| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Natalino, Carlos, Dr. 1987-, et al.
(författare)
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Dimensioning Optical Clouds with Shared-Path Shared-Computing (SPSC) Protection
- 2015
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Ingår i: High Performance Switching and Routing (HPSR), 2015 IEEE 16th International Conference on. - : IEEE conference proceedings.
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Konferensbidrag (refereegranskat)abstract
- Service relocation represents a promising strategy to provide flexible and resource efficient resiliency from link failures in the optical cloud environment. However, when a failure affects a node hosting a datacenter (DC), service relocation from the affected DC is not possible. One alternative to protect against DC failures relies on using design strategies that duplicate the IT (i.e., storage and processing) resources in a backup DC at the expense of increasing resource overbuild (i.e., cost) of the network. This work proposes a dimensioning strategy based on the shared-path shared-computing (SPSC) concept able to protect against any single link, server, or DC failure scenario with minimal resource overbuild for the network and IT infrastructures. SPSC is based on the intuition that only storage units need complete replication in backup DC, while processing units can be instantiated only after the occurrence of a failure, leaving the design strategy some leeway to minimize their number. As result, the proposed SPSC design shows a considerable reduction in the amount of backup resources when compared to the dedicated protection strategies.
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| 3. |
- Natalino, Carlos, 1987-, et al.
(författare)
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Lifetime-Aware Provisioning in Green Optical Backbone Networks
- 2016
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Ingår i: 2016 OPTICAL FIBER COMMUNICATIONS CONFERENCE AND EXHIBITION (OFC). - Washington, D.C. : Optical Society of America.
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Konferensbidrag (refereegranskat)abstract
- We present a framework able to limit the device lifetime degradation in optical backbone networks using sleep-mode-based green strategies. Results show that our approach manages the lifetime while not compromising significantly the energy saving performance.
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| 4. |
- Natalino, Carlos, 1987-, et al.
(författare)
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Restoration in Optical Cloud Networks With Relocation and Services Differentiation
- 2016
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Ingår i: Journal of Optical Communications and Networking. - : Optical Society of America. - 1943-0620 .- 1943-0639. ; 8:2, s. 100-111
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Tidskriftsartikel (refereegranskat)abstract
- Optical cloud networks allow for the integrated management of both optical and IT resources. In this paradigm, cloud services can be provisioned in an anycast fashion; i.e., only the source node asking for a service is specified, while it is up to the cloud control/management system to select the most suitable destination data center (DC) node. During the cloud service provisioning process, resiliency is crucial in order to guarantee continuous network operations also in the presence of failures. On the one hand, a survivability strategy needs to be able to meet the availability requirements of each specific cloud service, while on the other hand it must be efficient in using backup resources. This paper proposes a restoration-based survivability strategy, which combines the benefits of both cloud service relocation and service differentiation concepts. The former is used to enhance the restorability performance (i.e., the percentage of successfully restored cloud services) offered by restoration, while the latter ensures that critical services are given the proper consideration while backup resources are assigned. The paper proposes both an integer linear programming (ILP) formulation, which guarantees optimal results, and a heuristic, which trades the optimality of the solution achieved by the ILP for faster processing times. Simulation results show that the average service availability and restorability performance obtained by both the ILP and the heuristic are very close to that achievable using a protection-based strategy, but with the inherent benefit, in terms of efficient use of resources, offered by a restoration-based approach.
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| 5. |
- Berg, Sylvia E., 1986-, et al.
(författare)
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Heterogeneous vesiculation of 2011 El Hierro xeno-pumice revealed by X-ray computed microtomography
- 2016
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Ingår i: Bulletin of Volcanology. - : Springer Science and Business Media LLC. - 0258-8900 .- 1432-0819. ; 78:12
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Tidskriftsartikel (refereegranskat)abstract
- During the first week of the 2011 El Hierro submarine eruption, abundant light-coloured pumiceous, high-silica volcanic bombs coated in dark basanite were found floating on the sea. The composition of the light-coloured frothy material ('xeno-pumice') is akin to that of sedimentary rocks from the region, but the textures resemble felsic magmatic pumice, leaving their exact mode of formation unclear. To help decipher their origin, we investigated representative El Hierro xeno-pumice samples using X-ray computed microtomography for their internal vesicle shapes, volumes, and bulk porosity, as well as for the spatial arrangement and size distributions of vesicles in three dimensions (3D). We find a wide range of vesicle morphologies, which are especially variable around small fragments of rock contained in the xeno-pumice samples. Notably, these rock fragments are almost exclusively of sedimentary origin, and we therefore interpret them as relicts an the original sedimentary ocean crust protolith(s). The irregular vesiculation textures observed probably resulted from pulsatory release of volatiles from multiple sources during xeno-pumice formation, most likely by successive release of pore water and mineral water during incremental heating and decompression of the sedimentary protoliths.
