| 1. |
- Holmgren, Gustav, 1983-, et al.
(author)
-
Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells
- 2015
-
In: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 328, s. 102-111
-
Journal article (peer-reviewed)abstract
- Doxorubicin is a chemotherapeutic agent indicated for the treatment of a variety of cancer types, including leukaemia, lymphomas, and many solid tumours. The use of doxorubicin is, however, associated with severe cardiotoxicity, often resulting in early discontinuation of the treatment. Importantly, the toxic symptoms can occur several years after the termination of the doxorubicin administration. In this study, the toxic effects of doxorubicin exposure have been investigated in cardiomyocytes derived from human embryonic stem cells (hESC). The cells were exposed to different concentrations of doxorubicin for up to 2 days, followed by a 12 day recovery period. Notably, the cell morphology was altered during drug treatment and the cells showed a reduced contractile ability, most prominent at the highest concentration of doxorubicin at the later time points. A general cytotoxic response measured as Lactate dehydrogenase leakage was observed after 2 days' exposure compared to the vehicle control, but this response was absent during the recovery period. A similar dose-dependant pattern was observed for the release of cardiac specific troponin T (cTnT) after 1 day and 2 days of treatment with doxorubicin. Global transcriptional profiles in the cells revealed clusters of genes that were differentially expressed during doxorubicin exposure, a pattern that in some cases was sustained even throughout the recovery period, suggesting that these genes could be used as sensitive biomarkers for doxorubicin-induced toxicity in human cardiomyocytes. The results from this study show that cTnT release can be used as a measurement of acute cardiotoxicity due to doxorubicin. However, for the late onset of doxorubicin-induced cardiomyopathy, cTnT release might not be the most optimal biomarker. As an alternative, some of the genes that we identified as differentially expressed after doxorubicin exposure could serve as more relevant biomarkers, and may also help to explain the cellular mechanisms behind the late onset apoptosis associated with doxorubicin-induced cardiomyopathy.
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| 2. |
- Kettunen, Petronella, et al.
(author)
-
Genetic Variants of GSK3B are Associated with Biomarkers for Alzheimer's Disease and Cognitive Function
- 2015
-
In: Journal of Alzheimers Disease. - 1387-2877. ; 44:4, s. 1313-1322
-
Journal article (peer-reviewed)abstract
- Background: Glycogen synthase kinase 3 beta (GSK3B) is the major kinase phosphorylating tau protein. Hyperphosphorylated tau is one of the hallmarks of Alzheimer's disease (AD). Despite extensive research, the role of GSK3B in AD pathogenesis is not fully understood.Objective: To evaluate possible associations between gene variants of GSK3B and risk of AD. Methods: Twelve GSK3B tag single-nucleotide polymorphisms (SNPs), together with the previously AD-associated rs334558, were analyzed in 583 AD patients and 673 controls. Analyses on single marker and haplotype levels were done to relate to risk of AD, Mini-Mental State Examination (MMSE) scores, and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau (P-tau(181)), and amyloid-beta (A beta(42)).Results: After correction for multiple testing, we found a number of associations of gene variants with CSF biomarker levels and cognitive function in the AD patients. Firstly, rs334558 was associated with elevated T-tau levels (p(c) = 0.04). Next, rs1154597 showed association with reducedA beta(42) levels (pc = 0.007). Lastly, rs3107669was associated with lower MMSE scores (p(c) = 0.03). In addition, one more SNP was nominally significantly associated with reduced A beta(42) levels and another was associated with reduced MMSE.Conclusion: We found GSK3B gene variants associated with cognitive function and CSF biomarkers T-tau and A beta(42). To our knowledge, this is the first time GSK3B has been associated with cognitive function or CSF biomarkers reflecting neuronal degeneration (T-tau) and brain amyloid load (A beta(42)). The regulation of GSK3B needs to be investigated further, to fully understand how these GSK3B gene variants are involved in AD pathogenesis.
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| 3. |
- Asplund, Annika, 1979-, et al.
(author)
-
One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells
- 2016
-
In: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:1, s. 90-104
-
Journal article (peer-reviewed)abstract
- Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using one standardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.
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| 4. |
- Bach, Andreas, et al.
