19 research outputs found
Entering the Mystery : Helsinki Noir, a Fictional Detective Story Created in a Museum Space
Peer reviewe
Exploring the Interrelations Between Literature and Museums
Review of: Anastasio, Matteo and Jan Rhein (eds.): Transitzonen zwischen Literatur und Museum. Berlin/Boston: De Gruyter, 2021.Non peer reviewe
FinnGen provides genetic insights from a well-phenotyped isolated population
Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% †minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 Ă 10â11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.publishedVersionPeer reviewe
Coherent anti-Stokes Raman scattering (CARS) microscopy driving the future of loaded mesoporous silica imaging
This study reports the use of variants of coherent anti-Stokes Raman scattering (CARS) microscopy as a novel method for improved physicochemical characterization of drug-loaded silica particles. Ordered mesoporous silica is a biomaterial that can be loaded to carry a number of biochemicals, including poorly water-soluble drugs, by allowing the incorporation of drug into nanometer-sized pores. In this work, the loading of two poorly water-soluble model drugs, itraconazole and griseofulvin, in MCM-41 silica microparticles is characterized qualitatively, using the novel approach of CARS microscopy, which has advantages over other analytical approaches used to date and is non-destructive, rapid, label free, confocal and has chemical and physical specificity. The study investigated the effect of two solvent-based loading methods, namely immersion and rotary evaporation, and microparticle size on the three-dimensional (3-D) distribution of the two loaded drugs. Additionally, hyperspectral CARS microscopy was used to confirm the amorphous nature of the loaded drugs. Z-stacked CARS microscopy suggested that the drug, but not the loading method or particle size range, affected 3-D drug distribution. Hyperspectral CARS confirmed that the drug loaded in the MCM-41 silica microparticles was in an amorphous form. The results show that CARS microscopy and hyperspectral CARS microscopy can be used to provide further insights into the structural nature of loaded mesoporous silica microparticles as biomaterials
Confinement Effects on Drugs in Thermally Hydrocarbonized Porous Silicon
Thermally hydrocarbonized porous
silicon (THCPSi) microparticles
were loaded with indomethacin (IMC) and griseofulvin (GSV) using three
different payloads between 6.2â19.5 and 6.2â11.4 wt
%, respectively. The drug loading parameters were selected to avoid
crystallization of the drug molecules on the external surface of the
particles that would block the pore entrances. The successfulness
of the loadings was verified with TG, DSC, and XRPD measurements.
The effects of the confinement of IMC and GSV into the small mesopores
of THCPSi were analyzed with helium pycnometry, FTIR, and NMR spectroscopy.
The results showed the density of the THCPSi loaded drugs to be ca.
10% lower than the bulk crystalline forms, while a melt quenched amorphous
drugs showed a density reduction of 3â7.5%. DSC and FTIR results
confirmed that the drugs reside in an amorphous form within the THCPSi
pores. Similar results were obtained with NMR, which also indicated
that IMC may reside as both amorphous clusters and individual molecules
within the pores. The <sup>1</sup>H transverse relaxation times (<i>T</i><sub>2</sub>) of amorphous and THCPSi loaded drugs showed
IMC relaxation times of 0.28 ms for both the cases, whereas for GSV
the values were 0.32 and 0.39 ms, respectively, indicating similar
limited mobility in both cases. The results indicated that strong
drugâcarrier interactions were not necessary for stabilizing
the amorphous state of the adsorbed drug. Dissolution tests using
biorelevant media, fasted state simulated intestinal fluid (FaSSIF)
and simulated gastric fluid (SGF), showed that THCPSi-loaded IMC and
GSV were rapidly released in FaSSIF with comparable rates to the amorphous
forms, whereas in SGF the THCPSi reduced the pH dependency in the
dissolution of IMC
FinnGen provides genetic insights from a well-phenotyped isolated population
Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% †minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 Ă 10â11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.Peer reviewe