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Functional role of non-coding RNAs and extracellular matrix proteins in developmental processes and breast cancer
A better understanding of normal organ development can give deeper insight into which genes are harnessed by aberrant cells during cancer formation and progression. In my thesis, I have investigated two seemingly different, however, related, developmental processes in the breast gland: epithelial-to-mesenchymal transition (EMT) and branching morphogenesis. EMT and its reverse process mesenchymal-to-epithelial transition (MET), are important processes during embryogenesis and in diseases, such as cancer, where evidence suggests that they mediate processes such as cell invasion and formation of metastasis. Branching morphogenesis is an essential developmental process that in the breast gland mostly takes place postnatally. Both processes are widely studied due to their importance in multiple fields. However, the involvement of non-coding RNAs in the regulation of gene expression during EMT and branching morphogenesis has recently been appreciated and is a challenging field of study.
In my experimental approach, I mainly took advantage of a well-defined series of cell lines referred to as the D492 cell lines, which include D492, D492M and D492HER2. D492 is a breast progenitor epithelial cell line and a model for branching morphogenesis. D492M is a non-tumorigenic cell line derived from D492 through endothelial-induced EMT, while D492HER2 is a tumorigenic cell line derived from D492 through oncogene-induced EMT. Together, D492 and D492M represent a unique in vitro cellular model, enabling research on the phenotypic and functional changes occurring during EMT, while D492M and D492HER2 allow us to study differences in tumorigenicity.
The primary aim of this thesis was to study the expression and functional role of non-coding RNAs during branching morphogenesis and EMT in the human breast gland using the D492 and D492M cell lines. The secondary aim was to study the role of extracellular matrix proteins secreted by D492HER2 on cancer growth and angiogenesis.
In paper #I, I addressed the role of non-coding RNAs from the DLK1-DIO3 locus in cellular plasticity, EMT and cancer. Here I used primary cells, cancer patient's cohorts and the D492 cell lines. Using the CRISPRi and CRISPRa approaches, we found out that this locus is a marker of mesenchymal cells and affects the cellular plasticity of adult breast epithelial cells.
Paper #II was focused on identifying miRNAs highly upregulated in D492 during branching morphogenesis but downregulated in D492M. We identified MIR203a as a novel suppressor of peroxidasin (PXDN), a collagen IV crosslinking agent. Our results indicate that MIR203a may be an essential regulator of branching morphogenesis and basement remodelling in the human breast gland, likely through its target PXDN.
Finally, in paper #III and IV, we compared the two D492 derived cell lines D492M and D492HER2. Compared to D492M, the tumorigenic D492HER2 has a partial EMT phenotype, seen by increased expression of epithelial miRNAs. D492HER2 shows higher migratory, invasive, proliferative and angiogenic properties compared to both D492 and D492M. By means of mass spectrometry and RNA sequencing analysis of D492M and D492HER2, we identified extracellular matrix protein YKL-40 and ECM1 as potential candidates contributing to tumorigenicity of D492HER2 and to be partially responsible for the functional differences between the cell lines. Moreover, we showed that ECM1 induces crosstalk with endothelial cells through Notch signalling.
Collectively, I have in my thesis partially uncovered the role of non-coding genes from the DLK1-DIO3 locus and MIR203a in EMT and branching morphogenesis. Furthermore, I have also, in collaboration with my co-workers, identified the ECM proteins YKL-40 and ECM1 as potential inducers of cancer growth and angiogenesis.Þekking á þroskun og sérhæfingu vefja gefur innsýn í gen og þroskunarferli sem einnig gegna hlutverki við myndun krabbameina og framþróun æxlisvaxtar. Í þessari ritgerð rannsakaði ég RNA sameindir sem ekki tjá fyrir próteinum (e. non-coding RNAs (microRNA og long noncoding RNA, lncRNA)) og hlutverk þeirra í þroskun og sérhæfingu brjóstkirtilsfruma. Ég skoðaði einkum hlutverk þeirra í bandvefsumbreytingu þekjufruma (e. epithelial to mesenchymal transition, EMT) og í greinóttri formgerð (e. branching morphogenesis). Auk þess rannsakaði ég hlutverk utanfrumupróteina í hegðun og svipgerð brjóstrabbameinsfruma og í nýæðamyndun. EMT og þekjuvefsumbreyting bandvefsfruma (e. mesenchymal to epithelial transition, MET) eru mikilvægir ferlar í fósturþroska og í sjúkdómum á borð við krabbamein þar sem þeir hafa verið tengdir við ífarandi vöxt og meinvarpamyndun. Greinótt formgerð í brjóstkirtlinum hefst að mestu við kynþroska kvenna og er kirtilinn í mikilli ummyndun í hverjum tíðarhring fram að tíðahvörfum. EMT og MET gegna mikilvægu hlutverki í myndun greinóttrar formgerðar í brjóstkirtli. Á síðustu árum hefur komið í ljós að non-coding RNAs hafa mikil áhrif á stjórnun EMT og MET þó enn sé margt á huldu varðandi hlutverk einstakra RNA sameinda í þessu ferli.
