| 1. |
- Hedlund, Anna, et al.
(författare)
-
Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement
- 2011
-
Ingår i: International journal of nano medicine. - Manchester, UK : Dove Medical Press Ltd. - 1178-2013. ; 6, s. 3233-3240
-
Tidskriftsartikel (refereegranskat)abstract
- As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s-1 mM-1 and 9.6–17.2 s-1 mM-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.
|
|
| 2. |
- Anving, Terese, et al.
(författare)
-
Informationskompetens – generella färdigheter för fördjupat lärande
- 2012
-
Ingår i: Proceedings, Lunds universitets utvecklingskonferens 11. - 9789197797467 ; , s. 107-116
-
Konferensbidrag (refereegranskat)abstract
- Förmågan att effektivt utnyttja och kritiskt förhålla sig till olika informationsresurser – ”information literacy” eller informationskompetens – är en central färdighet i det moderna samhället. Det utgör också en allt viktigare del av lärandet i högre utbildning. Syftet med detta paper är tvåfaldigt: 1) att problematisera relationen mellan informationskompetens som en generell färdighet och mer specifika ämnesorienterade kunskaper och färdigheter; 2) ge exempel på och utveckla redskap för lärare att på ett ämnesmässigt integrerat sätt arbeta med, utveckla och examinera studenternas informationskompetens. Ett huvudspår i framställningen är att synliggöra hur träningen i informationskompetens kan stimulera och hjälpa studenterna till fördjupade ämneskunskaper.
|
|
| 3. |
- Cao, Renhai, et al.
(författare)
-
Mouse corneal lymphangiogenesis model.
- 2011
-
Ingår i: Nature protocols. - : Springer Science and Business Media LLC. - 1750-2799 .- 1754-2189. ; 6:6, s. 817-26
-
Tidskriftsartikel (refereegranskat)abstract
- This protocol describes a powerful in vivo method to quantitatively study the formation of new lymphatic vessels in the avascular cornea without interference of pre-existing lymphatics. Implantation of 100 ng of lymphangiogenic factors such as vascular endothelial growth factor (VEGF)-A, VEGF-C or fibroblast growth factor-2, together with slow-release polymers, into a surgically created micropocket in the mouse cornea elicits a robust lymphangiogenic response. Newly formed lymphatic vessels are detected by immunohistochemical staining of the flattened corneal tissue with lymphatic endothelial-specific markers such as lymphatic vessel endothelial hyaluronan receptor-1; less-specific markers such as vascular endothelial growth factor receptor 3 may also be used. Lymphatic vessel growth in relation to hemangiogenesis can be readily detected starting at day 5 or 6 after pellet implantation and persists for ∼14 d. This protocol offers a unique opportunity to study the mechanisms underlying lymphatic vessel formation, remodeling and function.
|
|
| 4. |
- de Vries, Franciska T., et al.
(författare)
-
Soil food web properties explain ecosystem services across European land use systems
- 2013
-
Ingår i: Proceedings of the National Academy of Sciences. - Washington, DC : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:35, s. 14296-14301
-
Tidskriftsartikel (refereegranskat)abstract
- Intensive land use reduces the diversity and abundance of many soil biota, with consequences for the processes that they govern and the ecosystem services that these processes underpin. Relationships between soil biota and ecosystem processes have mostly been found in laboratory experiments and rarely are found in the field. Here, we quantified, across four countries of contrasting climatic and soil conditions in Europe, how differences in soil food web composition resulting from land use systems (intensive wheat rotation, extensive rotation, and permanent grassland) influence the functioning of soils and the ecosystem services that they deliver. Intensive wheat rotation consistently reduced the biomass of all components of the soil food web across all countries. Soil food web properties strongly and consistently predicted processes of C and N cycling across land use systems and geographic locations, and they were a better predictor of these processes than land use. Processes of carbon loss increased with soil food web properties that correlated with soil C content, such as earthworm biomass and fungal/bacterial energy channel ratio, and were greatest in permanent grassland. In contrast, processes of N cycling were explained by soil food web properties independent of land use, such as arbuscular mycorrhizal fungi and bacterial channel biomass. Our quantification of the contribution of soil organisms to processes of C and N cycling across land use systems and geographic locations shows that soil biota need to be included in C and N cycling models and highlights the need to map and conserve soil biodiversity across the world.
|
|
| 5. |
- Eleonora Hedlund, Eva-Maria, et al.