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| 6. |
- Carracedo, Juan Carlos, et al.
(författare)
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The 2011-2012 submarine eruption off El Hierro, Canary Islands : New lessons in oceanic island growth and volcanic crisis management
- 2015
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Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 150, s. 168-200
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Tidskriftsartikel (refereegranskat)abstract
- Forty years after the eruption of the Teneguía volcano on La Palma, 1971, the last volcanic event in the Canary Islands, a submarine eruption took place in 2011 off-shore El Hierro, the smallest and youngest island of the archipelago. In this paper, we review the periods of seismic unrest leading up to the 2011–2012 El Hierro eruption, the timeline of eruptive events, the erupted products, the wider societal impacts, and the insights garnered for our understanding of ocean island growth mechanisms and hazard management. Seismic precursors allowed early detection of magmatic activity and prediction of the approximate location of the eruption. White coloured “floating stones” (“xeno-pumice”) were described within the first few days of the events, the origin of which were hotly debated because of their potential implications for the character of the eruption. Due to epistemic uncertainty derived from delayed flow of scientific information and equivocal interpretations of the “floating stones”, the El Hierro 2011–2012 events were characterised by cautious civil protection measures, which greatly impacted on the residents' lives and on the island's economy. We therefore summarise the scientific lessons learned from this most recent Canary Island eruption and discuss how emergency managers might cope with similar situations of uncertainty during future eruptive events in the region.
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| 7. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 8. |
- Natalino, Carlos, et al.
(författare)
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Optimal lifetime-aware operation of green optical backbone networks
- 2016
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Ingår i: IEEE Journal on Selected Areas in Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0733-8716 .- 1558-0008. ; 34:12, s. 3915-3926
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Tidskriftsartikel (refereegranskat)abstract
- This paper targets the lifetime-aware management of a set of optical line amplifiers (OLAs) in an optical network exploiting sleep mode (SM) in order to save energy. We first present a simple model to predict the OLA lifetime. We then provide different mixed-integer linear programming (MILP) formulations, which jointly consider energy saving and lifetime. The proposed MILP formulations are then solved on different realistic scenarios, by taking into account the spatial and temporal variations of traffic demands. Results show that our lifetime-aware approach outperforms classical energy saving ILP formulations, which instead tend to notably decrease the OLA lifetime. More important, the proposed approaches can achieve a good lifetime performance without consuming significantly more energy than purely energy-aware strategies.
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| 9. |
- Troll, Valentin, et al.
(författare)
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Nannofossils: the smoking gun for the Canarian hotspot
- 2015
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Ingår i: Geology Today. - : Wiley. - 0266-6979 .- 1365-2451. ; 31:4, s. 137-145
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Tidskriftsartikel (refereegranskat)abstract
- The origin of volcanism in the Canary Islands has been a matter of controversy for several decades. Discussions have hinged on whether the Canaries owe their origin to seafloor fractures associated with the Atlas Mountain range or to an underlying plume or hotspot of superheated mantle material. However, the debate has recently come to a conclusion following the discovery of nannofossils preserved in the products of the 2011–2012 submarine eruption at El Hierro, which tell us about the age and growth history of the western-most island of the archipelago. Light coloured, pumice-like ‘floating rocks’ were found on the sea surface during the first days of the eruption and have been shown to contain fragments of pre-island sedimentary strata. These sedimentary rock fragments were picked up by ascending magma and transported to the surface during the eruption, and remarkably retained specimens of pre-island Upper Cretaceous to Pliocene calcareous nannofossils (e.g. coccolithophores). These marine microorganisms are well known biostratigraphical markers and now provide crucial evidence that the westernmost and youngest island in the Canaries is underlain by the youngest sediment relative to the other islands in the archipelago. This finding supports an age progression for the onset of volcanism at the individual islands of the archipeligo. Importantly, as fracture-related volcanism is known to produce non-systematic age-distributions within volcanic alignments, the now-confirmed age progression corroberates to the relative motion of the African plate over an underlying mantle plume or hotspot as the cause for the present-day Canary volcanism.
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| 10. |
- Troll, Valentin R., et al.
