1. |
- Aljabali, Alaa A. A., et al.
(författare)
-
The viral capsid as novel nanomaterials for drug delivery
- 2021
-
Ingår i: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 7:9
-
Forskningsöversikt (refereegranskat)abstract
- The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging. Lay abstract: The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging. Here we performed a comprehensive database search to review findings in this area, demonstrating that viral nanostructures possess unique properties that make them ideal for applications in diagnostics, cell labeling, contrasting agents and drug delivery structures.
|
|
2. |
- Bussel, James, et al.
(författare)
-
Mechanisms and therapeutic prospects of thrombopoietin receptor agonists
- 2019
-
Ingår i: Seminars in Hematology. - : Elsevier BV. - 0037-1963. ; 56:4, s. 262-278
-
Forskningsöversikt (refereegranskat)abstract
- The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is approved for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and in the USA for the first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Eltrombopag has also shown efficacy in several other disease settings, for example, chemotherapy-induced thrombocytopenia, selected inherited thrombocytopenias, and myelodysplastic syndromes. While both TPO receptor agonists stimulate TPO receptor signaling and enhance megakaryopoiesis, their vastly different biochemical structures bestow upon them markedly different molecular and functional properties. Here, we review and discuss results from preclinical and clinical studies on the functional and molecular mechanisms of action of this new class of drug.
|
|
3. |
- Dickinson, Michael, et al.
(författare)
-
Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia
- 2018
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 132:25, s. 2629-2638
-
Tidskriftsartikel (refereegranskat)abstract
- Azacitidine treatment of myelodysplastic syndromes (MDSs) generally exacerbates thrombocytopenia during the first treatment cycles. A Study of Eltrombopag in Myelodysplastic Syndromes Receiving Azacitidine (SUPPORT), a phase 3, randomized, double-blind, placebo-controlled study, investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. International Prognostic Scoring System intermediate-1, intermediate-2, or high-risk MDS patients with baseline platelets <75 3 10(9)/L were randomized 1: 1 to eltrombopag (start, 200 mg/d [East Asians, 100 mg/d], maximum, 300 mg/d [East Asians, 150 mg/d]) or placebo, plus azacitidine (75 mg/m2 subcutaneously once daily for 7 days every 28 days). The primary end point was the proportion of patients platelet transfusion-free during cycles 1 through 4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely because efficacy outcomes crossed the predefined futility threshold and for safety reasons. At termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary end point. Overall response (International Working Group criteria; complete, marrow, or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment. There was no difference in hematologic improvement in any cell lineage between the 2 arms. There was no improvement in overall or progression-free survival. Adverse events with >= 10% occurrence in the eltrombopag vs placebo arm were febrile neutropenia and diarrhea. Compared with azacitidine alone, eltrombopag plus azacitidine worsened platelet recovery, with lower response rates and a trend toward increased progression to acute myeloid leukemia. This trial was registered at www.clinicaltrials.govas# NCT02158936.
|
|
4. |
- Islam, Shadli, et al.
(författare)
-
Ab-initio Calculation of Nonlinear Optical Susceptibilities in Germanium Quantum Dots
- 2019
-
Ingår i: 2018 IEEE 13TH NANOTECHNOLOGY MATERIALS AND DEVICES CONFERENCE (NMDC). - 2378-377X. - 9781538610169 ; , s. 113-116
-
Konferensbidrag (refereegranskat)abstract
- Using Time Independent Density Functional Theory (TIDFT) implemented in SIESTA (R) we calculated the 2nd order and 3rd order nonlinear optical susceptibilities of small Germanium Quantum Dots (GeQD). We observe that the symmetry breaking due to surface termination enhances chi((2)) up to 299.1 pm/V which promises a strong Second Harmonic Generation (SHG) in GeQDs. Diagonal components for chi((2)) tensor are 52.5, 11.2, 299.1 pm/V, for xxx, yyy and zzz, respectively. The 3rd order susceptibility, chi((3)), is within the range of (0.2-0.4) x 10(-18) m(2)/V-2 which is close to the reported experimental values of bulk Germanium. This study suggests possibilities of enhancing SHG in GeQDs through symmetry breaking via strain and surface termination/reconstruction as well as suitability of this fast and less-computationally intensive Density Functional Theory (DFT)-based method in predicting nonlinear optical susceptibilities of nano structures.
|
|
5. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
6. |
- Kinyoki, DK, et al.
