| 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. |
- Frey, B. N., et al.
(författare)
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Cooling Yb-Doped Silica Fibers and Fiber Lasers with Anti-Stokes Pumping
- 2023
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9781510659797
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Konferensbidrag (refereegranskat)abstract
- Optical cooling in Yb-doped silica fibers using anti-Stokes fluorescence has become a subject of great interest in the fiber laser community. This paper provides an update on the development of silica fibers designed specifically to enhance their cooling properties. This growing list includes a new, nearly single-mode fiber with a borophosphosilicate core that produced –65 mK of cooling with only 260 mW of 1040-nm pump power. The silica compositions that have now been successfully cooled at atmospheric pressure by anti-Stokes fluorescence by our team include aluminosilicate, aluminofluorosilicate, borophosphosilicate, and aluminosilicate doped with one of three different alkali-earth nanoparticles (Ba, Sr, and Ca). By fitting the measured temperature dependence of the cooled fiber on pump power, two key parameters that control the degree of cooling are inferred, namely the critical quenching concentration and the absorptive loss due to impurities. The inferred values compiled for the fibers that cooled indicate that the extracted heat is highest when the Yb concentration is 2 wt.% or more (to maximize heat extraction), the Al concentration is ~0.8 wt.% or greater (to reduce quenching), and the absorptive loss is below approximately 15 dB/km, and ideally below 5 dB/km (to minimize heating due to pump absorption). Only two of the reported fibers, an LaF3-doped and an LuF3-doped nanoparticle fiber, did not cool, because their Yb and Al concentrations were not sufficiently high. This analysis shows that through careful composition control (especially the Al and Yb concentrations) and minimization of the OH contamination, a new generation of Yb-doped silica fibers is emerging with higher Yb concentrations, greater resistance to quenching, and lower residual loss than commercial Yb-doped fibers. They can be expected to have a significant impact not only on optically cooled devices but also on a much broader range of fiber lasers and amplifiers.
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| 3. |
- Balliu, Enkeleda, PhD student, et al.
(författare)
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Improved Closed-Loop Slow-Light Temperature Sensor With Millidegree Resolution for Laser Cooling
- 2023
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Ingår i: Proceedings - 28th International Conference on Optical Fiber Sensors, OFS 2023. - : Optica Publishing Group.
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Konferensbidrag (refereegranskat)abstract
- For applications such as laser cooling of doped fibers, where it is critical to measure accurately the temperature of a cooled fiber that is very close to room temperature, it is paramount to develop a reliable, very short (mm) fiber temperature sensor with millikelvin resolution and very little drift. We report a second generation of a unique slow-light fiber Bragg grating (FBG) temperature sensor that meets these stringent requirements. Experiments and modeling establish that its temperature response depends only on well-known material constants of the silica FBG and the response of the probe laser's wavelength controller. The response is independent of the linewidth of the slow-light resonance, hence different FBGs and/or resonances have the exact same response. Examples of measured cooling in optically pumped Yb-doped fibers show that more reliable thermal contact with the cooled fiber is obtained by wrapping the FBG and the cooled fiber.
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| 4. |
- Balliu, Brunilda, et al.
(författare)
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Genetic regulation of gene expression and splicing during a 10-year period of human aging
- 2019
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age.Results: We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging at a population and individual level. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age. We identify 1291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories. Further, we observe a strong correlation of genetic effects on expression and splicing between the two ages, with a small subset of tested genes showing a reduction in genetic associations with expression and splicing in older age.Conclusions: These findings demonstrate that, although the transcriptome and its genetic regulation is mostly stable late in life, a small subset of genes is dynamic and is characterized by a reduction in genetic regulation, most likely due to increasing environmental variance with age.
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| 5. |
- Balliu, Enkeleda, PhD student, et al.
(författare)
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High-efficiency radiation-balanced Yb-doped silica fiber laser with 200-mW output
- 2024
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Ingår i: Optics Letters. - : Optica Publishing Group. - 0146-9592 .- 1539-4794. ; 49:8, s. 2021-2024
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Tidskriftsartikel (refereegranskat)abstract
- The focus of this study was the development of a second generation of fiber lasers internally cooled by anti-Stokes fluorescence. The laser consisted of a length of a single-mode fiber spliced to fiber Bragg gratings to form the optical resonator. The fiber was single-moded at the pump (1040 nm) and signal (1064 nm) wavelengths. Its core was heavily doped with Yb, in the initial form of CaF2 nanoparticles, and co-doped with Al to reduce quenching and improve the cooling efficiency. After optimizing the fiber length (4.1 m) and output-coupler reflectivity (3.3%), the fiber laser exhibited a threshold of 160 mW, an optical efficiency of 56.8%, and a radiation-balanced output power (no net heat generation) of 192 mW. On all three metrics, this performance is significantly better than the only previously reported radiation-balanced fiber laser, which is even more meaningful given that the small size of the single-mode fiber core (7.8-µm diameter). At the maximum output power (∼2 W), the average fiber temperature was still barely above room temperature (428 mK). This work demonstrates that with anti-Stokes pumping, it is possible to induce significant gain and energy storage in a small-core Yb-doped fiber while keeping the fiber cool.
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| 6. |
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| 7. |
- Schoepe, Daniel, 1989, et al.
(författare)
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Explicit Secrecy: A Policy for Taint Tracking
- 2016
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Ingår i: 1st IEEE European Symposium on Security and Privacy (Euro S&P), Saarbruecken, Germany, Mar 21-24, 2016. - 9781509017522 ; , s. 15-30
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Konferensbidrag (refereegranskat)abstract
- Taint tracking is a popular security mechanism for tracking data-flow dependencies, both in high-level languages and at the machine code level. But despite the many taint trackers in practical use, the question of what, exactly, tainting means-what security policy it embodies-remains largely unexplored. We propose explicit secrecy, a generic framework capturing the essence of explicit flows, i.e., the data flows tracked by tainting. The framework is semantic, generalizing previous syntactic approaches to formulating soundness criteria of tainting. We demonstrate the usefulness of the framework by instantiating it with both a simple high-level imperative language and an idealized RISC machine. To further understanding of what is achieved by taint tracking tools, both dynamic and static, we obtain soundness results with respect to explicit secrecy for the tainting engine cores of a collection of popular dynamic and static taint trackers.
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