(author)
-
HAMNEN SOM ENERGINOD : Ett koncept för hamnens roll i omställningen mot ett hållbart transportsystem
- 2022
-
Reports (other academic/artistic)abstract
- Transportsystemet står inför en enorm utmaning då trycket på genomförandet av hållbara operationer aldrig varit större. Enligt IEA står transportsektorn för 16% av det totala koldioxidutsläppet i världen som med nödvändighet måste minska för att vi ska kunna lämna efter oss en planet med resurser för framtida generationer. Utmaningen kräver att alla delar av transportsystemet gör sitt bidrag, oavsett om det handlar om transportoperatörer, transportnoder, myndigheter på såväl lokal, regional som global nivå och tvärs samtliga transportslag. Det slutar dock inte där, det är lika viktigt att de som konstruerar olika typer av lastbärare och fordon för både gods- och persontransporter också beaktar den energi som förväntas vara tillgänglig i rätt kvantitet och till rätt pris. Energiproducenter behöver också tillgodose att efterfrågade energibärare produceras och finns att tillgå vid rätt plats och i tillräcklig kvantitet då den behövs. Detta är i linje med de behov av insatser som Sveriges regering lyfter inom transporteffektivitet, hållbara förnybara drivmedel samt energieffektiva fordon och fartyg, för att reducera Sveriges territoriella CO2 utsläpp i linje med de globala målen. En viktig del av transportsystemet är hamnar som har fönster mot flera olika transportslag och utgör multimodala noder som förväntas ombesörja en så sömlös övergång mellan olika transportslag som möjligt, såsom till/från sjö, järnväg och väg. Svenska hamnar är inget undantag, utan i Sverige med sin längsta europeiska kustremsa behöver Sveriges hamnar också etablera tillräcklig kapabilitet för att hantera såväl inhemska transportbehov som förväntade transporter för import och export på ett hållbart sätt. Hamnar står inför utmaningen att både bedriva sina operationer på ett så hållbart sätt som möjligt genom nyttjande av fossilfri energi, att förse besökare med fossilfria energibärare, och att balansera sitt nyttjande och distribution av hållbar energi med de behov som omgivningen har. Organisationer med lastbilar, tåg, och fartyg som besöker en transportnod, däribland hamnar, förväntar sig att de kan försörjas med viss energi. Transportnoder kan således inte bara betraktas utifrån att vara en effektiv omlastningspunkt, utan behöver också betraktas utifrån den roll som transportnoden har och kan komma att ta i den del av energisystemet som relaterar till transportsystemet. Hamnar som transportnoder behöver således etablera en förmåga som energinod. I föreliggande projekt har trender beaktats för utvecklingen inom olika transportslag, intervjuer genomförts med svenska hamnar samt en enkätundersökning genomförts riktad till en majoritet av Sveriges hamnar. I projektet identifieras att de viktigaste drivkrafterna för hamnarnas hållbarhets- och omställningsarbete är kundkrav, kostnadsbesparingar, hamnens interna målsättning (ofta baserad på ägarnas krav och vision) samt regelverk. Slutsatsen är att Sveriges hamnar har en stark ambition att utveckla sin förmåga som energinod för olika roller. Samtidigt råder en villrådighet om vilka satsningar som skulle ge störst effekter för hamnens verksamhet. Viktigt att notera är också att olika hamnar har olika förutsättningar och roller i transportsystemet, beroende på dess geografiska placering, storlek och typ av gods / passagerare som hanteras. Samtidigt görs stora investeringar i Sveriges hamnsystem, för att proaktivt utveckla en kapabilitet att möta dagens och morgondagens transportbehov, särskilt i ljuset av den omflyttning som sker från vägbundna transporter till järnväg och sjö. Det är vanligt att hamnar etablerar inlandsterminalskapabilitet, d v s skapar förmåga för omlastning mellan tåg och väg där inte någon sjötransport behöver vara inblandad. Många av Sveriges järnvägsoperatörer ser hamnar som strategiska noder i järnvägssystemet. Dessutom det är tydligt från intervjuerna, vilket även styrks av enkätsvar, att respondenterna anser att otillräckliga finansiella medel, höga kostnader och skatt, omogen teknik, infrastruktur, effekt, standardisering, kompetens, och politisk otydlighet är de största utmaningar som påverkar svenska hamnars roll i hållbarhets- och omställningsarbete. Baserat på genomförd trend- och nulägesanalys föreslås en mognadsmodell som rådgivande för hamnens proaktiva utveckling av sin energinodskapacitet. Denna modell tar utgångspunkt i att hamnen etablerar en energistrategi som tar höjd för nödvändiga samarbeten och investeringar som de både blir tvingade till genom regelverk, påverkade av genom beslut och själva har rådighet över. Hamnarna är tydliga med att huvudverksamheten är att utgöra en transportnod, men att de, för att möjliggöra en omställning mot ett hållbart transportsystem, också behöver ge utrymme för andra aktörer, såsom energiproducenter och