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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are 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 monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Battistoni, G, et al.
(författare)
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FLUKA Monte Carlo calculations for hadrontherapy application
- 2013
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Ingår i: CERN-Proceedings-2012-002. ; , s. 461-467
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Konferensbidrag (refereegranskat)abstract
- Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models for the description of the transport and the interaction of all components of the expected radiation field (ions, hadrons, electrons, positrons and photons). This contribution will address the specific case of the general-purpose particle and interaction code FLUKA. In this work, an application of FLUKA will be presented, i.e. establishing CT (computed tomography)-based calculations of physical and RBE (relative biological effectiveness)-weighted dose distributions in scanned carbon ion beam therapy.
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| 9. |
- Ballarini, F., et al.
(författare)
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The physics of the FLUKA code : Recent developments
- 2007
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Ingår i: Advances in Space Research. - Elsevier : Elsevier BV. - 0273-1177 .- 1879-1948. ; 40:9, s. 1339-1349
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Tidskriftsartikel (refereegranskat)abstract
- FLUKA is a Monte-Carlo code able to simulate interaction and transport of hadrons, heavy ions and electromagnetic particles from few keV (or thermal neutron) to cosmic ray energies in whichever material. The highest priority in the design and development of the code has always been the implementation and improvement of sound and modern physical models. A summary of the FLUKA physical models is given, while recent developments are described in detail: among the others, extensions of the intermediate energy hadronic interaction generator, refinements in photon cross sections and interaction models, analytical on-line evolution of radio-activation and remnant dose. In particular, new developments in the nucleus-nucleus interaction models are discussed. Comparisons with experimental data and examples of applications of relevance for space radiation are also provided.
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| 10. |
- Battistoni, G., et al.
(författare)
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The FLUKA code and its use in hadron therapy
- 2008
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Ingår i: Nuovo Cimento della Societa Italiana di Fisica C. - Italian Physical Society. - 1124-1896. ; 31:1, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- FLUKA is a multipurpose Monte Carto code describing transport and interaction with matter of a, large variety of particles over a wide energy range ill complex geometries. FLUKA is successfully applied ill several fields, including, but not only particle physics, cosmic-ray physics, dosimetry, radioprotection, hadron therapy. space radiation, accelerator design and neutronics. Here we briefly review recent model developments and provide examples of applications to hadron therapy, including calculation of physical and biological dose for comparison with analytical treatment planning engines as well as beta(+)-activation for therapy monitoring by means of positron emission tomography.
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| 11. |
- Pinsky, L., et al.
(författare)
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Measurement of Fragmentation Products including Angular Distributions for 3, 5, and 10 GeV/A C and Si on several nuclear targets at the AGS
- 2010
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Ingår i: 2009 12th International Conference on Nuclear Reaction Mechanisms, NRM 2009; Varenna; Italy; 15 June 2009 through 19 June 2009. - 2078-8835. - 9789290833413 ; 2, s. 431-437
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Konferensbidrag (refereegranskat)abstract
- Motivated by differences in the predicted fragmentation of heavy ions at energies around 5 GeV/A as employed in the event generators used by the FLUKA Monte Carlo Code [1], a set of measurements were carried out at the AGS facility at the Brookhaven National Laboratory to determine as much information as possible about the cross sections to allow harmonization of those event generators for these incident lab energies. The FLUKA Code employs the RQMD event generator of Sorge [2] for heavy ion interactions starting at 100 MeV/A and extending into the region around 5 GeV/A. Above those energies the DPMJET code of Ranft and Roesler [3] is typically employed to simulate such interactions. The detailed predictions of these event generators had some disagreement in the vicinity of this crossover energy and in order to tune these codes to be in closer harmony at the transition, and of course to be simulating nature as closely as possible, data were taken at 3, 5 and 10 GeV/A with beams of Fe, Si and C on a variety of targets including C, A1. Fe and Cu. The Fe data have not been fully analyzed, but results from the C and Si beams are available and the forward fragment spectrum along with a measurement of the charged particle angular distribution in a set of Si strip detectors out to about 45 degrees in the lab are available. These include sufficient statistics to provide the charged particle distributions as a function of the major projectile fragment. The detectors used in this measurement were based on what were reasonably available to us, and as such were limited in capability, and required separate data acquisition systems. Nevertheless, spectra were obtained that should be sufficient to enable the harmonization of the event generator codes at the crossover energy. This paper discusses only the experimental results and not the impact of those results on the FLUKA code.
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| 12. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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- Campanella, A., et al.
(författare)
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Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments : A study by ERIC, the European Research Initiative on CLL
- 2024
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Ingår i: American Journal of Hematology. - : John Wiley & Sons. - 0361-8609 .- 1096-8652. ; 99:4, s. 745-750
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.
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| 17. |
- Campanella, Gianluca, et al.
(författare)
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Epigenome-wide association study of adiposity and future risk of obesity-related diseases
- 2018
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 42:12, s. 2022-2035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waistheight ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P=9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P=6.00×10−7), higher triglyceride levels (P=5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P=1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P<1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P<1.25×10−3), independently of obesity and established risk factors.Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.
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| 18. |
- Chadeau-Hyam, M., et al.
(författare)
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Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:5, s. 1065-1072
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.METHODS:We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.RESULTS:Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.CONCLUSIONS:This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
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| 19. |
- Kundrat, J., et al.
(författare)
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GNPy YANG : Open APIs for End-to-End Service Provisioning in Optical Networks
- 2021
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Ingår i: 2021 Optical Fiber Communications Conference and Exhibition, OFC 2021 - Proceedings. - : Institute of Electrical and Electronics Engineers Inc.. - 9781943580866
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Konferensbidrag (refereegranskat)abstract
- We demonstrate end-to-end service provisioning in a fully disaggregated optical network using open software interfaces. The GNPy quality-of-transmission estimator is extended with a YANG-based API. The YANG modeling work builds on the IETF standard schemas, and describes multiple layers of the network at once.
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| 20. |
- Cozzolino, Carlo A., et al.
(författare)
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Microfibrillated cellulose and borax as mechanical, O-2-barrier, and surface-modulating agents of pullulan biocomposite coatings on BOPP
- 2016
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 143, s. 179-187
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Tidskriftsartikel (refereegranskat)abstract
- Multifunctional composite coatings on bi-oriented polypropylene (BOPP) films were obtained using borax and microfibrillated cellulose (MFC) added to the main pullulan coating polymer. Spectroscopy analyses suggested that a first type of interaction occurred via hydrogen bonding between the C-6-OH group of pullulan and the hydroxyl groups of boric acid, while monodiol and didiol complexation represented a second mechanism. The deposition of the coatings yielded an increase in the elastic modulus of the entire plastic substrate (from similar to 2 GPa of the neat BOPP to similar to 3.1 GPa of the P/B+/MFC-coated BOPP). The addition of MFC yielded a decrease of both static and kinetic coefficients of friction of approximately 22% and 25%, respectively, as compared to the neat BOPP. All composite coatings dramatically increased the oxygen barrier performance of BOPP, especially under dry conditions. The deposition of the high hydrophilic coatings allowed to obtain highly wettable surfaces (water contact angle of similar to 18 degrees).
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