Rannsóknarmódelið sem ég notaði byggir á brjóstþekjufrumulínunni D492 og dótturlínum hennar. D492 er stofnfrumulína sem getur myndað greinótta formgerð í þrívíðri rækt. D492M er bandvefs-lik dótturlína frá D492 sem hefur undirgengist EMT. D492HER2 er einnig komin frá D492, en í þessari dótturlínu er HER2 æxlisgenið yfirtjáð; frumulína þessi getur myndað æxli í músum. Þessar línur hafa allar sama erfðabakgrunn en ólíka svipgerð og eru því hentugar til rannsókna á greinóttri formgerð, EMT og MET í eðlilegum og illkynja brjóstkirtli.
Meginmarkmið verkefnisins var að rannsaka tjáningu og hlutverk RNA sameinda sem ekki tjá fyrir próteinum, bæði microRNA og lncRNA, í greinóttri formgerð, EMT og MET í brjóstkirtli. Jafnframt var markmiðið að rannsaka áhrif utanfrumupróteina sem seytt er frá D492HER2 á æxlisvöxt, svipgerð og nýæðamyndun í frumurækt.
Í grein I kannaði ég hlutverk RNA sameinda sem eru staðsett á DLK1-DIO3 genasvæðinu (e. gene locus) á litningi 14 í EMT/MET, stjórnun svipgerðar frumna og í brjóstakrabbameinum. Helstu niðurstöður sýndu að RNA sameindir þessar, þar með talið MEG3 lncRNA og microRNA á þessu genasvæði eru meira tjáð í bandvefsfrumum en þekjufrumum og jafnframt að tjáning þessara RNA sameinda hefur áhrif á sérhæfingu brjóstaþekjufruma yfir í bandvefsfrumur.
Í grein II var markmiðið að greina tjáningamynstur microRNA sameinda í greinóttri formgerð í þrívíðri rækt og EMT. Niðurstöður okkar sýna að tjáning microRNA 203a jókst margalt við myndun greinóttrar formgerðar í D492 en var lækkuð í D492M bandvefsfrumulínunni. Við sýndum einnig fram á að sameindin bælir tjáningu peroxidasin (PXDN) millifrumupróteinsins. Niðurstöður okkar benda til þess að microRNA203a sé mikilvægur stýrill við myndun greinóttrar formgerðar og í myndun grunnhimnu í brjóstkirtli og þá mögulega í gegnum PXDN.
Í grein III og IV var markmiðið að bera saman svipgerð D492 og D492M við D492HER2 frumulínuna sem ólíkt þeim fyrrnefndu myndar æxli í ónæmisbældum músum. Ólíkt D492M, sem hefur sterka EMT svipgerð, þá sýnir D492HER2 einungis EMT svipgerð að hluta (e. partial EMT) og breytir sinni svipgerð eftir ytri aðstæðum, ásamt því að tjá mun meira af þekjuvefstengdum microRNA sameindum en D492M. Auk þess sýnir D492HER2 mun meira skrið og ífarandi vaxtareiginleika en D492M. Með massagreiningu og RNA raðgreiningu greindum við utanfrumupróteinin YKL-40 og ECM1 sem prótein sem mögulega geta stuðlað að krabbameinseiginleikum D492HER2. Jafnframt hafa YKL-40 and ECM1 áhrif á nýmyndun æða í frumuræktunum.