energidistributörer att bedriva sin verksamhet relaterat till hamnens geografiska område. Således behöver det kluster av aktörer som ingår i hamnen som nod expanderas till att också innefatta producenter och distributörer av energi. Hamnens energistrategi är rådgivande för att hamnen skall kunna etablera en förmåga som säkerställer att de krav som hamnens operationer, hamnens besökare och hamnens roll med sin geografiska placering, möts. Föreslagen mognadsmodell riktar uppmärksamhet just till dessa nivåer av förmåga och skapar grunder för formuleringen av en proaktiv strategi för den enskilda hamnens roll i transportsystemets energiomställning. En viktig grund blir då att simulera framtida energibehov, såsom inom elförsörjnings- och eldistributionsområdet, men även för andra energibärare, varför detta projekt föreslår ett fortsättningsprojekt där förväntade energibehov kan simuleras och bli rådgivande för strategi, samverkan och investering för Sveriges hamnar. En sådan simuleringsmodell bygger på hamnens digitala förmåga att fånga och använda data från operationer för att säkerställa att hamnen bidrar till transporteffektivitet, användning av hållbara förnybara drivmedel samt energieffektiva fordon och fartyg. Samspelet mellan hamnen som energinod och transportbärares kapabilitet att drivas på hållbar energi samt energiproducenters/energidistributörers förmåga att tillhandahålla fossilfri energi, utgör grunden till fossilfria transporter. Fossilfria väg-, järnvägs- och sjötransporter kan således inte etableras utan att ta hänsyn till alla ingående komponenter. I denna nödvändiga transformation har hamnar och andra transportnoder en nyckelroll.
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| 5. |
- Backlund, Sandra
(author)
-
Efficient improvement of energy efficiency in small and medium- sized Swedish firms
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- This is a dissertation about efficient implementation of energy efficiency measures in small and medium-sized Swedish firms. The aim is to investigate the potential for economically efficient implementation of energy efficiency improvement measures in small and medium-sized firms. The thesis contains five papers that analyse different aspects that have been put forth in policy documents and academic debate as methods to improve energy efficiency in non-energy intensive sectors.By reading policy documents, interviewing representatives of small and medium- sized firms and energy auditors as well as analysing data from the Swedish energy audit program, different aspects of energy management practices, energy services and energy audits are considered. The thesis is the product of an interdisciplinary context but economic theory is at the foundation of the analysis and has helped formulate questions and hypotheses that have been tested and explored with the data.The results show that while the potential for improving energy efficiency in the small and medium- sized sector in Sweden is large there are challenges to realizing it in each individual firm. There is potential for improving energy efficiency in the sector and not just for investments in new technology but also for adjusting existing machinery and changing behaviour, but costs for investigating the potential and implementing the measures are large relative to the improvement potential in each company. Energy management practices in this sector are lacking and energy services will only be demanded if reduction in production cost is estimated larger than transaction costs of the service. The Swedish energy audit program has led to the implementation of energy efficiency improvements in the participating firms but compared to other policy instruments it has been a less cost-efficient way to improve energy efficiency in Sweden.
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| 6. |
- Daborg, Jonny, et al.
(author)
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Complement Gene Single Nucleotide Polymorphisms and Biomarker Endophenotypes of Alzheimer's Disease
- 2013
-
In: Journal of Alzheimer's Disease. - 1387-2877. ; 35:1, s. 51-57
-
Journal article (peer-reviewed)abstract
- The complement system has been implicated in both physiological synapse elimination and Alzheimer's disease (AD). Here, we investigated associations between four single nucleotide polymorphisms (SNPs) in complement genes and cerebrospinal fluid (CSF) biomarkers for AD in 452 neurochemically or neuropathologically verified AD cases and 678 cognitively normal controls. None of the SNPs associated with risk of AD but there were potential associations of rs9332739 in the C2 gene and rs4151667 in the complement factor B gene with CSF tau levels (p = 0.023) and Mini-Mental State Examination scores (p = 0.012), both of which may be considered markers of disease intensity/severity.
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| 7. |
- Gustafsson, Karin, 1980, et al.