(författare)
-
Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs
- 2013
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:2, s. 654-659
-
Tidskriftsartikel (refereegranskat)abstract
- The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti-VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using plgf shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy.
|
|
| 6. |
- Hagen, Niclas, et al.
(författare)
-
Genetics and democracy-what is the issue?
- 2012
-
Ingår i: Journal of Community Genetics. - : Springer Science and Business Media LLC. - 1868-6001 .- 1868-310X.
-
Tidskriftsartikel (refereegranskat)abstract
- Current developments in genetics and genomics entail a number of changes and challenges for society as new knowledge and technology become common in the clinical setting and in society at large. The relationship between genetics and ethics has been much discussed during the last decade, while the relationship between genetics and the political arena-with terms such as rights, distribution, expertise, participation and democracy-has been less considered. The purpose of this article is to demonstrate the connection between genetics and democracy. In order to do this, we delineate a notion of democracy that incorporates process as well as substance values. On the basis of this notion of democracy and on claims of democratisation in the science and technology literature, we argue for the importance of considering genetic issues in a democratic manner. Having established this connection between genetics and democracy, we discuss this relation in three different contexts where the relationship between genetics and democracy becomes truly salient: the role of expertise, science and public participation, and individual responsibility and distributive justice. As developments within genetics and genomics advance with great speed, the importance and use of genetic knowledge within society can be expected to grow. However, this expanding societal importance of genetics might ultimately involve, interact with, or even confront important aspects within democratic rule and democratic decision-making. Moreover, we argue that the societal importance of genetic development makes it crucial to consider not only decision-making processes, but also the policy outcomes of these processes. This argument supports our process and substance notion of democracy, which implies that public participation, as a process value, must be complemented with a focus on the effects of policy decisions on democratic values such as distributive justice.
|
|
| 7. |
- Hedlund, Anna, 1973-
(författare)
-
MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is an increasing interest for nanomaterials in bio-medical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3 ) have been investigated as a novel contrast agent for magnetic resonance imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as such multimodal contrast agent. Relaxivity measurements show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and an increase in signal intensity in T1-mapped images. The cellular uptake of Gd2O3 nanoparticles were increased with the use of transfection agent protamine sulfate. This work shows that Gd2O3 nanoparticles possess good relaxation properties that are retained in different biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in forinstance cell labeling experiments.
|
|
| 8. |
- Hedlund, Eva-Maria
(författare)
-
The impact of vascular structure and function on tumor growth, retinopathy, and antiangiogenic therapy
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tumors produce multiple angiogenic factors to stimulate neovascularization that is essential for tumor growth, invasion and metastasis. Despite the known angiogenic functions of each individual factor, the interplay between these angiogenic factors in the tumor local environment and in modulation of the host functions remain poorly understood. This thesis addresses these important and complex issues using various in vitro and in vivo experimental models. The findings from these studies provide mechanistic insights on the of complex interplay between various angiogenic factors and on the systemic impact of these tumor-derived factors on the host. In paper I, we showed one of the first examples of two unrelated angiogenic factors, i.e., FGF-2 and PDGF-BB that reciprocally modulate tumor angiogenesis and metastasis. We found that FGF-2 markedly upregulates the expression