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1.
  • Sgaramella, Nicola, et al. (författare)
  • Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1
  • 2015
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:2, s. 321-326
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged <= 40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.
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2.
  • Axmon, A, et al. (författare)
  • Psychiatric diagnoses in older people with intellectual disability in comparison with the general population a register study
  • 2018
  • Ingår i: Epidemiology and Psychiatric Sciences. - 2045-7960. ; 27:5, s. 479-491
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To describe the occurrence of psychiatric diagnoses in a specialist care setting in older people with intellectual disability (ID) in relation to those found in the same age group in the general population.METHOD: A cohort of people with ID (n = 7936), aged 55 years or more in 2012, was identified, as was an age and sex-matched cohort from the general population (n = 7936). Information regarding psychiatric diagnoses during 2002-2012 was collected from the National Patient Register, which contains records from all inpatient care episodes and outpatient specialist visits in Sweden. The mean age at the start of data collection (i.e. January 1st, 2002) was 53 years (range 44-85 years).RESULTS: Seventeen per cent (n = 1382) of the people in the ID cohort had at least one psychiatric diagnosis recorded during the study period. The corresponding number in the general population cohort was 10% (n = 817), which translates to an odds ratio (OR) of 1.84. The diagnoses recorded for the largest number of people in the ID cohort were 'other' (i.e. not included in any of the diagnostic groups) psychiatric diagnoses (10% of the cohort had at least one such diagnosis recorded) and affective disorders (7%). In the general population cohort, the most common diagnoses were affective disorders (4%) and alcohol/substance-abuse-related disorders (4%). An increased odds of having at least one diagnosis was found for all investigated diagnoses except for alcohol/substance-abuse-related disorders (OR = 0.56). The highest odds for the ID cohort was found for diagnosis of psychotic disorder (OR = 10.4) followed by attention deficit/hyperactive disorder (OR = 3.81), dementia (OR = 2.71), personality disorder (OR = 2.67), affective disorder (OR = 1.74) and anxiety disorder (OR = 1.36). People with ID also had an increased odds of psychiatric diagnoses not included in any of these groups (OR = 8.02). The percentage of people with ID who had at least one diagnosis recorded during the study period decreased from more than 30% among those aged 55-59 years in 2012 (i.e. born 1953-1957) to approximately 20% among those aged 75+ years in 2012 (i.e. born in or before 1937).CONCLUSIONS: Older people with ID seem to be more likely to have psychiatric diagnoses in inpatient or outpatient specialist care than their peers in the general population. If this is an effect of different disorder prevalence, diagnostic difficulties or differences in health care availability remains unknown. More research is needed to understand the diagnostic and treatment challenges of psychiatric disorders in this vulnerable group.
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3.
  • Axmon, A, et al. (författare)
  • Psychiatric diagnoses in relation to severity of intellectual disability and challenging behaviors : a register study among older people
  • 2018
  • Ingår i: Aging and Mental Health. - : Informa UK Limited. - 1364-6915 .- 1360-7863. ; 22:10, s. 1344-1350
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate the possible association between severity of intellectual disability (ID) and presence of challenging behavior, respectively, on diagnoses of psychiatric disorders among older people with ID.METHODS: People with a diagnosis of ID in inpatient or specialist outpatient care in 2002-2012 were identified (n = 2147; 611 with mild ID, 285 with moderate ID, 255 with severe or profound ID, and 996 with other/unspecified ID). Moreover, using impairment of behavior as a proxy for challenging behavior, 627 people with, and 1514 without such behavior were identified.RESULTS: Severe/profound ID was associated with lower odds of diagnoses of psychotic, affective, and anxiety disorders than was mild/moderate ID. People with moderate ID had higher odds than those with mild ID of having diagnoses of affective disorders. Diagnoses of psychotic, affective, and anxiety disorders, and dementia were more common among people with challenging behavior than among those without.CONCLUSIONS: People with severe/profound ID had lower odds of receiving psychiatric diagnoses than those with mild and moderate ID. Whether this is a result of differences in prevalence of disorders or diagnostic difficulties is unknown. Further, challenging behaviors were associated with diagnoses of psychiatric disorders. However, the nature of this association remains unclear.
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4.