(author)
-
Tumour-loaded alpha-type 1-polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK-, NKT- and CD8(+) T Cell-attracting Chemokine Profile
- 2011
-
In: Scandinavian Journal of Immunology. - 0300-9475. ; 74:3, s. 318-326
-
Journal article (peer-reviewed)abstract
- Tumour-loaded dendritic cells (DCs) from patients with chronic lymphocytic leukaemia (CLL) matured using an α-type 1-polarized DC cocktail (IL-1β/TNF-α/IFN-α/IFN-γ/poly-I:C;αDC1) were recently shown to induce more functional CD8+ T cells against autologous tumour cells in vitro than DCs matured with the ‘standard’ cocktail (IL-1β/TNF-α/IL-6/PGE2;PGE2DCs). However, the ability of vaccine DCs to induce a type 1-polarized immune response in vivo probably relies on additional features, including their ability to induce a CXCR3-dependent recruitment of NK cells into vaccine-draining lymph nodes. Moreover, their guiding of rare tumour-specific CD8+ T cells to sites of DC–CD4+ T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine profile and the lymphocyte-attracting ability in vitro of monocyte-derived PGE2DCs and αDC1s from patients with CLL. αDC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE2DCs. Functional studies further demonstrated that αDC1s were superior recruiters of both NK and NKT cells. Moreover, αDC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional αDC1s, derived from patients with CLL, produce a desirable NK-, NKT- and CD8+ T cell-attracting chemokine profile which may favour a guided and Th1-deviated priming of CD8+ T cells, supporting the idea that αDC1-based vaccines have a higher immunotherapeutic potential than PGE2DCs.
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| 8. |
- Gustafsson, Karin, et al.
(author)
-
Tumour-loaded alpha-type 1-polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK-, NKT- and CD8(+) T Cell-attracting Chemokine Profile
- 2011
-
In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 74:3, s. 318-326
-
Journal article (peer-reviewed)abstract
- Tumour-loaded dendritic cells (DCs) from patients with chronic lymphocytic leukaemia (CLL) matured using an a-type 1-polarized DC cocktail (IL-1 beta/TNF-alpha/IFN-alpha/IFN-gamma/poly-I:C;alpha DC1) were recently shown to induce more functional CD8(+) T cells against autologous tumour cells in vitro than DCs matured with the 'standard' cocktail (IL-1 beta/TNF-alpha/IL-6/PGE(2);PGE(2)DCs). However, the ability of vaccine DCs to induce a type 1-polarized immune response in vivo probably relies on additional features, including their ability to induce a CXCR3-dependent recruitment of NK cells into vaccine-draining lymph nodes. Moreover, their guiding of rare tumour-specific CD8(+) T cells to sites of DC-CD4(+) T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine profile and the lymphocyte-attracting ability in vitro of monocyte-derived PGE(2)DCs and alpha DC1s from patients with CLL. alpha DC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE(2)DCs. Functional studies further demonstrated that alpha DC1s were superior recruiters of both NK and NKT cells. Moreover, alpha DC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional alpha DC1s, derived from patients with CLL, produce a desirable NK-, NKT- and CD8(+) T cell-attracting chemokine profile which may favour a guided and Th1-deviated priming of CD8(+) T cells, supporting the idea that alpha DC1-based vaccines have a higher immunotherapeutic potential than PGE(2)DCs.
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| 9. |
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| 10. |
- Holmgren, Karin, et al.
(author)
-
The vulnerable continent (PLATINA) : Historical perspectives on Africa´s climate, environment and societies
- 2009
-
In: Meeting global challenges in research cooperation. - Uppsala : Uppsala University. - 9789197574198 ; , s. 585-596
-
Conference paper (peer-reviewed)abstract
- Our research, based on studies of different climate archives from Tanzania, Mozambique and South Africa, contributes information on changes in climate and vegetation over the past 24000 years. This time perspective, reaching beyond the information available from instrumental records is needed for a better understanding of regional global climate dynamics and issues surrounding environmental change, throughout Africa, and is a prerequisite for increasing climate forecasting capabilities for the region. We argue that African people have vast experience from living in a variable climate and research on past interactions between climate and societies demonstrate the significance of lessons learnt for present situations. Our findings, underline the complex interactions between climate/environment and societies that may lead to different developments in time and space. Considering the so called vulnerable continent, extended investigations of how African communities cope with and adapt to climatically driven changes is needed to increase the capability to realise the potential as well as the limitations, of modern African communities to adapt to future climate change.
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| 11. |
- Holmgren, Karin, et al.
(author)
-
Water-level variations in Lake Nhauhache, Mozambique, during the last 2,300 years
- 2012
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In: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 48:2, s. 311-322
-
Journal article (peer-reviewed)abstract
- Stratigraphic variations in diatom composition and phytolith abundance in a sediment core from a small, hydrologically isolated waterbody, Lake Nhauhache, Mozambique, provide evidence of water-level fluctuations over the past 2,300 years. Ten AMS radiocarbon dates on bulk sediment samples show that the lake came into existence about 2,300 years ago and that it has dried out since then, but only for brief time periods. Changes in the diatom assemblage composition indicate that lake level fluctuated in response to shifting humidity conditions. The changes reflect wetter conditions ca. 300 BC-AD 800, more variable conditions between AD 800 and 1150, a distinct dry phase within the time span AD 1150-1700 and a return thereafter to more humid conditions until present. There is general agreement between the Lake Nhauhache record and other records from the Southern Hemisphere summer rainfall region. This suggests that sediments from small interdunal lakes, which are abundant along the coast of southern Africa, provide reliable, regional paleoenvironmental information about an area from which more such data are needed.