levels of PDGFRα and β in endothelial cells, leading to the hypersensitive response of these cells toward PDGF-BB stimulation. Reciprocally, PDGF-BB is also able to upregulate the expression level of FGFR-1 in perivascular cells. The angiogenic synergism and vascular remodeling by these two factors markedly accelerates tumor growth rates, leading to an invasive phenotype in a mouse xenograft tumor model. In paper II, we describe a negative interplay between two angiogenic factors that significantly modulate the number and structure of tumor blood vessels. PlGF could negatively modulate VEGF functions by the formation of heterodimers during their synthesis in the same cell. We show that the PlGF-VEGF heterodimers are less potent than VEGF homodimers and thus significantly reduce the angiogenic activity of VEGF. Surprisingly, we found that modulation of the VEGF-induced angiogenic activity by PlGF markedly normalize tumor vessels. PlGF-induced vascular normalization may imply increased therapeutic efficacy of antiangiogenic drugs. In paper III, we showed that tumor-derived VEGF and PlGF can enter into the circulation and systemically impair vascular functions of other tissue and organs. In this paper, we proposed a new mechanism of cancer-associated retinopathy caused by tumor-derived angiogenic factors. Unlike vasculatures distributed in other tissues, the retinal vasculature predominantly expresses VEGFR1, but lacks a detectable level of VEGFR2. Tumor-derived VEGF and PlGF significantly ablate vascular pericytes, leading to increased leakiness of the retinal vasculature. These findings suggest that targeting tumor-derived VEGF, PlGF or other related angiogenic factors might provide a new therapeutic strategy for the treatment of cancer-associated retinopathy, which otherwise remains untreatable. In paper IV, we discovered a new mechanism underlying the combination therapy between antiangiogenic drugs and chemotherapeutics. Based on preclinical findings, we propose that decreased chemotoxicity by antiangiogenic drugs might significantly contribute to survival advantages of patient receiving a combination of these two classes of drugs. We have also rationalized the optimal delivery of these two drugs by using a sequential procedure rather than a simultaneous schedule as currently recommended in clinical settings. Taken together, this thesis work reveals several novel mechanisms of tumor angiogenesis and provides novel information of antiangiogenic therapy, which can be further optimized based on the work reported in this thesis. This thesis work represents translational and that mechanistic studies which can lead to clinically meaningful implications and our eventual goal is to improve survival and the quality of life for millions of cancer patients.
|
|
| 9. |
- Hedlund, Hanna, et al.
(författare)
-
Jämförelse av energirapportering till IEA och UNFCCC
- 2010
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- 1.1 BakgrundSverige rapporterar årligen luftemissioner till UNFCCC (United Nations Framework Convention on Climate Change) i två olika format, dels sectoral approach vilket beräknas från mikrodata i olika sektorer, dels i reference approach som beräknas från bränsleanvändningen i energistatistiken. Klimatrapporteringen granskas av IEA (International Energy Agency) samt av internationella granskarteam, huruvida bränsleanvändningen överensstämmer i reference approach och den energistatistik Sverige rapporterar till IEA. Eftersom även EU måste leverera luftemissioner för EU-totalt till UNFCCC har Eurostat jämfört Sveriges rapporterade reference approach med utsläppsberäkningar gjorda av EU utifrån IEA-data. Granskarna har givit upprepade påpekanden att viss data som rapporterats till UNFCCC enligt reference approach inte överensstämmer med rapporteringen till IEA.I denna rapport beskrivs reference approach (RA) från UNFCCC-rapporteringen och IEA-rapporteringen och skillnaderna däremellan förklaras.1.2 Svar till internationella granskareFör att jämföra de två rapporteringarna räknar IEA om bränslemängderna (m3, ton) i IEA-rapporteringen till energi (TJ). De flesta skillnader som då hittas kan förklaras av att IEA använder standardiserade värmevärden i sina beräkningar och i beräkningarna till UNFCCC-rapporteringen används värmevärden anpassade till svenska förhållanden. När data i naturliga enheter jämfördes mellan rapporteringarna minskade skillnaderna avsevärt och flera differenser eliminerades.Några av de största