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| 3. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 4. |
- Curtis, Bruce A., et al.
(författare)
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Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7427, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.
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| 5. |
- Ibis, Fatma, et al.
(författare)
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Nucleation kinetics of calcium oxalate monohydrate as a function of pH, magnesium, and osteopontin concentration quantified with droplet microfluidics
- 2021
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Ingår i: Biomicrofluidics. - : AIP Publishing. - 1932-1058. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- A droplet-based microfluidic platform is presented to study the nucleation kinetics of calcium oxalate monohydrate (COM), the most common constituent of kidney stones, while carefully monitoring the pseudo-polymorphic transitions. The precipitation kinetics of COM is studied as a function of supersaturation and pH as well as in the presence of inhibitors of stone formation, magnesium ions (Mg2+), and osteopontin (OPN). We rationalize the trends observed in the measured nucleation rates leveraging a solution chemistry model validated using isothermal solubility measurements. In equimolar calcium and oxalate ion concentrations with different buffer solutions, dramatically slower kinetics is observed at pH 6.0 compared to pHs 3.6 and 8.6. The addition of both Mg2+ and OPN to the solution slows down kinetics appreciably. Interestingly, complete nucleation inhibition is observed at significantly lower OPN, namely, 3.2 x 10(-8) M, than Mg2+ concentrations, 0.875 x 10(-4) M. The observed inhibition effect of OPN emphasizes the often-overlooked role of macromolecules on COM nucleation due to their low concentration presence in urine. Moreover, analysis of growth rates calculated from observed lag times suggests that inhibition in the presence of Mg2+ cannot be explained solely on altered supersaturation. The presented study highlights the potential of microfluidics in overcoming a major challenge in nephrolithiasis research, the overwhelming physiochemical complexity of urine.
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| 6. |
- Ibis, Fatma, et al.
(författare)
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Role of Hyaluronic Acid on the Nucleation Kinetics of Calcium Oxalate Hydrates in Artificial Urine Quantified with Droplet Microfluidics
- 2022
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 22:6, s. 3834-3844
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Tidskriftsartikel (refereegranskat)abstract
- The increasing prevalence of urolithiasis in industrialized societies triggered considerable interest in how various species found in urine regulate the nucleation and growth of common kidney stone constituents such as calcium oxalate (CaOx). Yet, the role macromolecules play in kidney stone formation is often overlooked due to their low concentration in urine. In this study, we investigate the nucleation kinetics of CaOx in artificial urine with droplet-based microfluidic induction time measurements at varying concentrations of oxalate and hyaluronic acid (HA), a polysaccharide commonly found in urine. The formation of two pseudo-polymorphic forms of calcium oxalate crystals, calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD), are carefully monitored using polarized light microscopy in induction time experiments. COM and COD nucleated concomitantly in artificial urine yet with distinct kinetics. Our results indicate that higher oxalate concentrations favor the formation of COD, the metastable form, over COM, the most stable form. Moreover, COD is also the fastest nucleating form in droplets under studied conditions. Furthermore, increasing the concentration of HA at fixed calcium and oxalate concentrations favored the nucleation of COM. We observed that in droplets where COM nucleated first, COD was not formed within the experimental time scale. However, in the droplets where COD appeared first, COM crystals were also observed later. We hope our findings shed light on the role macromolecules such as HA plays in dictating the pseudo-polymorphic form of CaOx and guide next generation treatments.
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| 7. |
- Korede, Vikram, et al.
(författare)
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Design and Validation of a Droplet-based Microfluidic System To Study Non-Photochemical Laser-Induced Nucleation of Potassium Chloride Solutions
- 2023
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 23:8, s. 6067-6080
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Tidskriftsartikel (refereegranskat)abstract
- Non-photochemicallaser-induced nucleation (NPLIN) hasemergedas a promising primary nucleation control technique offering spatiotemporalcontrol over crystallization with potential for polymorph control.So far, NPLIN was mostly investigated in milliliter vials, throughlaborious manual counting of the crystallized vials by visual inspection.Microfluidics represents an alternative to acquiring automated andstatistically reliable data. Thus we designed a droplet-based microfluidicplatform capable of identifying the droplets with crystals emergingupon Nd:YAG laser irradiation using the deep learning method. In ourexperiments, we used supersaturated solutions of KCl in water, andthe effect of laser intensity, wavelength (1064, 532, and 355 nm),solution supersaturation (S), solution filtration,and intentional doping with nanoparticles on the nucleation probabilityis quantified and compared to control cooling crystallization experiments.Ability of dielectric polarization and the nanoparticle heating mechanismsproposed for NPLIN to explain the acquired results is tested. Solutionswith lower supersaturation (S = 1.05) exhibit significantlyhigher NPLIN probabilities than those in the control experiments forall laser wavelengths above a threshold intensity (50 MW/cm(2)). At higher supersaturation studied (S = 1.10),irradiation was already effective at lower laser intensities (10 MW/cm(2)). No significant wavelength effect was observed besides irradiationwith 355 nm light at higher laser intensities (& GE;50 MW/cm(2)). Solution filtration and intentional doping experimentsshowed that nanoimpurities might play a significant role in explainingNPLIN phenomena. Thearticle describes a droplet-based microfluidic setupto study NPLIN with the droplets containing crystals identified usingthe deep-learning method. Experimental parameters such as solutionsupersaturation, laser wavelength, laser intensity, solution filtration,and intentional doping of nanoparticles are studied using supersaturatedaqueous KCl solutions to quantify its influence on nucleation kineticsand draw parallels to the proposed underlying NPLIN mechanisms inthe literature.
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| 8. |
- Korede, Vikram, et al.
(författare)
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Effect of Laser-Exposed Volume and Irradiation Position on Nonphotochemical Laser-Induced Nucleation of Potassium Chloride Solutions
- 2023
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 23:11, s. 8163-8172
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we study the influences of the laser-exposed volume and the irradiation position on the nonphotochemical laser-induced nucleation (NPLIN) of supersaturated potassium chloride solutions in water. The effect of the exposed volume on the NPLIN probability was studied by exposing distinct milliliter-scale volumes of aqueous potassium chloride solutions stored in vials at two different supersaturations (1.034 and 1.050) and laser intensities (10 and 23 MW/cm2). Higher NPLIN probabilities were observed with increasing laser-exposed volume as well as with increasing supersaturation and laser intensity. The measured NPLIN probabilities at different exposed volumes are questioned in the context of the dielectric polarization mechanism and classical nucleation theory. No significant change in the NPLIN probability was observed when samples were irradiated at the bottom, top, or middle of the vial. However, a significant increase in the nucleation probability was observed upon irradiation through the solution meniscus. We discuss these results in terms of mechanisms proposed for NPLIN.
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