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| 12. |
- Holmgren, Sandra, et al.
(author)
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Resolving the taxonomic conundrum in Graphoderus of the east Palearctic with a key to all species (Coleoptera, Dytiscidae).
- 2016
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In: ZooKeys. - 1313-2989 .- 1313-2970. ; :574, s. 113-142
-
Journal article (peer-reviewed)abstract
- The Holarctic diving beetle genus Graphoderus (Dytiscinae, Aciliini) contains relatively few and well-known species but these may still be difficult to identify based on external characters. A taxonomic problem in the eastern Palearctic was discovered that relates to the Palearctic Graphoderus zonatus (Hoppe, 1795) and the Nearctic Graphoderus perplexus Sharp, 1882. Based on qualitative and quantitative characters, especially on male genitalia which have been poorly studied in the past, it is shown that eastern Palearctic specimens identified by previous authors as either of the two species in fact belongs to a third species. The synonymized name Graphoderus elatus Sharp, 1882, is reinstated as a valid species (stat. n.) and a lectotype is designated from the mixed syntype series. The male genitalia of all known Graphoderus species have been examined and an illustrated identification key to the genus is provided. The three species in the complex of focus, Graphoderus elatus, Graphoderus zonatus and Graphoderus perplexus are found to have allopatric distributions; Graphoderus perplexus in the Nearctic region, Graphoderus zonatus in the west Palearctic region and eastwards to the Yenisei-Angara river and Graphoderus elatus east of the Yenisei-Angara river. All previous records of either Graphoderus zonatus or Graphoderus perplexus in the east Palearctic, east of the Yenisei-Angara river turned out to be misidentified Graphoderus elatus. This conclusion also brings with it that dimorphic females, thought only to be present in the single subspecies Graphoderus zonatus verrucifer (CR Sahlberg, 1824), proved to be present also in a second species, Graphoderus elatus. The dimorphic female forms is either with dorsally smooth elytra and pronotum or conspicuously granulated elytra and wrinkly pronotum. As has been shown in Graphoderus zonatus verrucifer there is a correlation between the occurrence of granulate female forms in a population and an increase in the number of adhesive discs on pro- and mesotarsus in males within Graphoderus elatus.
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| 13. |
- Holmgren, Sandra, et al.
(author)
-
Resolving the taxonomic conundrum in Graphoderus of the east Palearctic with a key to all species (Coleoptera, Dytiscidae)
- 2016
-
In: ZooKeys. - : Pensoft Publishers. - 1313-2989 .- 1313-2970. ; :574, s. 113-142
-
Journal article (peer-reviewed)abstract
- The Holarctic diving beetle genus Graphoderus (Dytiscinae, Aciliini) contains relatively few and well-known species but these may still be difficult to identify based on external characters. A taxonomic problem in the eastern Palearctic was discovered that relates to the Palearctic G. zonatus (Hoppe, 1795) and the Nearctic G. perplexus Sharp, 1882. Based on qualitative and quantitative characters, especially on male genitalia which have been poorly studied in the past, it is shown that eastern Palearctic specimens identified by previous authors as either of the two species in fact belongs to a third species. The synonymized name G. elatus Sharp, 1882, is reinstated as a valid species (stat. n.) and a lectotype is designated from the mixed syntype series. The male genitalia of all known Graphoderus species have been examined and an illustrated identification key to the genus is provided. The three species in the complex of focus, G. elatus, G. zonatus and G. perplexus are found to have allopatric distributions; G. perplexus in the Nearctic region, G. zonatus in the west Palearctic region and eastwards to the Yenisei-Angara river and G. elatus east of the Yenisei-Angara river. All previous records of either G. zonatus or G. perplexus in the east Palearctic, east of the Yenisei-Angara river turned out to be misidentified G. elatus. This conclusion also brings with it that dimorphic females, thought only to be present in the single subspecies G. zonatus verrucifer (CR Sahlberg, 1824), proved to be present also in a second species, G. elatus. The dimorphic female forms is either with dorsally smooth elytra and pronotum or conspicuously granulated elytra and wrinkly pronotum. As has been shown in G. z. verrucifer there is a correlation between the occurrence of granulate female forms in a population and an increase in the number of adhesive discs on pro- and mesotarsus in males within G. elatus.