Í ritgerð þessari hef ég rannsakað RNA sameindir sem ekki tjá fyrir próteinum frá DLK1-DIO3 genasvæðinu ásamt microRNA203a og hlutverk þeirra í greinóttri formgerð og í krabbameinum og sýnt fram á að þessar RNA sameindir gegna hlutverki í EMT/MET. Jafnframt hef ég unnið að rannsóknum á hlutverki YKL-40 og ECM1 utanfrumupróteinanna í brjóstakrabbameinum og sýnt fram á hlutverk þeirra í í skriði æxlisfruma og í nýæðamyndun.Landspitali University Hospital - Science Fund, University of Iceland - Research Fund, Rannis - Grant of Excellence, "Vísindasjóður Krabbameinsfélagsins" and "Göngum saman
Second Malignancies in Patients with Multiple Myeloma: Risk Factors and Impact on Survival
Inngangur: Með tilkomu áhrifaríkari lyfja í meðhöndlun sjúklinga með
mergæxli síðastliðna áratugi hefur lifun þeirra stóraukist. Þessi aukna lifun
hefur leitt til aukinnar áherslu rannsakennda á langtíma afleiðingum í formi
þróun annarra krabbameina. Sjúklingar með mergæxli eru í aukinni áhættu á
að þróa með sér ákveðnar tegundir krabbameina svo sem bráða hvítblæði og
mergmisþoska. Undirliggjandi ástæður þessa eru óljósar og áhættuþættir lítt
þekktir. Vísindamenn telja að ástæður seinni krabbameina hjá sjúklingum
með mergæxli séu líklega fjölþættar og samanstandi af þáttum sem tengjast
meðferð, sjúkdómnum sjálfum, erfðum, umhverfinu og lífsstíl. Meginmarkmið
þessarar ritgerðar var að kanna áhrif annarra krabbameina á lifun sjúklinga
með mergæxli og leitast er við að kanna áhættuþætti fyrir þróun þeirra með
sérstaka áherslu á bráðahvítblæði og mergmisþroska.
Efniviður og aðferðir: Við framkvæmdum lýðgundaða rannsókn þar sem
notast var við gögn frá sænsku krabbameinsskránni sem samanstóð af öllum
sjúklingum sem greinst höfðu með mergæxli í Svíþjóð á tveimur mismunandi
tímabilum, annars vegar frá 1. janúar 1958 til 31. december 2011 (n=26,627)
og hins vegar frá 1. janúar 1973 til 31. desember 2010 (n=19,791). Úr fyrri
hópinn fundum við alla sjúklinga sem höfðu greinst með annað krabbamein
eftir mergæxlisgreiningu (n=1,547). Þeir voru paraðir eftir aldri, kyni og
dagsetningu mergæxlisgreiningar við einn til þrjá mergæxlissjúklinga, sem
ekki höfðu þróað með sér annað krabbamein, og þeir valdir með slembiúrtaki
(n=4,019). Við úrvinnslu gagnanna var meðal lifun sjúklinga milli þessarra
tveggja hópa borin saman með Cox líkani. Til þess að kanna áhættuþætti
fyrir bráðahvítblæði/mergmisþoska sértaklega fundum við þá einstaklinga
sem höfðu geinst með bráðahvítblæði/mergmisþoska úr fyrri hópnum (n=124)
og pöruðum við einn sjúkling sem ekki hafði þróað með sér annað
krabbamein. Nákvæmar upplýsingar um meðferð og rannsóknarniðurstöður
við greiningu, meðal annars blóðrannsóknir og niðurstöður
beinmergsskoðunar voru skráðar úr sjúkraskrám. Útsetning fyrir
samanlögðum skammti lyfjameðferðar fyrir hvert lyf var borin var saman milli
hópa ásamt rannsóknarniðurstöðum við greiningu með einhliða
fervikagreiningu, Kí-kvaðratsprófi og Kruskal-Wallis prófi. Við könnuðum
samanlagða skammta af melphalani milli hópa með lógistískri
aðhvarfsgreiningu. Þýði úr seinni hópnum var notað til að kanna áhrif fyrra
krabbameins á þróun annarra krabbameina eftir mergæxlisgreiningu. Áhætta
á að þróa með sér annað krabbamein eftir mergæxlisgreiningu var borin saman milli sjúklinga sem höfðu greinst með krabbamein fyrir
mergæxlisgreiningu og þeirra sem höfðu ekki sögu um fyrra krabbamein með
Cox líkani.
