| 1. |
|
|
| 2. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Hait, A. S., et al.
(författare)
-
Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
- 2020
-
Ingår i: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:54
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
|
|
| 4. |
- Edmund, J. M., et al.
(författare)
-
Optically stimulated luminescence from Al2O3 : C irradiated with 10-60 MeV protons
- 2007
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 580:1, s. 210-213
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the potential use of Al2O3:C for medical proton dosimetry. Detector crystals coupled to fiber-optic cables were irradiated in proton beams with energies from 10 to 60 MeV. The key finding is that the initial intensity of the optically stimulated luminescence (OSL) signal is energy independent for small detectors (<0.5mm) and relatively small doses (<0.3Gy). This feature is related to the supralinearity of the detectors dose-response to low linear energy transfer (LET) radiation. The results show that our system can be used in medical proton dosimetry without LET-dependent correction factors in the dose and energy interval investigated. (c) 2007 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Ong, Ken K., et al.
(författare)
-
Genetic variation in LIN28B is associated with the timing of puberty
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:6, s. 729-733
-
Tidskriftsartikel (refereegranskat)abstract
- The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing(2), as the first genetic determinant regulating the timing of human pubertal growth and development.
|
|
| 6. |
|
|
| 7. |
- Andersen, C. E., et al.
(författare)
-
Medical proton dosimetry using radioluminescence from aluminium oxide crystals attached to optical-fiber cables
- 2007
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576 .- 0167-5087. ; 580:1, s. 466-468
-
Tidskriftsartikel (refereegranskat)abstract
- The prime objective of this study is to investigate if radioluminescence (RL) from carbon-doped aluminum oxide (Al2O3:C) crystals potentially can be used for absorbed dose-rate measurements during proton radiotherapy. The RL from two separate (2 mg) Al2O3:C crystals attached to optical-fiber cables were recorded during irradiations in water in a 175 MeV clinical proton beam. The RL response for low-LET protons in the plateau region of the Bragg curve was found to closely resemble that observed for a clinical 6 MV X-ray beam. An identical response was found in the Bragg peak (where the dose-averaged LET is about 4 keV/mu m) for absorbed doses less than 0.3 Gy. For doses in the range of 0.3-3Gy, we observed a significant decrease in luminescence efficiency with LET. At 3 Gy, the luminescence efficiency was about 60% in the Bragg-peak region. The study implies that the RL-signal from Al2O3:C could potentially be suitable for medical proton dosimetry in the 0-0.3 Gy range even without any LET-dependent correction factors.
|
|
| 8. |
- Andersen, Sören M., et al.
(författare)
-
A scalable route to 5-substituted 3-isoxazolol fibrinolysis inhibitor AZD6564
- 2014
-
Ingår i: Organic Process Research & Development. - : American Chemical Society (ACS). - 1083-6160 .- 1520-586X. ; 18:8, s. 952-959
-
Tidskriftsartikel (refereegranskat)abstract
- A practical and chromatography-free multikilogram synthesis of a 3-isoxazolol containing antifibrinolytic agent, AZD6564, has been developed in eight steps and 7% overall yield starting from methyl 2-chloroisonicotinate. Highlights in the synthesis are a Negishi coupling and an enzymatic resolution of a racemic ester.
|
|
| 9. |
- Dyreborg, Karen, et al.
(författare)
-
Migration of the uncemented Echo Bi-Metric and Bi-Metric THA stems : a randomized controlled RSA study involving 62 patients with 24-month follow-up
- 2020
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:6, s. 693-698
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Despite the good results after total hip arthroplasty (THA), new implants are continuously being developed to improve durability. The Echo Bi-Metric (EBM) THA stem is the successor to the Bi-Metric (BM) THA stem. The EBM stem includes many of the features of the BM stem, but minor changes in the design might improve the clinical performance. We compared the migration behavior with radiostereometric analysis (RSA) of the EBM stem and the BM stem at 24 months and evaluated the clinical outcome. Patients and methods — We randomized 62 patients with osteoarthritis (mean age 64 years, female/male 28/34) scheduled for an uncemented THA to receive either an EBM or a BM THA stem. We performed RSA within 1 week after surgery and at 3, 6, 12, and 24 months. The clinical outcome was evaluated using Harris Hip Score (HHS) and Oxford Hip Score (OHS). Results — At 24 months, we found no statistically significant differences in migration between the two implants. During the first 3 months both the EBM and the BM stems showed visible subsidence (2.5 mm and 2.2 mm respectively), and retroversion (2.5° and 2.2° respectively), but after 3 months this stabilized. The expected increase in HHS and OHS was similar between the groups. Interpretation — The EBM stem showed a migration at 24 months not different from the BM stem, and both stems display satisfying clinical results.
|
|
| 10. |
- Karlsson, Staffan, et al.
(författare)
-
An Enantioselective Hydrogenation of an Alkenoic Acid as a Key Step in the Synthesis of AZD2716
- 2016
-
Ingår i: Organic Process Research & Development. - : American Chemical Society (ACS). - 1083-6160 .- 1520-586X. ; 20:2, s. 262-269
-
Tidskriftsartikel (refereegranskat)abstract
- A classical resolution of a racemic carboxylic acid through salt formation and an asymmetric hydrogenation of an α,β-unsaturated carboxylic acid were investigated in parallel to prepare an enantiomerically pure alkanoic acid used as a key intermediate in the synthesis of an antiplaque candidate drug. After an extensive screening of rhodium- and ruthenium-based catalysts, we developed a rhodium-catalyzed hydrogenation that gave the alkanoic acid with 90% ee, and after a subsequent crystallization with (R)-1-phenylethanamine, the ee was enriched to 97%. The chiral acid was then used in sequential Negishi and Suzuki couplings followed by basic hydrolysis of a nitrile to an amide to give the active pharmaceutical ingredient in 22% overall yield.
|
|