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| 14. |
- Höjer Holmgren, Karin, et al.
(author)
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Part 1 : Tracing Russian VX to its synthetic routes by multivariate statistics of chemical attribution signatures
- 2018
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In: Talanta. - : Elsevier. - 0039-9140 .- 1873-3573. ; 186, s. 586-596
-
Journal article (peer-reviewed)abstract
- Chemical attribution signatures (CAS) associated with different synthetic routes used for the production of Russian VX (VR) were identified. The goal of the study was to retrospectively determine the production method employed for an unknown VR sample. Six different production methods were evaluated, carefully chosen to include established synthetic routes used in the past for large scale production of the agent, routes involving general phosphorus-sulfur chemistry pathways leading to the agent, and routes whose main characteristic is their innate simplicity in execution. Two laboratories worked in parallel and synthesized a total of 37 batches of VR via the six synthetic routes following predefined synthesis protocols. The chemical composition of impurities and byproducts in each route was analyzed by GC/MS-EI and 49 potential CAS were recognized as important markers in distinguishing these routes using Principal Component Analysis (PCA). The 49 potential CAS included expected species based on knowledge of reaction conditions and pathways but also several novel compounds that were fully identified and characterized by a combined analysis that included MS-CI, MS-EI and HR-MS. The CAS profiles of the calibration set were then analyzed using partial least squares discriminant analysis (PLS-DA) and a cross validated model was constructed. The model allowed the correct classification of an external test set without any misclassifications, demonstrating the utility of this methodology for attributing VR samples to a particular production method. This work is part one of a three-part series in this Forensic VSI issue of a Sweden-United States collaborative effort towards the understanding of the CAS of VR in diverse batches and matrices. This part focuses on the CAS in synthesized batches of crude VR and in the following two parts of the series the influence of food matrices on the CAS profiles are investigated.
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| 15. |
- Larsson, Susanna, et al.
(author)
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Proteome of Personalized Tissue-Engineered Veins
- 2024
-
In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 9:13, s. 14805-14817
-
Journal article (peer-reviewed)abstract
- Vascular diseases are the largest cause of death globally and impose a major global burden on healthcare. The gold standard for treating vascular diseases is the transplantation of autologous veins, if applicable. Alternative treatments still suffer from shortcomings, including low patency, lack of growth potential, the need for repeated intervention, and a substantial risk of developing infections. The use of a vascular ECM scaffold reconditioned with the patient's own cells has shown successful results in preclinical and clinical studies. In this study, we have compared the proteomes of personalized tissue-engineered veins of humans and pigs. By applying tandem mass tag (TMT) labeling LC/MS-MS, we have investigated the proteome of decellularized (DC) veins from humans and pigs and reconditioned (RC) DC veins produced through perfusion with the patient's whole blood in STEEN solution, applying the same technology as used in the preclinical studies. The results revealed high similarity between the proteomes of human and pig DC and RC veins, including the ECM texture after decellularization and reconditioning. In addition, functional enrichment analysis showed similarities in signaling pathways and biological processes involved in the immune system response. Furthermore, the classification of proteins involved in immune response activity that were detected in human and pig RC veins revealed proteins that evoke immunogenic responses, which may lead to graft rejection, thrombosis, and inflammation. However, the results from this study imply the initiation of wound healing rather than an immunogenic response, as both systems share the same processes, and no immunogenic response was reported in the preclinical and clinical studies. Finally, our study assessed the application of STEEN solution in tissue engineering and identified proteins that may be useful for the prediction of successful transplantations.
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| 16. |
- Meyer, Antoine, et al.
(author)
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Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis
- 2024
-
In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 59:4, s. 558-568
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Journal article (peer-reviewed)abstract
- Background: Nutri-score is now widely available in food packages in Europe.Aim: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.Results: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p-trend: 0.76).Conclusions: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.
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| 17. |
- Norström, Elin, et al.