Niðurstöður: Þróun annars krabbameins í sjúklingum með mergæxli var
tengt verri horfum (HR 2.3; 95% CI 2.1-2.5). Meðaltals lifun var 1.1 ár (95%
CI 1.0-1.2) eftir annað krabbamein og 3 ár (95% CI 2.8-3.1) fyrir
mergæxlissjúklinga sem ekki höfðu þróað með sér annað krabbamein
(p<0.001). Við sýndum fram á, að þrátt fyrir aukna lifun á árunum 2001-2011
þá eru áhrif annarrra krabbameina á lifun þessara sjúklinga mikil því þeir
sjúklingar sem greindust eftir aldarmótin með annað krabbamein höfðu
skertar lífslíkur samanborið við sjúklinga sem greindir voru fyrir aldarmótin og
höfðu ekki greinst með annað krabbamein (1958-2000) (HR 1.1; 95% CI 1.1-
1.5). Við sýndum fram á að lifun sjúklinga með mergæxli sem þróa með sér
bráðahvítblæði/mergmisþoska er sérstaklega slæm og þeir eru í 70% aukinni
áhættu á að deyja borið saman við sjúklinga með bráðahvítblæði/
mergmisþoska sem ekki höfðu sögu um fyrra krabbamein. Við fundum
jákvætt samband milli sögu um fyrra krabbamein og þróun annars
krabbameins eftir mergæxlisgreiningu (HR 1.4; 95% CI 1.2-1.7) sem gæti
bent til erfðafræðilegs þáttar í þeirri þróun. Við fundum að fyrra krabbamein
hafði neikvæð áhrif á lifun (HR 1.2; 95% CI 1.1-1.3) og að þeir sjuklingar sem
greindust með fleiri en eitt fyrra krabbamein höfðu enn verri horfur (HR 1.3;
95% CI 1.2-1.5). Hærri samanlagður skammtur af melphalan lyfjameðferð
tengdist aukinni áhættu á þróun bráðahvítblæðis/mergmisþoska (OR 2.8;
95% CI 1.7-5.2). Miðgildistími frá mergæxlisgreiningu fram að greiningu á
bráðahvítblæði/mergmisþoska var 3.8 ár (IQR 2.8-5.8). Við fundum ekki
samband milli þróunnar bráðahvítblæði/mergmisþoska og eftirfarandi
sjúkdómsþátta: M-prótein ísótýpu, blóðleysi, nýrnabilun, kalkofhleðslu og
beinúrátu.
Ályktun: Niðurstöður þessara lýðgrunduðu rannsókna gefa til kynna að
meðferðartengdir og erfðarfræðilegir þættir eiga mögulega þátt í þróun
annarra krabbameina hjá sjúklingum með mergæxli. Skert lifun þessara
sjúklinga undirstrikar mikilvægi þess að greina áhættuþætti og líffræðilega
ferla sem valda þessari þróun. Aukin þekking á áhættuþáttum og orsökum
annarra krabbameina hjá sjúklingum með mergæxli gæti haft áhrif á
leiðbeiningar varðandi eftirfylgd og ákvarðanartöku um mismunandi meðferðir
í framtíðinni.Introduction: Over the past two decades, increased access to modern
effective therapies has improved survival and clinical outcomes for patients
with multiple myeloma (MM). However, improved survival has led to concerns
regarding long-term complications such as development of second
malignancies. Patients with MM have been found to have increased risk of
developing certain types of second malignancies such as acute myeloid
leukemia (AML) and myelodysplastic syndromes (MDS) although exact
biological mechanisms and risk factors are not well-established. A
multifactorial model has been proposed to explain the etiology of second
malignancies in MM patients, possibly including treatment-, host-, disease-,
environmental-, and lifestyle-related factors. The overall aim of this thesis
was to determine the effects of second malignancies on survival in patients
with MM and identify risk factors for second malignancy development with
focus on patients who develop AML/MDS.
Methods: Data was obtained on all patients diagnosed with MM in Sweden
reported to the Swedish Cancer Registry, for two different time periods. The
first cohort included patients diagnosed from January 1,1958 to December
31, 2011 (n=26,627) and the second included patients diagnosed from
January 1, 1973 to December 31, 2010 (n=19,791). In the first cohort, we
subsequently identified all patients with MM who developed a second
malignancy (n=1,547) and randomly matched them by age, sex and date of
MM diagnosis with one to three MM patients who had not developed a
second malignancy (n=4,019). Median overall survival (OS) was compared
between the groups using the Kaplan-Meier method. Cox proportional hazard
model for matched data was used to calculate hazard ratios (HRs) and 95%
confidence intervals (CIs). We looked further into the clinical implication of
AML/MDS by comparing survival in patients with MM and subsequent
AML/MDS to patients with de novo AML/MDS. To identify risk factors for
AML/MDS specifically, patients who developed AML/MDS from the first MM
cohort were identified (n=124) and matched to one patient without a
subsequent second malignancy diagnosis. Detailed clinical and treatment
data was obtained from medical records located at >50 hospitals in Sweden.
