| 1. |
- Liwing, Johan, et al.
(författare)
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Improved survival in myeloma patients : starting to close in on the gap between elderly patients and a matched normal population
- 2014
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 164:5, s. 684-693
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Tidskriftsartikel (refereegranskat)abstract
- The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2.8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4.9 years) compared to conventional treatment (2.3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6.9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.
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| 2. |
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| 3. |
- Ahlberg, Simon, et al.
(författare)
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An information fusion demonstrator for tactical intelligence processing in network-based defense
- 2007
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Ingår i: Information Fusion. - : Elsevier BV. - 1566-2535 .- 1872-6305. ; 8:1, s. 84-107
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Defence Research Agency (FOI) has developed a concept demonstrator called the Information Fusion Demonstrator 2003 (IFD03) for demonstrating information fusion methodology suitable for a future Network Based Defense (NBD) C4ISR system. The focus of the demonstrator is on real-time tactical intelligence processing at the division level in a ground warfare scenario. The demonstrator integrates novel force aggregation, particle filtering, and sensor allocation methods to create, dynamically update, and maintain components of a tactical situation picture. This is achieved by fusing physically modelled and numerically simulated sensor reports from several different sensor types with realistic a priori information sampled from both a high-resolution terrain model and an enemy organizational and behavioral model. This represents a key step toward the goal of creating in real time a dynamic, high fidelity representation of a moving battalion-sized organization, based on sensor data as well as a priori intelligence and terrain information, employing fusion, tracking, aggregation, and resource allocation methods all built on well-founded theories of uncertainty. The motives behind this project, the fusion methods developed for the system, as well as its scenario model and simulator architecture are described. The main services of the demonstrator are discussed and early experience from using the system is shared.
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| 4. |
- Ahlberg, Simon, et al.
(författare)
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The IFD03 information fusion demonstrator
- 2004
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Ingår i: Proceedings of the Seventh International Conference on Information Fusion, FUSION 2004. - 917056115X ; , s. 936-943
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Konferensbidrag (refereegranskat)abstract
- The paper discusses a recently developed demonstrator system where new ideas in tactical information fusion may be tested and demonstrated. The main services of the demonstrator are discussed, and essential experience from the use and development of the system is shared.
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| 5. |
- Eriksson, Henrik, et al.
(författare)
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Sorting a bridge hand
- 2001
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Ingår i: Discrete Mathematics. - 0012-365X .- 1872-681X. ; 241:1-3, s. 289-300
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Tidskriftsartikel (refereegranskat)abstract
- Sorting a permutation by block moves is a task that every bridge player has to solve every time she picks up a new hand of cards. It is also a problem for the computational biologist, for block moves are a fundamental type of mutation that can explain why genes common to two species do not occur in the same order in the chromosome, It is not known whether there exists an optimal sorting procedure running in polynomial time. Bafna and Pevzner gave a polynomial time algorithm that sorts any permutation of length n in at most 3n/4 moves. Our new algorithm improves this to [(2n - 2)/3] for n greater than or equal to 9. For the reverse permutation, we give an exact expression for the number of moves needed, namely [(n + 1)/2]. Computations of Bafha and Pevzner up to n = 10 seemed to suggest that this is the worst case; but as it turns out, a first counterexample occurs for n = 13, i.e. the bridge player's case. Professional card players never sort by rank, only by suit. For this case, we give a complete answer to the optimal sorting problem.
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| 6. |
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| 7. |
- Giang, Kim Anh, et al.
(författare)
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Affibody-based hBCMA x CD16 dual engagers for NK cell-mediated killing of multiple myeloma cells
- 2023
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Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 77, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- We describe the development and characterization of the (to date) smallest Natural Killer (NK) cell re-directing human B Cell Maturation Antigen (hBCMA) x CD16 dual engagers for potential treatment of multiple myeloma, based on combinations of small 58 amino acid, non-immunoglobulin, affibody affinity proteins. Affibody molecules to human CD16a were selected from a combinatorial library by phage display resulting in the identification of three unique binders with affinities (KD) for CD16a in the range of 100 nM–3 µM. The affibody exhibiting the highest affinity demonstrated insensitivity towards the CD16a allotype (158F/V) and did not interfere with IgG (Fc) binding to CD16a. For the construction of hBCMA x CD16 dual engagers, different CD16a binding arms, including bi-paratopic affibody combinations, were genetically fused to a high-affinity hBCMA-specific affibody. Such 15–23 kDa dual engager constructs showed simultaneous hBCMA and CD16a binding ability and could efficiently activate resting primary NK cells and trigger specific lysis of a panel of hBCMA-positive multiple myeloma cell lines. Hence, we report a novel class of uniquely small NK cell engagers with specific binding properties and potent functional profiles.
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| 8. |
- Wang, Hao, 1975, et al.
(författare)
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Genome-scale metabolic network reconstruction of model animals as a platform for translational research
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:30
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.
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| 9. |
- Ambikan, Anoop T., et al.
(författare)
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Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
- 2022
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Ingår i: Cell systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 13:8, s. 665-681
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Tidskriftsartikel (refereegranskat)abstract
- The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolo-mics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a sub-stantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and person-alized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as a-ketoglutarate, succi-nate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19.
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| 10. |
- Bergman, Jan, et al.
(författare)
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Oxidative Ring Expansion of Spirocyclic Oxindole Derivatives
- 2014
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 79:19, s. 9065-9073
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation of the spirocyclic oxindole derivative, isamic acid 1, led to decarboxylation and ring expansion to quinazolino[4,5-b]quinazoline-6,8-dione 7 rather than, as previously believed, its isomer 6. The structure of 7 was confirmed by X-ray crystallography. Condensation of isatin (indole-2,3-dione) and 2-aminobenzamide led to the spirocyclic molecule, spiro[3H-indole-3,2'(1H)quinazoline]-2,4'(1H,3H)dione 8, which was also identified as an intermediate in the oxidation of isamic acid. Mild hydrolysis of 7 gave the 10-membered molecule 22. Isamic acid could easily be converted to N-nitrosoisamic acid, which when heated in ethanol underwent a ring expansion to a hydroximino derivative, 38, of compound 6. The structure of 38 was confirmed by X-ray crystallography.
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