(author)
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Coastal paleo-environment and sea-level change at Macassa Bay, southern Mozambique, since c. 6600 cal BP
- 2012
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In: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 260, s. 153-163
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Journal article (peer-reviewed)abstract
- Changes in Holocene coastal paleo-environment and sea-level variations have been recorded in estuary sediments from Macassa Bay, southern Mozambique. Methods include analysis of fossil diatoms, sediment stratigraphy, mineral magnetic properties, stable carbon and nitrogen isotope composition and carbon and nitrogen content. The chronology, based on six AMS 14C dates, suggests a basal age of the sediment core of c 6600 cal BP (calibrated years Before Present). The multi-proxy dataset implies two phases when the site was experiencing marine conditions and tentative sea-level high-stands: 1) between c 6600–6300 cal BP which is contemporary with the last phase of the global transgression and the Holocene climatic optimum, and 2) between c 4700–1000 cal BP, a period when sea level curves from the region suggest occasional minor sea level high-stands. Between these phases (c 6300–4700 cal BP), the environment within the Macassa Bay estuary was less influenced by marine processes, and studied proxies indicate a freshwater phase associated with relatively low sea levels. After c 1000 cal BP, a terrestrial environment prevailed at the site, probably as a result of a combined effect of sea level lowering and high accumulation of organic peat within the estuary.
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| 18. |
- Ramzy, Ihab S, et al.
(author)
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Early effect of surgical revascularisation on left ventricular twist function
- 2015
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In: International Cardiovascular Forum Journal. - : Barcaray Publishing. - 2410-2636 .- 2409-3424. ; 4, s. 16-23
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Journal article (peer-reviewed)abstract
- <p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p><p style="margin: 0cm 0cm 10pt; text-align: justify;"><span style="font-family: 'Times New Roman','serif';"><span style="font-size: medium;">The direct effect of coronary artery bypass graft (CABG) surgery on early recovery of myocardial function, particularly twist and rotation is not well studied. </span></span></p><p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p><p style="margin: 0cm 0cm 10pt; text-align: justify;"><span style="font-family: 'Times New Roman','serif';"><span style="font-size: medium;">Aim: To assess the early response of the 3 myocardial components, circumferential, longitudinal and oblique to CABG in patients with isolated coronary disease.</span></span></p><p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p><p style="margin: 0cm 0cm 10pt; text-align: justify;"><span style="font-family: 'Times New Roman','serif';"><span style="font-size: medium;">Methods: We studied 14 patients, age 64±10 years, before CABG and before hospital discharge using various Doppler echocardiographic techniques including speckle tracking, and compared them with 28 age matched controls.</span></span></p><p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p><p style="margin: 0cm 0cm 10pt; text-align: justify;"><span style="font-family: 'Times New Roman','serif';"><span style="font-size: medium;">Results: Before surgery: Compared to controls, patients had significantly reduced LVEF (p=0.01) but maintained stroke volume (SV) (p=0.5). Diastolic LV function indices were statistically abnormal (p=0.01). LV lateral wall long axis amplitude and myocardial systolic velocities were both reduced (p=0.01) as was septal amplitude of motion (p=0.05). LV peak global longitudinal strain (GLS) was reduced as were systolic and early diastolic global longitudinal strain rates (p=0.01 for all). LV peak basal and apical rotations, twist and torsion were not different. Q-peak basal rotation was shorter than controls (p=0.01).</span></span></p><p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p><p style="margin: 0cm 0cm 10pt; text-align: justify;"><span style="font-family: 'Times New Roman','serif';"><span style="font-size: medium;">After surgery: None of these measurements changed except peak GLS which further reduced (p=0.01). Pre-operatively, SV correlated with global LV function: twist (r= -0.65, p=0.01), and LV torsion (r=-0.66, p=0.01) but LVEF did not correlate with either. Post-operatively, SV correlated with E/A ratio (r=0.66, p=0.01), and the time interval Q- peak basal rotation rate (r=0.8, p=0.002).</span></span></p><p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p><p style="margin: 0cm 0cm 10pt; text-align: justify;"><span style="font-family: 'Times New Roman','serif';"><span style="font-size: medium;">Conclusion: CABG does not result in significant early segmental LV functional improvement along its three myocardial components, but SV becomes dependent on early basal rotation and filling pressures.</span></span></p><p style="margin: 0cm 0cm 10pt; text-align: justify;"> </p>
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| 19. |
- Raúl Sitoe, Sandra, 1979-, et al.