Exposure to treatment, including cumulative doses of alkylating
chemotherapy was compared between the groups as well as baseline
disease-related factors by using one-way ANOVA, Chi-Square, and KruskalWallis tests. We further investigated cumulative melphalan exposure between cases and controls, reported as odds ratios (OR). The second cohort was
used to assess impact of prior malignancies on second malignancies and
survival. All cancer diagnoses prior to and after the MM diagnosis were
identified. Prior malignancy was hypothezised to be a proxy for inherent
gentetic susceptibility (host-related factor). Risk of developing a second
malignancy and survival was compared between patients with MM who had a
history of a prior malignancy diagnosis compared to MM patients who did not,
using a Cox proportional hazard model.
Results: Second malignancy development was associated with inferior
surivival in patients with MM (HR 2.3; 95% CI 2.1-2.5). Median OS was 1.1
years (95% CI 1.0-1.2) after a second malignancy diagnosis and 3.0 years
(95% CI 2.8-3.1) for MM patients without a second malignancy (p<0.001). We
found that despite the survival improvement seen in 2001-2011, the impact of
second malignancies is such that patients diagnosed after the millennia had a
worse outcome than patients without second malignancies before the
introduction of modern MM therapy (1958-2000; HR 1.3; 95% CI 1.1-1.5). We
observed that patients with the combination of MM and subsequent
AML/MDS have a dismal outcome, and a 70% higher risk of dying when
compared to patients with de novo AML/MDS. History of prior malignancy
was associated with increased risk of developing subsequent malignancy
(HR 1.4; 95% CI 1.2-1.7), suggesting a possible role of inherent genetic
susceptibility. Additionally, we found that prior malignancy negatively impacts
survival (HR 1.2; 95% CI 1.1-1.3) and that more than one prior malignancy
reduces survival even further (HR 1.3; 95% CI 1.2-1.5). Higher cumulative
melphalan exposure was associated with increased risk of developing
AML/MSD (OR 2.8; 95% CI 1.7-5.2). The median time to AML/MDS
development was 3.8 years (IQR 2.8-5.8). We showed that the risk of
AML/MDS was not statistically altered by M protein isotype, anemia, renal
failure, hypercalcemia, or lytic bone lesion.
Conclusion: The results of our studies suggest that treatment- and hostrelated factors might play a role in second malignancy development in MM
patients. Our findings of inferior survival in patients with second malignancies
highlight the importance of identification of risk factors as well as biological
mechanisms that result in second malignancies. Increased knowledge of
second malignancy risk in MM patients could affect surveillance protocols
and treatment decisions in the future
Optimal Control of Magnetization Reversal in a Monodomain Particle by Means of Applied Magnetic Field
Post-print (lokagerð höfundar)A complete analytical solution to the optimal reversal of a macrospin with easy-axis anisotropy is presented. An optimal control path minimizing the energy cost of the reversal is identified and used to derive the time-dependent direction and amplitude of the optimal switching field. The minimum energy cost of the reversal scales inversely with the switching time for fast switching, follows exponential asymptotics for slow switching, and reaches the lower limit proportional to the energy barrier between the target states and to the damping parameter at infinitely long switching time. For a given switching time, the energy cost is never smaller than that for a free macrospin. This limitation can be bypassed by adding a hard anisotropy axis that activates the internal torque in the desired switching direction, thereby significantly reducing the energy cost. A comparison between the calculated optimal control path and minimum energy path reveals that optimal control does not translate to the minimization of the energy barrier but signifies effective use of the system’s internal dynamics to aid the desired magnetic transition.This work was funded by the Russian Science Foundation (Grant No. 19-72-10138), the Icelandic Research Fund (Grant No. 184949-052), the Deutsche Forschungsgemeinschaft (DFG Grant No. BE2464/17-1), and the Alexander von Humboldt FoundationPeer Reviewe
Experimental identification of two distinct skyrmion collapse mechanisms
Post-print / Lokaútgáfa höfundarMagnetic skyrmions are key candidates for applications in memory, logic and neuromorphic computing. An essential property is their topological protection that is caused by the swirling spin texture and described by a robust integer winding number. However, this protection is strictly enforced only in the continuum, and so the atomic lattice present in all real materials leaves a loophole for switching the winding number. Hence, understanding the microscopic mechanism of this unwinding is crucial for enhancing the stability of skyrmions. Here we use spin-polarized scanning tunnelling microscopy to locally probe skyrmion annihilation by individual hot electrons. We tune the collapse rate by up to four orders of magnitude by using an in-plane magnetic field, and observe distinct transition rate maps that either are radial symmetric or exhibit an excentric hotspot. We compare these maps to atomistic spin simulations based on parameters obtained from first-principles calculations and find that the maps are explained by a radial symmetric collapse at zero in-plane magnetic field and a transition to the recently predicted chimera collapse at finite in-plane magnetic fields. These insights into the transient state of the skyrmion collapse will enable future enhancement of skyrmion stability and designs for intentional skyrmion switches.We gratefully acknowledge helpful discussions with S.
