| 1. |
|
|
| 2. |
- Abellán, C., et al.
(författare)
-
Challenging Local Realism with Human Choices
- 2018
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
-
Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
|
|
| 3. |
- Liu, P., et al.
(författare)
-
Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis
- 2017
-
Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 24:4, s. 672-682
-
Tidskriftsartikel (refereegranskat)abstract
- During osteoporosis bone formation by osteoblasts is reduced and/or bone resorption by osteoclasts is enhanced. Currently, only a few factors have been identified in the regulation of bone integrity by osteoblast-derived osteocytes. In this study, we show that specific disruption of menin, encoded by multiple endocrine neoplasia type 1 (Men1), in osteoblasts and osteocytes caused osteoporosis despite the preservation of osteoblast differentiation and the bone formation rate. Instead, an increase in osteoclast numbers and bone resorption was detected that persisted even when the deletion of Men1 was restricted to osteocytes. We demonstrate that isolated Men1-deficient osteocytes expressed numerous soluble mediators, such as C-X-C motif chemokine 10 (CXCL10), and that CXCL10-mediated osteoclastogenesis was reduced by CXCL10-neutralizing antibodies. Collectively, our data reveal a novel role for Men1 in osteocyte-osteoclast crosstalk by controlling osteoclastogenesis through the action of soluble factors. A role for Men1 in maintaining bone integrity and thereby preventing osteoporosis is proposed.
|
|
| 4. |
|
|
| 5. |
- Carreras, A., et al.
(författare)
-
In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model
- 2019
-
Ingår i: Bmc Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target disease alleles.ResultsTo address the lack of validated models to test the safety and efficacy of techniques to target human PCSK9, we generated a liver-specific human PCSK9 knock-in mouse model (hPCSK9-KI). We showed that plasma concentrations of total cholesterol were higher in hPCSK9-KI than in wildtype mice and increased with age. Treatment with evolocumab, a monoclonal antibody that targets human PCSK9, reduced cholesterol levels in hPCSK9-KI but not in wildtype mice, showing that the hypercholesterolemic phenotype was driven by overexpression of human PCSK9. CRISPR-Cas9-mediated genome editing of human PCSK9 reduced plasma levels of human and not mouse PCSK9, and in parallel reduced plasma concentrations of total cholesterol; genome editing of mouse Pcsk9 did not reduce cholesterol levels. Base editing using a guide RNA that targeted human and mouse PCSK9 reduced plasma levels of human and mouse PCSK9 and total cholesterol. In our mouse model, base editing was more precise than genome editing, and no off-target editing nor chromosomal translocations were identified.ConclusionsHere, we describe a humanized mouse model with liver-specific expression of human PCSK9 and a human-like hypercholesterolemia phenotype, and demonstrate that this mouse can be used to evaluate antibody and gene editing-based (genome and base editing) therapies to modulate the expression of human PCSK9 and reduce cholesterol levels. We predict that this mouse model will be used in the future to understand the efficacy and safety of novel therapeutic approaches for hypercholesterolemia.
|
|
| 6. |
|
|
| 7. |
- Knoll, Fabien, et al.
(författare)
-
A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds
- 2018
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.
|
|
| 8. |
- Lucas, P., et al.
(författare)
-
Development of the neurorobotic mouse
- 2019
-
Ingår i: 2019 IEEE International Conference on Cyborg and Bionic Systems, CBS 2019. - : Institute of Electrical and Electronics Engineers Inc.. ; , s. 299-304
-
Konferensbidrag (refereegranskat)abstract
- In this paper we describe the NeuroRobotic Mouse (NeRmo) a low-cost, modular bio mimetic robot, mimicking the actuation and walking behaviour of a common mouse (Mus musculus). This latest version has 13 Degrees of Freedom with 21 tendon driven joints and can be controlled in both open and closed loop. It is capable of different gaits as well as keeping the body upright when in a sitting position. The robot includes joint position sensors, pressure sensors on the soles of the feet as well as two cameras in the head. As the design of this robotic platform was inspired by detailed observations of the biomechanics of mice and rats, it can be used in motion research using animal data as am element of comparison, or even as actuation input.
|
|
| 9. |
|
|