(author)
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Paleo-environment and flooding of the Limpopo River-plain, Mozambique, between c. AD 1200-2000
- 2015
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In: Catena (Cremlingen. Print). - : Elsevier BV. - 0341-8162 .- 1872-6887. ; 126, s. 105-116
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Journal article (peer-reviewed)abstract
- Multi-proxy analysis was performed on a radiocarbon-dated core, collected from a relic oxbow lake in theLimpopo River-plain, Mozambique, with the aim to reconstruct paleo-environment and past flooding of thelower river system over the past c. 800 years. An additional objective was to evaluate and investigate the potentialuse of different proxies as recorders of paleo-flooding events and paleo-environmental variability within thefloodplain. The proxies applied in this study were: mineral magnetic properties, grain-size distribution, organiccarbon content and diatom microfossil assemblages.We found that sediment grain-size and mineral magneticproperties of the minerogenic fraction were the most sensitive proxies in terms of detecting signals from highintensityriver-discharge events. In the 800 year long sequence, variations in sand content, magnetic susceptibilityand saturation isothermal remnant magnetization suggest at least four major flooding events at the siteduring the reconstructed period; in the mid-1200, late-1300, mid-1500 AD and during the last century. Thediatom proxy reflects the development of the site from an open oxbow lake to a mainly terrestrial area. Thediatom assemblage indicates that open lake conditions prevailed at the site between c. AD 1200–1400, withperiodic inundation by marine water, most likely due to late Holocene sea-level changes. From c. AD 1400 andonwards, diatoms were rarely deposited at the site, which indicates drier conditions. This was a result of soilformation and gradual in-filling of the lake, a processwhich possiblywas accentuated by a regionally dry climatesituation. Our study shows that oxbow lakes and the proxies used here have great potential for reconstructingflooding events, a knowledge that is crucial for potential prediction and mitigation of flooding events inMozambique in the future. Although chronological uncertainties limit comparisons to other paleoenvironmentalrecords, it seems that the flooding events recorded at our site occurred both during regionallywet and dry periods. Our data infer however, that flooding was probably more clearly recorded during thelake-stages than during infilled stage, probably as the terrestrial environment was more exposed to erosion.
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| 20. |
- Siwe, Ulf, et al.
(author)
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Sea Traffic Management – Concepts and Components
- 2015
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In: 14th International Conference on Computer and IT Applications in the Maritime Industries.
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Conference paper (peer-reviewed)abstract
- This paper gives an overview of all components making up the Sea Traffic Management (STM) concept. STM builds upon information sharing in the whole maritime transport chain, where informationis shared as early as possible about intentions and reached states. Sea System Wide Information Management will provide an infrastructure for a regulated and federated approach to informationsharing. The functional sub-concepts are described: Strategic Voyage Management, Dynamic Voyage Management, Flow Management and Port Cooperative Decision Making. We will elaborate on how they complement each other and which benefits each of them has in regards to safety, environment and efficiency
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| 21. |
- Zhao, Ying, et al.
(author)
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Residual compromised myocardial contractile reserve after valve replacement for aortic stenosis
- 2012
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In: European Heart Journal Cardiovascular Imaging. - Oxford : Oxford University Press. - 2047-2404 .- 2047-2412. ; 13:4, s. 353-360
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Journal article (peer-reviewed)abstract
- Objective: Despite recovery of left ventricular (LV) function and morphology after aortic valve replacement (AVR) for aortic stenosis (AS), its relationship with exercise capacity remains unknown. Twenty-one AVR patients (age 61 +/- 12 years, 14 male) with normal ejection fraction (EF, 64 +/- 7%) and 21 age- and sex-matched controls (57 +/- 9 years, 10 male, EF 68 +/- 8%) were studied.Methods and results: All subjects performed semi-supine bicycle exercise and speckle tracking echocardiography (STE) study. Peak oxygen consumption (pVO(2)) was collected during semi-supine bicycle exercise. Systolic (GLSRs) and early diastolic (GLSRe) longitudinal strain rate using STE and Doppler echocardiographic parameters were measured at rest, submaximal, peak exercise, and 4 min after exercise. The two groups had comparable resting echocardiographic measurements. At peak exercise, pVO(2) was lower in patients than controls (18.5 +/- 4.5 vs. 22.1 +/- 4.3 L/min/kg, P < 0.05). GLSRs (0.98 +/- 0.28 vs. 1.55 +/- 0.30 1/s, P < 0.001), septal Sm (7.9 +/- 1.4 vs. 11.1 +/- 2.3 cm/s, P < 0.001) and their changes between rest and peak exercise (Delta GLSRs: 0.16 +/- 0.33 vs. 0.68 +/- 0.27 1/s, P < 0.001; Delta Sm 2.29 +/- 2.23 vs. 4.63 +/- 2.29 cm/s, P < 0.01) were significantly lower in patients than controls. There was no correlation between pVO(2) and any echocardiographic measurements in controls. In patients, pVO(2) correlated with peak exercise GLSRs (r = 0.60, P = 0.0007), septal Sm (r = 0.65, P = 0.002), and Em (r = 0.57, P = 0.009). In a multivariate model, peak exercise GLSRs (beta = 7.18, P = 0.03) was the only independent predictor of pVO(2) in the patients group.Conclusion: Exercise capacity is subnormal after AVR for AS, irrespective of normal LVEF suggesting residual compromised myocardial functional reserve.
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