Lounis, S. Bl¨ugel, G. Volovskiy, A. Schlenhoff, M. Liebmann, M. A. Goerzen, T. Sigurj´onsd´ottir and financial support by the German Science Foundation (DFG) via PR 1098/1-1, the Russian Science Foundation (Grant No.19-72-10138), the Icelandic Research Fund (Grant No.184949-052), and the Alexander von Humboldt FoundationPeer Reviewe
A life-cycle analysis of deep enhanced geothermal systems – The case studies of Reykjanes, Iceland and Vendenheim, France
The climate impacts of deep enhanced geothermal systems (EGS) have been understudied in the academic literature. Using life-cycle analysis (LCA) conducted in accordance with ISO 14040 and ISO 14044 standards, this paper explores the climate change impacts of two deep EGS. The first study was in Reykjanes, Iceland, where a single well, IDDP-2/DEEPEGS, was drilled to a depth of 4.6 km for the purposes of additional electricity production from an existing power plant. The second study involved two wells with side-tracks (depth > 5000 m), drilled to serve a new heat and power co-generation plant located on an old oil field site in Vendenheim, France. Climate change impacts for the sites were estimated in the range 1.6–17.4 gCO2e/kWh and 6.9–13.9 gCO2e/kWh for Reykjanes and Vendenheim, respectively. Although the EGS projects are very different, both outcomes are low when compared to non-renewable alternatives and akin to best-in-class renewable alternatives. The main impact at the Reykjanes demonstration site were the greenhouse gas emissions released from the borehole, an effect that could be avoided by carbon capture and storage/mineralisation/utilisation. In the case of Vendenheim, further reductions in emissions could be achieved via more extensive adoption of circular economy principles in design and procurement.Peer Reviewe
An appraisal of interlinkages between macro-economic indicators of economic well-being and the sustainable development goals
Recognising the well-known limitations of economic growth as a litmus test of progress and the call by Target 19 of Sustainable Development Goal (SDG) 17 to “develop measurements on progress on sustainable development that complement gross domestic product”, this paper advances understanding of the linkages between alternative measures of economic well-being, the well-being economy and the SDGs. A conceptual model is presented, linking four capital assets to well-being goals and domains, which are connected to related SDGs. An assessment is conducted on the extent to which Gross Domestic Product and five alternative indicators of economic well-being (Environmentally Adjusted Net Domestic Product, Measure of Economic Welfare, Genuine Savings, Genuine Progress Indicator and Inclusive Wealth Index) align with (a) the dimensions of economic well-being, and (b) various environmental, economic, social and institutional targets set by the SDGs. The Genuine Progress Indicator (GPI) is found to be the most comprehensive in coverage, accounting for market-based welfare, services from essential capital, and various environmental and social costs, and linking directly to targets in fourteen of the seventeen SDGs. The paper discusses how greater use of alternative measures of economic well-being by policymakers can encourage transitions to economies which prioritise well-being and desirability objectives.The main author, David Cook, is in receipt of a Post-Doctoral Fellowship Grant from the University of Iceland
Careers of Doctorate Holders: A Study of the Gendered Context of Family Dynamics and Earnings
At the international level, Iceland is faring well on gender assessments
concerning economic status, political position, education, and health. However,
despite the ambitious goal of the Icelandic Government to fully reach gender
equality, the gender pay gap prevails. Education is considered crucial in
mitigating this pay gap. In Iceland, the percentage of female doctorate holders
has been steadily increasing, however, little attention has been given to how
gender may affect the interplay between work–family balance, career making,
and earnings of doctorate holders.
This dissertation is one of the outcomes of the NORDICORE research
collaboration. The objective of the thesis is to obtain a better understanding of
the gendered differences in career making among doctorate holders in Iceland,
using both quantitative and qualitative methods. By utilizing Statistics Iceland’s
longitudinal individual register-based census data of the period between 1997
and 2017, we were able to identify all individuals who obtained a doctorate
degree in the fields of science, technology, engineering, and mathematics as
well as social sciences and humanities between 1997 and 2013. The year 2017
is set as the baseline, which is the point in time when the identified individuals
held 5- to 20-year-old doctorate degrees (N=814). A special focus was aimed at
investigating possible inequalities in earnings of doctorate holders, with a
particular focus on how gender, field of study, employment within or outside
academia, and family transitions such as childbirths and periods of parental
leave influence career development through period of up to 20 years.
