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- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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- Neri, L, et al.
(författare)
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Improved design of proton source and low energy beam transport line for European Spallation Source.
- 2014
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 85:2
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Tidskriftsartikel (refereegranskat)abstract
- The design update of the European Spallation Source (ESS) accelerator is almost complete and the construction of the prototype of the microwave discharge ion source able to provide a proton beam current larger than 70 mA to the 3.6 MeV Radio Frequency Quadrupole (RFQ) started. The source named PS-ESS (Proton Source for ESS) was designed with a flexible magnetic system and an extraction system able to merge conservative solutions with significant advances. The ESS injector has taken advantage of recent theoretical updates and new plasma diagnostics tools developed at INFN-LNS (Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare). The design strategy considers the PS-ESS and the low energy beam transport line as a whole, where the proton beam behaves like an almost neutralized non-thermalized plasma. Innovative solutions have been used as hereinafter described. Thermo-mechanical optimization has been performed to withstand the chopped beam and the misaligned focused beam over the RFQ input collimator; the results are reported here.
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- Matikainen, N., et al.
(författare)
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Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men
- 2017
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Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 27:6, s. 534-542
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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- Ashjaei, Seyed Mohammad Hossein, 1980-, et al.
(författare)
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Time-Sensitive Networking in automotive embedded systems : State of the art and research opportunities
- 2021
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Ingår i: Journal of systems architecture. - : Elsevier B.V.. - 1383-7621 .- 1873-6165. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- The functionality advancements and novel customer features that are currently found in modern automotive systems require high-bandwidth and low-latency in-vehicle communications, which become even more compelling for autonomous vehicles. In a recent effort to meet these requirements, the IEEE Time-Sensitive Networking (TSN) task group has developed a set of standards that introduce novel features in Switched Ethernet. TSN standards offer, for example, a common notion of time through accurate and reliable clock synchronization, delay bounds for real-time traffic, time-driven transmissions, improved reliability, and much more. In order to fully utilize the potential of these novel protocols in the automotive domain, TSN should be seamlessly integrated into the state-of-the-art and state-of-practice model-based development processes for automotive embedded systems. Some of the core phases in these processes include software architecture modeling, timing predictability verification, simulation, and hardware realization and deployment. Moreover, throughout the development of automotive embedded systems, the safety and security requirements specified on these systems need to be duly taken into account. In this context, this work provides an overview of TSN in automotive applications and discusses the recent technological developments relevant to the adoption of TSN in automotive embedded systems. The work also points at the open challenges and future research directions.
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- De Caterina, Raffaele, et al.
(författare)
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Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation : an analysis of the ARISTOTLE trial.
- 2020
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 8:3, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial.METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001.CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.
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| 11. |
- Harrison, Gregory A., et al.
(författare)
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Inducing vulnerability to InhA inhibition restores isoniazid susceptibility in drug-resistant Mycobacterium tuberculosis
- 2024
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Of the approximately 10 million cases of Mycobacterium tuberculosis (Mtb) infections each year, over 10% are resistant to the frontline antibiotic isoniazid (INH). INH resistance is predominantly caused by mutations that decrease the activity of the bacterial enzyme KatG, which mediates the conversion of the pro-drug INH to its active form INH-NAD. We previously discovered an inhibitor of Mtb respiration, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a collection of INH-resistant mutants to INH through an unknown mechanism. To investigate the mechanism of action of C10, we exploited the toxicity of high concentrations of C10 to select for resistant mutants. We discovered two mutations that confer resistance to the disruption of energy metabolism and allow for the growth of Mtb in high C10 concentrations, indicating that growth inhibition by C10 is associated with inhibition of respiration. Using these mutants as well as direct inhibitors of the Mtb electron transport chain, we provide evidence that inhibition of energy metabolism by C10 is neither sufficient nor necessary to potentiate killing by INH. Instead, we find that C10 acts downstream of INH-NAD synthesis, causing Mtb to become particularly sensitive to inhibition of the INH-NAD target, InhA, without changing the concentration of INH-NAD or the activity of InhA, the two predominant mechanisms of potentiating INH. Our studies revealed that there exists a vulnerability in Mtb that can be exploited to render Mtb sensitive to otherwise subinhibitory concentrations of InhA inhibitor. IMPORTANCE Isoniazid (INH) is a critical frontline antibiotic to treat Mycobacterium tuberculosis (Mtb) infections. INH efficacy is limited by its suboptimal penetration of the Mtb-containing lesion and by the prevalence of clinical INH resistance. We previously discovered a compound, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a set of INH-resistant mutants to INH. Resistance is typically mediated by katG mutations that decrease the activation of INH, which is required for INH to inhibit the essential enzyme InhA. Our current work demonstrates that C10 re-sensitizes INH-resistant katG-hypomorphs without enhancing the activation of INH. We furthermore show that C10 causes Mtb to become particularly vulnerable to InhA inhibition without compromising InhA activity on its own. Therefore, C10 represents a novel strategy to curtail the development of INH resistance and to sensitize Mtb to sub-lethal doses of INH, such as those achieved at the infection site.
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- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 15. |
- Lo Bello, L., et al.
(författare)
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Schedulability analysis of Time-Sensitive Networks with scheduled traffic and preemption support
- 2020
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Ingår i: Journal of Parallel and Distributed Computing. - : Academic Press Inc.. - 0743-7315 .- 1096-0848. ; 144, s. 153-171
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Tidskriftsartikel (refereegranskat)abstract
- The Time-Sensitive Networking (TSN) set of standards introduces in IEEE 802.1 switches and end stations novel features to meet the requirements of a broad spectrum of applications that are characterized by time-sensitive and mission-critical traffic flows. In particular, the IEEE802.1Qbv-2015 amendment introduces enhancements that provide temporal isolation for scheduled traffic, i.e., a traffic class that requires transmission based on a known timescale, while the IEEE802.1Qbu-2016 introduces preemption as a mechanism to allow time-critical messages to interrupt ongoing non time-critical transmissions. Both amendments, that are now enrolled in the IEEE802.1Q-2018 standard, are very important for industrial networks, where scheduled traffic and low-latency real-time flows have to coexist, on the same network, with best-effort transmissions. In this context, this work presents a response time analysis of TSN networks that encompasses the enhancements for scheduled traffic and preemption, in various combinations. The paper presents the proposed analysis and a performance comparison between the response times calculated by the analysis and the response times obtained through OMNeT++ simulations in three different scenarios. © 2020 Elsevier Inc.
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- Tideman, Eva, et al.
(författare)
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Hur ska ABAS-II användas?
- 2008
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Ingår i: ABAS-II: Adaptive Behavior Assessment System: Manual, 2. ed. Svensk version. ; , s. 67-92
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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