399 research outputs found
Check-list of European Orthoptera
No full textList of all 974 recognized species of Ensifera (Tettigonioidea: 458, Rhaphidophoroidea: 44, Grylloidea: 91) and Caelifera (Tetrigoidea: 12, Tridactyloidea: 6, Acridoidea: 363) in Europe including information about their distribution.Aufstellung aller 974 derzeitig anerkannten Arten der Ensifera (Tettigonioidea: 458, Rhaphidophoroidea: 44, Grylloidea: 91) and Caelifera (Tetrigoidea: 12, Tridactyloidea: 6, Acridoidea: 363) in Europa mit Angabe der Verbreitungsgebiete
Fiscal Consolidation with High Growth : A Policy Simulation Model for India
No full textIn this paper a fiscal consolidation program for India has been presented based on a policy simulation model that enables us to examine the macroeconomic implications of alternative fiscal strategies, given certain assumptions about other macro policy choices and relevant exogenous factors. The model is then used to estimate the outcomes resulting from a possible strategy of fiscal consolidation in the base case. The exercise shows that it is possible to have fiscal consolidation while at the same time maintaining high GDP growth of around 8% or so. The strategy is to gradually bring down the revenue deficit to zero by 2014-15, while allowing a combined fiscal deficit for centre plus states of about 6% of GDP. This provides the space for substantial government capital expenditure, which translates to a significant public investment program. This in turn leads to high overall investment directly and indirectly, via the crowding in effect on private investment, which drives the high GDP growth. The exercise has also tested the robustness of this strategy under two alternative scenarios of higher and lower advanced country growth compared to the base case.Macroeconomic Modelling, Policy Simulation, Fiscal Policy, India
From oncogenic replication stress to drug resistance : F-box proteins as signalling hubs in cancer
No full textCancer arises from cells that acquire genetic and epigenetic changes during the course of a, sometimes decades-long, somatic evolutionary process. These changes result in deregulation of a multitude of cellular processes leading to novel capabilities, often referred to as hallmarks of cancer, and a strong selective advantage for these cells albeit at a dramatic cost to the organism as a whole. Both, gene expression but also turn-over of gene products can become deregulated. The ubiquitin-proteasome system is responsible for the targeted degradation of proteins, and components of this system are altered during cancer development. Target specificity of this system is largely attained through E3 ubiquitin ligases that mediate the covalent attachment of ubiquitin to their substrates. The largest group of E3s are cullin-RING domain ligases (CRLs) with SKP1-cullin1-F-box protein (SCF) E3 ligases, or CRL1, representing one of the best-characterised subgroups of CRLs. These SCF ligases are multiprotein complexes containing one of, in human cells, 69 F-box proteins which function as substrate-adaptor subunits. Collectively, the family of F-box proteins has been found to be critically involved in virtually all the cancer hallmarks. However, despite their important role in cancer development, only a handful of SCFs has been molecularly and functionally well- characterised and detailed knowledge of how deregulation of specific SCF ligases and downstream substrate effectors impinges on cancer traits is lacking.One of the main aims of the work presented in this thesis is to find cellular vulnerabilities resulting from deregulation of F-box proteins in cancer. FBXW7 is the most commonly mutated F-box protein in human cancers. Its inactivation leads to upregulation of its substrates including cyclin E, MYC or SOX9 (paper IV) resulting in deregulated proliferation, increased metastasis and drug resistance but also replication stress. Cancer cells undergoing replication stress become more dependent on signalling pathways detecting and repairing damaged DNA (papers I and III) and are consequently more sensitive to therapies targeting checkpoint and repair proteins such as WEE1, ATR or DNA-PK kinases (paper II).In paper I we describe a novel function for the largely uncharacterised F-box protein FBXL12 in regulating the response to oncogene-induced replication stress. FBXL12 complements the Fanconi anaemia (FA) DNA repair pathway by targeting its central component FANCD2 for proteasomal degradation. The FA pathway not only plays a crucial role in resilience to endogenous sources of replication stress but also to drug-induced stress. FBXL12 and cyclin E are upregulated and correlated in human cancers and depletion of FBXL12 results in increased sensitivity to replication stress which posits FBXL12 as a potential cancer drug target. Ablation or pharmacological inhibition of FBXL12 prevents degradation of FANCD2 and breast cancer cells are sensitised to the adverse effects of drug- as well as oncogenic