Furthermore, 32 in-depth interviews were conducted with individuals from the
same pool of doctorate holders to understand people’s perceptions on
possibilities and constraints regarding their career-making and examine how
various family elements, such as having children and running a household, were
influencing, or had influenced, their choices and decision-making throughout their careers. The extensive family policies provided by the Icelandic
government, designed to help facilitate equal rights for men and women within
the labor force as well as to provide better opportunities for women to advance
their career, have contributed to Iceland reaching a higher level of gender
equality compared with many other countries. Therefore, Iceland provides an
interesting setting to research gender (in)equality from another starting point
than previous studies.
The findings from the quantitative phase of the study reveal—despite
Iceland’s reputation as a ‘gender-equality-paradise’—a continuous gender pay
gap among Icelandic doctorate holders through a 20-year period. This applies
regardless of field of study or the employment being within or outside
academia. Not only do male doctorate holders earn significantly more than their
female counterparts, but having children positively impacts men’s earnings
whereas for women, children start to have a negative impact 10 years after
graduation. Furthermore, the findings from the qualitative phase reveal that
male doctorate holders generally felt a higher level of agency regarding their
work–family balance and time management compared with female doctorate
holders who more often expressed difficulties in finding a proper balance and
expressed being more stressed about the often-fragmented time they had to
combine their career and family obligations successfully. The findings further
underline that the widely accepted notion of women’s education as a tool for
closing the gender gap and the widely known reputation of Iceland as a
“gender-equality-paradise” in some ways serves as a façade behind which the
more accepted, traditional gendered functions disappear. Although the
traditional male breadwinner model is assumed to be outdated in Icelandic
society, some of its pillar thoughts still persist beneath the surface, also among
doctorate holders. In such an environment, cultural habits, such as the
traditional division of labor at home, are more easily portrayed as individualistic
choices or agreements between partners. Moreover, the gender power divisions
within the home also stay in place, negatively and continuously affecting the careers and finances of women. Therefore, it can be concluded that equality promoting
legislation—despite contributing to changing norms and values to
some extent—is not by itself sufficient to fully improve gender equality within
the organizational environment of workplaces or the gendered power relations
between partners, coupled with traditional gendered identities/gender roles. A
constant discussion on both the organizational and societal levels of deeply
embedded gendered cultural values and ideas is also required.This work was supported by NordForsk [grant number 80713] and The Eimskip University Fund [grant number 1010-101352]
Long‐term warming effects on the microbiome and <i>nifH</i> gene abundance of a common moss species in sub‐Arctic tundra
Bacterial communities form the basis of biogeochemical processes and determine plant growth and health. Mosses harbour diverse bacterial communities that are involved in nitrogen fixation and carbon cycling. Global climate change is causing changes in aboveground plant biomass and shifting species composition in the Arctic, but little is known about the response of moss microbiomes in these environments.
Here, we studied the total and potentially active bacterial community associated with Racomitrium lanuginosum, in response to 20-year in situ warming in an Icelandic heathland. We evaluated the effect of warming and warming-induced shrub expansion on the moss bacterial community composition and diversity, and nifH gene abundance.
Warming changed both the total and the potentially active bacterial community structure, while litter abundance only affected the total bacterial community structure. The abundance of nifH genes was negatively affected by litter abundance. We also found shifts in the potentially nitrogen-fixing community, with Nostoc decreasing and non-cyanobacterial diazotrophs increasing in relative abundance.
Our data suggests that the moss microbial community and potentially nitrogen fixing taxa are sensitive to future warming, partly via changes in litter and shrub abundance.H2020 Marie Skłodowska-Curie ActionsPost-print (lokagerð höfundar
Electric vehicles, a silver bullet or merely a piece to the puzzle of an intergenerationally sustainable urban mobility sector?
Globally, electric vehicles (EVs) are being touted by countries and international organizations as a key transition technology to decarbonize the road transport sector. Yet, other researchers have suggested that EVs may not be a silver bullet solution, and public debates frequently question the embedded environmental impacts of EV’s battery packs, electricity source, and potential to add to peak load, thus challenging grid systems and potentially requiring greater electrical generation capacity. EVs can be considered a technological solution to decarbonizing the urban transport sector, and studies have pointed out the need to consider both behavioural (demand-side) and technological approaches.
This thesis attempts to address these challenging questions regarding EV integration through a multi-layered approach in which EVs are assessed at a product and urban level in terms of greenhouse gas (GHG) emissions and electricity grid peak load impacts. Lastly, the thesis aims to characterize an intergenerationally ‘safe and just’ urban mobility system to contextualize the discussion surrounding EVs within a global sustainability framework, allowing for interpretation of what development pathways may provide the best results in terms of sustainability.