(författare)
-
Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
-
Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
-
Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
|
|
7. |
- Kumar, Amit, et al.
(författare)
-
Anticipating the impact of glaciers, landslides and extreme weather events on vulnerable hydropower projects and the development of an integrated multi-hazard warning system (IMWS)
- 2024
-
Ingår i: Sustainable Energy Technologies and Assessments. - 2213-1388. ; 65
-
Tidskriftsartikel (refereegranskat)abstract
- The Himalayan river basins offer great potential for hydropower development, but they are also vulnerable to various hazards such as debris flows, landslides, flash floods, glacial lake outburst floods (GLOFs), and landslide lake outburst floods (LLOFs). Despite the regional and global significance of these hazards, there is a lack of information and data on different aspects, including meteorology, hydrology, geology, and seismology. Many hazards often go unnoticed or receive little attention until they start affecting humans and their activities like damage to buildings, infrastructure, and other human-made structures. It is important to recognize that hazards can have severe and long-lasting impacts on society, even when they do not directly affect humans. For example, flash floods can disrupt ecosystems, destroy habitats, and threaten biodiversity and the complexity of climatic influences on both regional and local scales cannot be overlooked. Therefore, we highlight the importance of basin-wise and basin-wide continuous long-term monitoring in the Himalaya. It is also recommended that the highest hydropower projects in the basins should have their network of hydro-meteorological observatories at different altitudes with a provision of real-time data transmission and deployment of a multi-hazard warning system (IMWS) for flash floods.
|
|
8. |
- Marques Ramos, Pedro, et al.
(författare)
-
Next-generation sequencing of baseline genetic mutations and outcomes of eltrombopag and azacitidine therapy in patients with myelodysplastic syndromes and thrombocytopenia : Data from the SUPPORT clinical trial
- 2023
-
Ingår i: eJHaem. - : John Wiley & Sons. - 2688-6146. ; 4:3, s. 876-881
-
Tidskriftsartikel (refereegranskat)abstract
- Eltrombopag has been previously shown to be effective in reversing azacitidine-mediated thrombocytopenia. This was further investigated in the SUPPORT trial, a phase III study assessing the efficacy/safety of eltrombopag plus azacitidine in patients with intermediate- to high-risk myelodysplastic syndromes and thrombocytopenia. The results did not support a clinical benefit for the addition of eltrombopag to azacitidine. We investigated if the somatic mutational profiles in the patient cohort were associated with treatment outcomes. Based on the available data, we observed no imbalance in the mutational profiles between treatment arms or a clear association between identified somatic mutations and clinical outcomes.
|
|
9. |
- Patwardhan, Amit, et al.
(författare)
-
A Survey on Predictive Maintenance Through Big Data
- 2016
-
Ingår i: Current Trends in Reliability, Availability, Maintainability and Safety. - Cham : Encyclopedia of Global Archaeology/Springer Verlag. - 9783319235967 - 9783319235974 ; , s. 437-445
-
Konferensbidrag (refereegranskat)abstract
- Modern manufacturing systems use thousands of sensors retrieving information at hundreds to thousands of samples per second. The real time data being generated is mostly used for monitoring the processes and the equipment condition. Data processing techniques applied to this data to detect anomalies and thus applying preventive maintenance have been used in the industry. Currently available technologies which were developed during the last two decade for scanning the Internet and providing computational services, working at very large scale can be re-targeted to fulfil the requirements of maintenance of complex systems. These systems can support storage and processing of current as well as historical data. Ability to access and process these large data sets will lead from preventive to predictive maintenance and eventually to smart manufacturing..
|
|
10. |
|
|
11. |
- Riihimaki, Laura D., et al.