  • Burrell, Jamie, et al. (författare)
  • Using Curvature Power to Map the Domain of Inverse Micellar Cubic Phases : The Case of Aliphatic Aldehydes in 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine
  • 2017
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 33:44, s. 12804-12813
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxylipins, or fatty aldehydes, are a class of molecules produced from membrane lipids as a result of oxidative stress or enzyme-mediated peroxidation. Here we report the effects of two biologically important fatty aldehydes, trans,trans-2,4-decanedienal (DD) and cis-11-hexadecenal (HD), on the phase behavior of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in water. We compare the phase behavior of DD/DOPE and HD/DOPE mixtures to the phase behavior of oleic acid/DOPE mixtures and show that DD, HD, and oleic acid have similar effects on the phase diagrams of DOPE. Notably, both DD and HD, like oleic acid, induce the formation of Fd3m inverse micellar cubic phases in DOPE/water mixtures. This is the first time that Fd3m phases in fatty aldehyde-containing mixtures have been reported. We assess the effects of DD, HD, and oleic acid on DOPE in terms of lipid spontaneous curvatures and propose a method to predict the formation of Fd3m phases from the curvature power of amphiphiles. This methodology predicts that Fd3m phases will become stable if the spontaneous curvature of a lipid mixture is -0.48 ± 0.05 nm-1 or less.
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5.
  • Dalen, Love, et al. (författare)
  • Identifying Bird Remains Using Ancient DNA Barcoding
  • 2017
  • Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Bird remains that are difficult to identify taxonomically using morphological methods, are common in the palaeontological record. Other types of challenging avian material include artefacts and food items from endangered taxa, as well as remains from aircraft strikes. We here present a DNA-based method that enables taxonomic identification of bird remains, even from material where the DNA is heavily degraded. The method is based on the amplification and sequencing of two short variable parts of the 16S region in the mitochondrial genome. To demonstrate the applicability of this approach, we evaluated the method on a set of Holocene and Late Pleistocene postcranial bird bones from several palaeontological and archaeological sites in Europe with good success.
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6.
  • Lenton, S, et al. (författare)
  • Dynamic footprint of sequestration in the molecular fluctuations of osteopontin.
  • 2015
  • Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5662 .- 1742-5689. ; 12:110
  • Tidskriftsartikel (refereegranskat)abstract
    • The sequestration of calcium phosphate by unfolded proteins is fundamental to the stabilization of biofluids supersaturated with respect to hydroxyapatite, such as milk, blood or urine. The unfolded state of osteopontin (OPN) is thought to be a prerequisite for this activity, which leads to the formation of core-shell calcium phosphate nanoclusters. We report on the structures and dynamics of a native OPN peptide from bovine milk, studied by neutron spectroscopy and small-angle X-ray and neutron scattering. The effects of sequestration are quantified on the nanosecond- ångström resolution by elastic incoherent neutron scattering. The molecular fluctuations of the free phosphopeptide are in agreement with a highly flexible protein. An increased resilience to diffusive motions of OPN is corroborated by molecular fluctuations similar to those observed for globular proteins, yet retaining conformational flexibilities. The results bring insight into the modulation of the activity of OPN and phosphopeptides with a role in the control of biomineralization. The quantification of such effects provides an important handle for the future design of new peptides based on the dynamics-activity relationship.
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7.