Intending to expand the conversation surrounding EVs, the results of the thesis suggest that a large-scale integration of EVs without car fleet reductions and other Avoid-Shift-Improve strategies may not be sufficient for achieving this intergenerational ‘safe and just’ sustainability. Rather than taking an EV-centric technological approach, it is suggested that accessibility and behavioural approaches should be equally considered, with the approach taken relevant to the context of the urban area in question when attempting to decarbonize a region’s road transport sector. Thus, rather than seeing EVs as a silver bullet, this research suggests that they should seen as a single potential solution within a suite of solutions that should be used in the right context (i.e. low carbon electrical grid intensity and situations where the accessibility, travel distance, and public/active transport modes cannot provide sufficient mobility provisioning). It is the aim of this thesis that the results of this work can be used to inform policy makers and urban planners of the value of taking balanced supply- and demand-side solution approaches relevant to the local context and help them develop more sectorally-focused policies tied to sectorally characterized ‘safe and just’ state to help guide the urban mobility sector towards intergenerational sustainability.Á heimsvísu eru rafknúin farartæki (EVs) kynnt af löndum og alþjóðastofnunum sem
lykiltæki í umbreytingunni til að minnka losun í vegaflutningum. Samt hafa vísindamenn
gefið til kynna að rafbílar séu kannski ekki besta lausnin og opinber umræða efast oft um
innbyggð umhverfisáhrif rafhlaðna, raforkugjafans og möguleika á að auka á hámarksálag
og storka þannig rafmagnskerfinu sem geti krafið meiri raforkuframleiðslu. Líta má á rafbíla
sem tæknilausn til að draga úr kolefnislosun í flutningageiranum í þéttbýli og rannsóknir
hafa bent á nauðsyn þess að huga að hegðunaraðferðum (eftirspurnarhliðinni) og tæknilegum
aðferðum.
Þessi ritgerð reynir að takast á við þessar krefjandi spurningar varðandi samþættingu rafbíla
með marglaga nálgun þar sem rafbílar eru metnir á vöru- og þéttbýlisstigi með tilliti til
losunar gróðurhúsalofttegunda (GHG) og áhrifa á hámarksálag raforkunetsins. Loks miðar
ritgerðin að því að einkenna „öruggt og réttlátt“ hreyfanleikakerfi í þéttbýli milli kynslóða
til að setja umræðuna um rafbíla í samhengi innan alþjóðlegs sjálfbærniramma, sem gerir
kleift að túlka hvaða þróunarleiðir geta gefið bestan árangur hvað varðar sjálfbærni.
Niðurstöður ritgerðarinnar er ætlað að bæta við umræðuna um rafbíla og benda á að stórfelld
aukning rafbíla án þess að minnka bílaflota og aðrar avoid-shift-improve aðferðir gæti ekki
verið nægjanleg til að ná fram þessari „öruggu og réttlátu“ sjálfbærni milli kynslóða.
Í stað þess að nota rafbílamiðaða tækninálgun er lagt til að aðgengis- og hegðunaraðferðir
verði jafnt skoðaðar í samhengi við viðkomandi þéttbýli þegar reynt er að minnka
kolefnislosun vegasamgangna á því svæði.
Þess vegna, frekar en að líta á rafbíla sem silfurkúlu, benda þessar rannsóknir til að rafbílar
séu aðeins ein möguleg lausn innan mengis fjölda lausna sem ætti að nota í réttu samhengi
(þ.e. lágt kolefnisrafmagnsstyrkur og aðstæður þar sem aðgengi, fjarlægðir og aðrir
flutningsmátar geti ekki veitt nægjanlegan hreyfanleika).
Markmið þessarar ritgerðar er að hægt sé að nota niðurstöður hennar til að upplýsa
stefnumótendur og borgarskipulagsfræðinga um gildi þess að fara leið sem tekur mið af bæði
framboðs- og eftirspurnarhliðinni sem tekur einnig tillit til staðbundins samhengis ásamt því
að hjálpa þeim einstaklingum að þróa með sér nálgun sem byggi á sectorally-focused nálgun
sem einkennist af „öruggri og réttlátri“ nálgun sem ætlað er að hjálpi við hreyfanleika í
þéttbýli í átt að sjálfbærni milli kynslóða.the Icelandic research council (RANNIS) [grant number 185497-051, 2019]
Icelandic Road Authority (Vegagerðin