| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Feroci, M., et al.
(författare)
-
The Large Observatory for X-ray Timing (LOFT)
- 2012
-
Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
-
Tidskriftsartikel (refereegranskat)abstract
- High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
|
|
| 6. |
- Beck, S., et al.
(författare)
-
The Open Innovation in Science research field: a collaborative conceptualisation approach
- 2022
-
Ingår i: Industry and Innovation. - : Informa UK Limited. - 1366-2716 .- 1469-8390. ; 29:2, s. 136-185
-
Tidskriftsartikel (refereegranskat)abstract
- Openness and collaboration in scientific research are attracting increasing attention from scholars and practitioners alike. However, a common understanding of these phenomena is hindered by disciplinary boundaries and disconnected research streams. We link dispersed knowledge on Open Innovation, Open Science, and related concepts such as Responsible Research and Innovation by proposing a unifying Open Innovation in Science (OIS) Research Framework. This framework captures the antecedents, contingencies, and consequences of open and collaborative practices along the entire process of generating and disseminating scientific insights and translating them into innovation. Moreover, it elucidates individual-, team-, organisation-, field-, and society-level factors shaping OIS practices. To conceptualise the framework, we employed a collaborative approach involving 47 scholars from multiple disciplines, highlighting both tensions and commonalities between existing approaches. The OIS Research Framework thus serves as a basis for future research, informs policy discussions, and provides guidance to scientists and practitioners.
|
|
| 7. |
- Arabuli, Lili, et al.
(författare)
-
Co-aggregation of S100A9 with DOPA and cyclen-based compounds manifested in amyloid fibril thickening without altering rates of self-assembly
- 2021
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:16
-
Tidskriftsartikel (refereegranskat)abstract
- The amyloid cascade is central for the neurodegeneration disease pathology, including Alzheimer’s and Parkinson’s, and remains the focus of much current research. S100A9 protein drives the amyloid-neuroinflammatory cascade in these diseases. DOPA and cyclen-based compounds were used as amyloid modifiers and inhibitors previously, and DOPA is also used as a precursor of dopamine in Parkinson’s treatment. Here, by using fluorescence titration experiments we showed that five selected ligands: DOPA-D-H-DOPA, DOPA-H-H-DOPA, DOPA-D-H, DOPA-cyclen, and H-E-cyclen, bind to S100A9 with apparent Kd in the sub-micromolar range. Ligand docking and molecular dynamic simulation showed that all compounds bind to S100A9 in more than one binding site and with different ligand mobility and H-bonds involved in each site, which all together is consistent with the apparent binding determined in fluorescence experiments. By using amyloid kinetic analysis, monitored by thioflavin-T fluorescence, and AFM imaging, we found that S100A9 co-aggregation with these compounds does not hinder amyloid formation but leads to morphological changes in the amyloid fibrils, manifested in fibril thickening. Thicker fibrils were not observed upon fibrillation of S100A9 alone and may influence the amyloid tissue propagation and modulate S100A9 amyloid assembly as part of the amyloid-neuroinflammatory cascade in neurodegenerative diseases.
|
|
| 8. |
- Chaudhary, Himanshu, et al.
(författare)
-
Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases
- 2021
-
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:23, s. 26721-26734
-
Tidskriftsartikel (refereegranskat)abstract
- Pro-inflammatory and amyloidogenic S100A9 protein is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases. Polyoxometalates (POMs) constitute a diverse group of nanomaterials, which showed potency in amyloid inhibition. Here, we have demonstrated that two selected nanosized niobium POMs, Nb10 and TiNb9, can act as potent inhibitors of S100A9 amyloid assembly. Kinetics analysis based on ThT fluorescence experiments showed that addition of either Nb10 or TiNb9 reduces the S100A9 amyloid formation rate and amyloid quantity. Atomic force microscopy imaging demonstrated the complete absence of long S100A9 amyloid fibrils at increasing concentrations of either POM and the presence of only round-shaped and slightly elongated aggregates. Molecular dynamics simulation revealed that both Nb10 and TiNb9 bind to native S100A9 homo-dimer by forming ionic interactions with the positively charged Lys residue-rich patches on the protein surface. The acrylamide quenching of intrinsic fluorescence showed that POM binding does not perturb the Trp 88 environment. The far and near UV circular dichroism revealed no large-scale perturbation of S100A9 secondary and tertiary structures upon POM binding. These indicate that POM binding involves only local conformational changes in the binding sites. By using intrinsic and 8-anilino-1-naphthalene sulfonate fluorescence titration experiments, we found that POMs bind to S100A9 with a Kd of ca. 2.5 μM. We suggest that the region, including Lys 50 to Lys 54 and characterized by high amyloid propensity, could be the key sequences involved in S1009 amyloid self-assembly. The inhibition and complete hindering of S100A9 amyloid pathways may be used in the therapeutic applications targeting the amyloid-neuroinflammatory cascade in neurodegenerative diseases.
|
|
| 9. |
- Isakov, V., et al.
(författare)
-
Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden
- 2019
-
Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 51:2, s. 131-139
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. Methods: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naive or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Results: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. Conclusion: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated.
|
|
| 10. |
- Romanova, E. S., et al.
(författare)
-
Cause of death based on systematic post-mortem studies in patients with positive SARS-CoV-2 tissue PCR during the COVID-19 pandemic
- 2021
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 655-665
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). Methods: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. Results: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. Conclusions: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.
|
|