skillnaderna beror på skillnader i avgränsningar, att bränslen rapporteras under olika rubriker. För några bränsleslag förekom skillnader i beräkningsmetoder, eller att olika datakällor använts. I några fall har revideringar av data skett som inte synts i båda rapporteringarna då data är hämtat vid olika tidpunkter.För internationell bunkring har man i rapporteringen till UNFCCC lagt mer uppmärksamhet på eventuella korrigeringar av tidsserien än vad som görs i IEA-rapporteringen. Anledningen är att UNFCCC har större krav på kontinuitet. Det här gör att siffrorna kan vara olika mellan rapporteringarna.En fullständig beskrivning av skillnaderna för varje bränsleslag presenteras i avsnitt 4.2.1.3 RekommendationerVi rekommenderar att datakällorna och metoderna för ett antal bränslen uppdateras i UNFCCC-rapporteringen, se avsnitt 4.2 för detaljer.Problem har uppmärksammats med att reviderade siffror ibland inte inkommer till UNFCCC-rapporteringen, eller att skillnader förekommer i data för att det hämtats vid olika tillfällen till de olika rapporteringarna och ändringar har skett mellan tillfällena. Vi rekommenderar därför att varje år se över föregående års data för sådana förändringar eller revideringar. Detta skulle innebära merarbete för energienheten på SCB, vilket måste hanteras.Trots att samma värmevärden borde användas av SCB:s miljöenhet (RM/MIT), SCB:s energienhet (RM/ET) och av Energimyndigheten (EM) har inte alltid så skett. När uppdateringar eller förändringar sker är informationskedjan lång. Det tar tid för informationen att nå alla berörda parter, eller det är dålig medvetenhet om vilka de berörda parterna är. 5Energimyndigheten har redan tidigare uppmärksammat detta, och avser att efter sommaren ha ett möte med berörda parter med syfte att åstadkomma en harmonisering av värmevärdena. Om skillnaderna mellan reference approach och sectoral approach, när man tagit hänsyn till bränsle som används i industriprocesser etc, är större än +- 2% måste man ange förklaringar till detta i National Inventory Report (NIR)1. För den svenska rapporteringen överstiger skillnaderna 2% för ett flertal år, vilket visar att det finns problem i underlagsdata. Data i sectoral approach har genomgått ett flertal revideringar och är av mycket hög kvalitet. De dataproblem som finns har sin grund i de data som används i reference approach. Detta beskrivs detaljerat i NIR annex 4.21http://2.2 Rapporterade årTill UNFCCC rapporteras varje år en hel tidsserier från 1990 och framåt. I den submission som rapporterades från Sverige april 2010 ingick data avseende 1990-2008. I submission 2011 kommer data 1990-2009 att ingå. Det förekommer varje år att tidigare års data revideras.När man skall använda data till UNFCCC måste man alltså alltid utgå från den senaste submissionen. Ett av huvudsyftena med att rapportera tidsserier på det här sättet är att säkerställa att tidsserien är helt konsistent, dvs. att de olika utsläppsåren är jämförbara med varandra. Detta är nödvändigt då de rapporterande parterna har åtagit sig att minska sina utsläpp med ett visst antal procent sedan 1990. Dessa minskningar måste vara faktiska minskningar och inte bara något man får intryck av på grund av metodbyte för de senare åren.
|
|
| 10. |
- Hedlund, Maria, et al.
(författare)
-
Democratic expert influence through bioethical advisory commissions? The case of Sweden
- 2010
-
Ingår i: Quality Issues in Clinical Genetic Services. - 9789048139187
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Bioethical government advisory committees have profound influence on political decision-making on gene technology issues, concerning not only patients with genetically related diseases, but also, potentially, the whole society. • Decision-making on issues concerning all society should be democratically legitimate in all aspects, including the work of government advisory committees. • Democratic legitimacy of expert advice is desirable not only for the democratic values per se, but also for the quality of political decisions. • In the case of PGD legislation in Sweden, the national government advisory committee functioned as a bridge between political representatives, specialist civil servants, and scientific experts, but the connection with public opinion was more or less absent. • Had the advisory committee worked more openly and allowed a multiplicity of perspectives being heard, the democratic and quality aspects in this legislation process would have been strengthened.
|
|