(författare)
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Sacred ground; the Maipés necropolis of north-west Gran Canaria : the Maipés necropolis of north-west Gran Canaria
- 2019
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Ingår i: Geology Today. - : Wiley. - 0266-6979. ; 35:2, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- Gran Canaria, like most of the Canary Islands, shows evidence for young basaltic volcanism in the form of cinder cones and valley-hugging lava flows. These landforms were of no particular use to the aboriginal population, nor to the subsequent Spanish settlers, and young lava flows and lava fields are still referred to as ‘malpaÃs’ (badlands) in the Canary Islands. In north-west Gran Canaria, one such lava flow fills the bottom of a steep-sided valley, which reaches the sea at the present day village of Agaete. The lava flow erupted c. 3030 ± 90 yr bp and displays a total length of ∌ 11 km. At its distal end, just outside Agaete, it hosts one of Europe’s largest and most important pre-historic burial sites constructed of volcanic rock: the Maipés necropolis. Over 700 pre-historic tombs (or tumuli) constructed from the aa-type clinker materials have been identified on top of the valley-filling lava flow. The up to soccer-ball sized vesicular clinker fragments are sufficiently low in density to provide abundant, workable basalt blocks for the construction of the tumuli, allowing the pre-hispanic aboriginal population to create a large and magnificent ‘sacred ground’ in an otherwise barren landscape.
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| 11. |
- Troll, Valentin R., et al.
(författare)
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Volcanic particles in agriculture and gardening
- 2017
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Ingår i: Geology Today. - : Wiley. - 0266-6979 .- 1365-2451. ; 33:4, s. 148-154
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Tidskriftsartikel (refereegranskat)abstract
- Volcanic pyroclasts of small size, such as lapilli and small pumice stones, are widely used in agriculture, gardening, and for pot plants as natural inorganic mulch. The technique of using pyroclasts to enhance topsoil stems from the eighteenth century, and specifically from the ad 1730–1736 eruption on Lanzarote. Critical observations on plant development during and after the eruption showed that the vegetation died when buried under a thick layer of lapilli, but grew vigorously when covered thinly. While the agriculture of Lanzarote was restricted to cereals before the eruption, it diversified to many kinds of fruit and vegetables afterwards, including the production of the famous MalvasÃa wines in the Canaries. The population of Lanzarote doubled in the years after the eruption, from about 5000 in 1730 to near 10 000 in 1768, predominantly as a result of the higher agricultural productivity. This outcome led to widespread use of lapilli and pumice fragments throughout the islands and eventually the rest of the globe. Lapilli and pumice provide vesicle space for moisture to be retained longer within the planting soil, which can create an environment for micro-bacteria to thrive in. Through this route, nutrients from volcanic matter are transported into the surrounding soil where they become available to plant life. The detailed processes that operate within the pyroclasts are less well understood, such as the breakdown of nutrients from the rock matrix and transport into the soil by biological action. Further studies promise significant potential to optimize future agricultural efforts, particularly in otherwise arid areas of the globe.
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| 12. |
- Wiseman, Frances K, et al.
(författare)
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Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP.
- 2018
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 141:8, s. 2457-2474
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Tidskriftsartikel (refereegranskat)abstract
- Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. However, whether triplication of other chromosome 21 genes influences disease pathogenesis in the context of Down syndrome is unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes other than APP increases amyloid-β aggregation, deposition of amyloid-β plaques and worsens associated cognitive deficits. This indicates that triplication of chromosome 21 genes other than APP is likely to have an important role to play in Alzheimer's disease pathogenesis in individuals who have Down syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid-β aggregation correlates with an unexpected shift in soluble amyloid-β 40/42 ratio. This alteration in amyloid-β isoform ratio occurs independently of a change in the carboxypeptidase activity of the γ-secretase complex, which cleaves the peptide from APP, or the rate of extracellular clearance of amyloid-β. These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.
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| 13. |
- Zaczek, Kirsten, et al.
(författare)
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Nannofossils in 2011 El Hierro eruptive products reinstate plume model for Canary Islands
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 7945-
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Tidskriftsartikel (refereegranskat)abstract
- The origin and life cycle of ocean islands have been debated since the early days of Geology. In the case of the Canary archipelago, its proximity to the Atlas orogen led to initial fracture-controlled models for island genesis, while later workers cited a Miocene-Quaternary east-west age-progression to support an underlying mantle-plume. The recent discovery of submarine Cretaceous volcanic rocks near the westernmost island of El Hierro now questions this systematic age-progression within the archipelago. If a mantle-plume is indeed responsible for the Canaries, the onshore volcanic age-progression should be complemented by progressively younger pre-island sedimentary strata towards the west, however, direct age constraints for the westernmost pre-island sediments are lacking. Here we report on new age data obtained from calcareous nannofossils in sedimentary xenoliths erupted during the 2011 El Hierro events, which date the sub-island sedimentary rocks to between late Cretaceous and Pliocene in age. This age-range includes substantially younger pre-volcanic sedimentary rocks than the Jurassic to Miocene strata known from the older eastern islands and now reinstate the mantle-plume hypothesis as the most plausible explanation for Canary volcanism. The recently discovered Cretaceous submarine volcanic rocks in the region are, in turn, part of an older, fracture-related tectonic episode.
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