  • Nylander, Jan, et al. (författare)
  • Elvägars utveckling– Från demonstratorer till storskaligutbyggnad
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Den övergripande utvecklingen mot el som energikälla för transporter sker nu snabbt. Förtyngre transporter på väg samlas arbetet kring elvägar, d.v.s. att befintliga vägar förses mednågon teknik där fordon, utefter hela eller delar av vägarna, kan tillföras elenergi under drift.Drivkraften för tyngre kommersiella transportfordon är i huvudsak ekonomisk, relaterat tilltransportköpares kostnader och intäkter samt risker och möjligheter relaterat till bl.a.transporter, transportsystem, arbetsmiljö, tillgång till marknader och påverkan avvarumärke. Ur ett hållbarhetsperspektiv är det helt centralt att övergången till el sker i tid,med bibehållen flexibilitet för framtida teknik och system samt med så lågatransaktionskostnader som möjligt. Till detta kommer en politisk ambition som påverkarmyndigheter, skatter, avgifter och regelverk med en katalyserande och systemförändrandeansats. Det är dock viktigt att notera att den offentliga ambitionen aldrig kommer attresultera i leverans av en lösning om inte transportköparna finner det motiverat att nyttjaelvägar.Utvecklingen mot eldrivna transportsystem är tydlig. Däremot är det fortfarande osäkert hurenergin tillförs eller transporteras i fordonet. Det finns inte EN lösning på detta. Olikatillämpning, teknikutveckling och parters förmåga att ta fungerande lösningar till marknadoch nytta kommer steg för steg att styra utvecklingen. Vi kommer under många år att ha olikasamverkande lösningar, beroende på utveckling, kommersiell mognadsgrad, tillämpning ochbehov. Teknik och affärsekosystem kommer på samma sätt att variera. Varor och tjänstermed kort livslängd ska i dessa modeller kombineras med lösningar med mycket långlivslängd. Utvecklingen ska på ett sätt som gör att finansieringen säkras, och på ett sätt somgör att en komplex samling behov från olika intressenter tillgodoses samtidigt som finansiellaincitament och risker balanseras långsiktigt. Så måste även balansen hållas mellan olikaparters mål och medel, så att forskning och utveckling balanseras med utbyggnad och nytta ikundledet. Arbetet inom FFI-projektet ”Forsknings- och innovationsplattform för elvägar”visar att om sträckan mellan Gävle och Borlänge (120 km) skulle elektrifieras skulleinvesteringen betala sina egna kostnader om den trafikerades av en volym om 190elektrifierade lastbilar, givet samma kostnader för infrastruktur som det pågåendedemonstrationsprojektet visat. Mellan Sandviken och Gävle hamn (30 km) bär det sig med50 elektrifierade lastbilar. Möjligheterna är tydliga, finansieringen möjlig, nyttan sannolik, regelverk och förordningar hanterbara, nu gäller det att hålla igång samarbete och tryck föratt tillsammans få detta på plats, nationellt och internationellt.Ur ett samlat hållbarhetsperspektiv är elektrifiering centralt. Det gäller ekonomisk ochmiljörelaterad hållbarhet men även nationalekonomisk där en nationell komparativ fördel ärvår förmåga att driva på och implementera förändringar i multidisciplinära komplexasamhällssystem. Hållbarhetsfrågan har i detta sammanhang även att göra med vår förmågaatt implementera, bygga ut och nyttja klimatsmart väginfrastruktur. Det kombinerar teknik,finansiering, flexibilitet och hänsyn med behov av konkretisering, beslut, utbyggnad ochimplementering; d.v.s. ytterst om ledarskap i multidisciplinära innovationssystem, någotsom är väldigt svårt men där Sverige genom åren visat sig vara bland de bästa.Det är ett mycket viktigt ansvar för politik och myndigheter att sköta denna balans på ett brasätt. Balansen kräver dialog och samarbete, utefter hela förädlingskedjan, från forskning tillkommersiellt nyttjande. De kommande åren är en spännande utmaning för att lagom snabbt,säkert och till rimlig kostnad balansera offentliga och privata roller så attkonkurrensutsättning, upphandlingsbarhet, innovation och utveckling kombineras medansvar, säkerhet och hållbarhet. En central del i utvecklingen är att det affärsekosystem somomger elvägar identifieras, definieras, utvecklas och i viss mån implementeras. Dettakommer även att variera internationellt, bara jämfört med Tyskland finns olika syn där vissadelar är gemensamma och andra alltid kommer att variera. Denna rapport har ambitionen attbidra med ett första steg för en principiell plattform för fortsatt strategiarbete.Denna rapport bör läsas tillsammans med huvudrapporten från förstudien avaffärsekosystem för elvägar (Håkan Sundelin et.al). Denna rapport har ambitionen att bidratill den första strategiska plattform som Trafikverket arbetar med kring utveckling,uppbyggnad, utrullning och nyttjande av elvägar som pågår.Just dialog, diskussion, överväganden och förankring kombinerat med pådrivning leder tillatt denna rapport bara är ett första steg och att en dialog nu tar vid, där alla utefterförädlingskedjan engageras, bidrar och samlas för att elvägar ska komma till nytta isamhället. Rapporten har inget externt syfte, målgruppen är de redan insatta, varförreferenser, direkta eller indirekta, samt annat underlag utelämnats utom där det har direktrelevans i syfte att hålla rapporten kort, effektiv och fokuserad.
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8.