(författare)
-
Ocean surface radiation measurement best practices
- 2024
-
Ingår i: FRONTIERS IN MARINE SCIENCE. - 2296-7745. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Ocean surface radiation measurement best practices have been developed as a first step to support the interoperability of radiation measurements across multiple ocean platforms and between land and ocean networks. This document describes the consensus by a working group of radiation measurement experts from land, ocean, and aircraft communities. The scope was limited to broadband shortwave (solar) and longwave (terrestrial infrared) surface irradiance measurements for quantification of the surface radiation budget. Best practices for spectral measurements for biological purposes like photosynthetically active radiation and ocean color are only mentioned briefly to motivate future interactions between the physical surface flux and biological radiation measurement communities. Topics discussed in these best practices include instrument selection, handling of sensors and installation, data quality monitoring, data processing, and calibration. It is recognized that platform and resource limitations may prohibit incorporating all best practices into all measurements and that spatial coverage is also an important motivator for expanding current networks. Thus, one of the key recommendations is to perform interoperability experiments that can help quantify the uncertainty of different practices and lay the groundwork for a multi-tiered global network with a mix of high-accuracy reference stations and lower-cost platforms and practices that can fill in spatial gaps.
|
|
12. |
- Shiri, Daryoush, 1975, et al.
(författare)
-
Gunn-Hilsum Effect in Mechanically Strained Silicon Nanowires: Tunable Negative Differential Resistance
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Gunn (or Gunn-Hilsum) Effect and its associated negative differential resistivity (NDR) emanates from transfer of electrons between two different energy subbands. This effect was observed in semiconductors like GaAs which has a direct bandgap of very low effective mass and an indirect subband of high effective mass which lies ~300 meV above the former. In contrast to GaAs, bulk silicon has a very high energy spacing (~1 eV) which renders the initiation of transfer-induced NDR unobservable. Using Density Functional Theory (DFT), semi-empirical 10 orbital (sp 3 d 5 s ∗ ) Tight Binding and Ensemble Monte Carlo (EMC) methods we show for the first time that (a) Gunn Effect can be induced in silicon nanowires (SiNW) with diameters of 3.1 nm under +3% strain and an electric field of 5000 V/cm, (b) the onset of NDR in the I-V characteristics is reversibly adjustable by strain and (c) strain modulates the resistivity by a factor 2.3 for SiNWs of normal I-V characteristics i.e. those without NDR. These observations are promising for applications of SiNWs in electromechanical sensors and adjustable microwave oscillators. It is noteworthy that the observed NDC is different in principle from Esaki-Diode and Resonant Tunneling Diodes (RTD) in which NDR originates from tunneling effect.
|
|
13. |
- Verma, Amit, et al.
(författare)
-
Low-Temperature Effects on Electron Transport in Small-Diameter Silicon Nanowire
- 2023
-
Ingår i: 2023 IEEE Nanotechnology Materials and Devices Conference (NMDC). - 9798350335460 ; , s. 31-34
-
Konferensbidrag (refereegranskat)abstract
- We report on modeling studies on the effect of very low temperatures (4K-77K) on the behavior of electron transport in a [110] axially aligned, 1.3 nm diameter unstrained silicon nanowire (SiNW). A sp3d5s * tight-binding scheme is used to calculate the band structure within an Ensemble Monte Carlo simulation. Electron scattering occurs through bulk-acoustic and bulk-optical phonons and includes intra-subband and inter-subband events. A comparison with room temperature (300K) shows that at lower temperatures, average electron steady-state drift velocity increases by 2 or more times at relatively moderate electric fields. Transient average electron velocity also shows a more pronounced streaming motion. This is attributed to an overall decrease in electron-phonon scattering rates with temperature.
|
|