice treated with AOM showed a 60% increase in premalignant aberrant crypt foci (ACF) formation over LOI(-) mice. In vivo IGF-II blockade with NVP-AEW541 abrogated this effect, reducing ACF to a level 30% lower even than found in exposed LOI(-) mice. Thus, LOI increases cancer risk in a counterintuitive way, by increasing the sensitivity of the IGF-II signaling pathway itself, providing a previously undescribed epigenetic chemoprevention strategy in which cells with LOI are "IGF-II addicted" and undergo reduced tumorigenesis in the colon upon IGF-II pathway blockade.
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| 10. |
- Li, Wen, et al.
(författare)
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Recognition of aminoacyl-tRNA : a common molecular mechanism revealed by cryo-EM
- 2008
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 27:24, s. 3322-3331
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Tidskriftsartikel (refereegranskat)abstract
- The accuracy of ribosomal translation is achieved by an initial selection and a proofreading step, mediated by EF-Tu, which forms a ternary complex with aminoacyl(aa)-tRNA. To study the binding modes of different aa-tRNAs, we compared cryo-EM maps of the kirromycin-stalled ribosome bound with ternary complexes containing Phe-tRNA(Phe), Trp-tRNA(Trp), or Leu-tRNA(LeuI). The three maps suggest a common binding manner of cognate aa-tRNAs in their specific binding with both the ribosome and EF-Tu. All three aa-tRNAs have the same 'loaded spring' conformation with a kink and twist between the D-stem and anticodon stem. The three complexes are similarly integrated in an interaction network, extending from the anticodon loop through h44 and protein S12 to the EF-Tu-binding CCA end of aa-tRNA, proposed to signal cognate codon-anticodon interaction to the GTPase centre and tune the accuracy of aa-tRNA selection.
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