  • Prost, Stefan, et al. (författare)
  • Comparative analyses identify genomic features potentially involved in the evolution of birds-of-paradise
  • 2019
  • Ingår i: GigaScience. - : OXFORD UNIV PRESS. - 2047-217X. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The diverse array of phenotypes and courtship displays exhibited by birds-of-paradise have long fascinated scientists and nonscientists alike. Remarkably, almost nothing is known about the genomics of this iconic radiation. There are 41 species in 16 genera currently recognized within the birds-of-paradise family (Paradisaeidae), most of which are endemic to the island of New Guinea. In this study, we sequenced genomes of representatives from all five major clades within this family to characterize genomic changes that may have played a role in the evolution of the group's extensive phenotypic diversity. We found genes important for coloration, morphology, and feather and eye development to be under positive selection. In birds-of-paradise with complex lekking systems and strong sexual dimorphism, the core birds-of-paradise, we found Gene Ontology categories for "startle response" and "olfactory receptor activity" to be enriched among the gene families expanding significantly faster compared to the other birds in our study. Furthermore, we found novel families of retrovirus-like retrotransposons active in all three de novo genomes since the early diversification of the birds-of-paradise group, which might have played a role in the evolution of this fascinating group of birds.
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9.
  • Wan, Feng, et al. (författare)
  • Lipid Shell-Enveloped Polymeric Nanoparticles with High Integrity of Lipid Shells Improve Mucus Penetration and Interaction with Cystic Fibrosis-Related Bacterial Biofilms
  • 2018
  • Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 10:13, s. 10678-10687
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticle (NP) mediated drug delivery into viscous biomatrices, e.g., mucus and bacterial biofilms, is challenging. Lipid shell-enveloped polymeric NPs (Lipid@NPs), composed of a polymeric NP core coated with a lipid shell, represent a promising alternative to the current delivery systems. Here, we describe the facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in an effective mucus penetration and interaction with cystic fibrosis-related bacterial biofilms. Lipid shell-enveloped polystyrene NPs with high integrity of lipid shells (cLipid@PSNPs) were prepared by using an electrostatically mediated layer-by-layer approach, where the model polystyrene NPs (PSNPs) were first modified with positively charged poly-l-lysine (PLL) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), followed by subsequent fusion with zwitterionic, PEGylated small unilamellar vesicles (SUVs). The interaction of the PSNPs with SUVs was significantly enhanced by modifying the PSNPs with PLL and DOTAP, which eventually resulted in the formation of cLipid@PSNPs, i.e., Lipid@PLL-PSNPs and Lipid@DOTAP-PSNPs. Improved mucus-penetrating property of cLipid@PSNPs was demonstrated by quartz crystal microbalance with dissipation monitoring measurements. Furthermore, fluorescence resonance energy transfer measurements showed that the interaction of the cLipid@PSNPs with bacterial biofilms was significantly promoted. In conclusion, we prepared cLipid@PSNPs via an electrostatically mediated layer-by-layer approach. Our results suggest that the integrity of the lipid envelopes is crucial for enabling the diffusion of Lipid@PSNPs into the mucus layer and promoting the interaction of Lipid@PSNPs with a bacterial biofilm.
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10.
  • Wan, Feng, et al. (författare)
  • Qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant by using quartz crystal microbalance with dissipation monitoring
  • 2019
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 545, s. 162-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the interaction between inhaled nanoparticles and pulmonary surfactant is a prerequisite for predicting the fate of inhaled nanoparticles. Here, we introduce a quartz crystal microbalance with dissipation monitoring (QCM-D)-based methodology to reveal the extent and nature of the biophysical interactions of polymer- and lipid-based nanoparticles with pulmonary surfactant. By fitting the QCM-D data to the Langmuir adsorption equation, we determined the kinetics and equilibrium parameters [i.e., maximal adsorption (Δm max ), equilibrium constant (K a ), adsorption rate constant (k a ) and desorption rate constant (k d )] of polymeric nanoparticles adsorption onto the pulmonary surfactant (e.g., an artificial lipid mixture and an extract of porcine lung surfactant). Furthermore, our results revealed that the nature of the interactions between lipid-based nanoparticles (e.g., liposomes) and pulmonary surfactant was governed by the liposomal composition, i.e., incorporation of cholesterol and PEGylated phospholipid (DSPE-PEG 2000 ) into DOPC-based liposomes led to the adsorption of intact liposomes onto the pulmonary surfactant layer and the mass exchange between the liposomes and pulmonary surfactant layer, respectively. In conclusion, we demonstrate the applicability of the QCM-D technique for qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant, which is vital for rational design and optimization of inhalable nanomedicines.
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