cyclin E-induced replication stress.In paper II we focus on exploring further ways of sensitising cancer cells to replication stress. We performed a screen to identify potential viability markers in response to replication stress induced by WEE1 inhibitor AZD1775 and discover novel synergistic combinations. Additionally, we determine a subset of basal-like breast cancer cells that responds to treatment initially but recovers after treatment cessation and identify PTEN as a novel predictive marker for such responses, with cells expressing low levels of PTEN being highly sensitive acutely and failing to recover. Furthermore, inactivation or genomic deletion of DNA-PK, an apical DNA damage kinase, attenuates recovery and sensitises basal-like breast cancer cells to AZD1775. Mechanistically, loss of PTEN or DNA-PK impair CHK1 activation and S-phase arrest in response to AZD1775 treatment, which finally ensues lethal replication stress and loss of survival.In paper III we concentrate on FBXO28, another poorly-studied member of the F-box family, which we find to degrade ARHGEF6 and ARHGEF7 activators of the Rho-type GTPase RAC1, involved in cell motility. Surprisingly, we identify a novel function for FBXO28 and ARHGEF6/7 in promoting the repair of breaks in heterochromatin DNA. Following DNA damage, tightly chromatin-bound FBXO28 is released and promotes degradation of nucleoplasmic ARHGEF6/7 to modulate activation and inactivation cycles of nuclear RAC1 and allow for efficient resolution of H3K9me2/3-positive damaged sites.In paper IV we add a key oncogenic transcription factor to the growing list of FBXW7 substrates; SOX9. FBXW7 ubiquitylates and degrades SOX9 upon phosphorylation by GSK3β. Mutation and inactivation of FBXW7 in medulloblastoma concurs with elevated SOX9 protein expression and poor patient outcome. In medulloblastoma cell line models we demonstrate increased cell motility, metastasis and increased resistance to cytostatic treatment after expression of a non-degradable SOX9 mutant. Conversely, inhibition of the PI3K/AKT/mTOR pathway promoted GSK3β-dependent SOX9 degradation and sensitised FBXW7-proficient medulloblastoma cells to cisplatin.List of scientific papersI. Brunner, A.§, Johansson, H., Kourtesakis, A., Viiliäinen, J., Widschwendtner, M., Wohlschlegel, J., Lehtiö, J., Spruck, C., Orre, L.M., Rantala, J. K. and Sangfelt, O.§. Degradation of FANCD2 by SCF-FBXL12 alleviates cyclin E-driven replication stress and maintains genomic integrity. §Corresponding author. [Manuscript]II. Brunner, A.*, Suryo Rahmanto, A.*, Johansson, H.±, Franco, M.±, Viiliäinen, J., Gazi, M., Frings, O., Fredlund, E., Lehtiö, J., Rantala, J. K., Larsson, L.-G. and Sangfelt, O§. PTEN and DNA-PK as determinants of sensitivity and recovery in response to WEE1 inhibitor AZD1775 in human breast cancer. eLife. 2020;9:e57894. *Equal contribution, ±Equal contribution, §Corresponding author. https://doi.org/10.7554/eLife.57894 III. Čermák, L.*§, Brunner, A.*, Baloghová, N., Ueberheide, B., Ng, H.-F., Wohlschlegel, J., Manser, E., Sangfelt, O.±§ and Pagano, M±§. FBXO28 controls nuclear RAC1 activity and safeguards efficient heterochromatin DNA repair by targeting ARHGEF6/7 for degradation. *Equal contribution, ±Equal contribution, §Corresponding author. [Manuscript]IV. Suryo Rahmanto, A.*, Savov, V.*, Brunner, A.±, Sara Bolin, S.±, Weishaupt, H.±, Malyukova, A., Rosén, G., Čančer, M., Hutter, S., Sundström, A., Kawauchi, D., Jones, D. T. W., Spruck, C., Taylor, M. D., Cho, Y.-J., Pfister, S.M., Kool, M., Korshunov, A., Swartling, F. J.§ and Sangfelt, O§. FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma. EMBO J. 35(20): 2192–2212. *Equal contribution, ±Equal contribution, §Corresponding author. https://doi.org/10.15252/embj.201693889 </p
Avoiding Carbon Lock-In: Policy Options for Advancing Structural Change
No full textA major obstacle for the transformation to a low-carbon economy is the risk of a carbon lock-in: fossil fuel-based ('dirty') technologies dominate the market although their carbon-free ('clean') alternatives are dynamically more efficient. We study the interaction of learning-by-doing spillovers and the substitution elasticity between the clean and the dirty sector in an intertemporal general equilibrium model. We find that the substitution possibilities between the two sectors have an ambivalent effect: although a high substitution elasticity requires less aggressive mitigation policies than a low one, it creates a greater lock-in in the absence of regulation. The optimal policy response consists of a permanent carbon tax as well as a learning subsidy for clean technologies. A single policy instrument can also avoid high welfare losses, but a more stringent mitigation target can only be achieved at painful costs. We demonstrate that the policy implication of [Acemoglu et al. 2012] is limited in scope. Our numerical results also highlight that infrastructure provision is crucial to facilitate the low-carbon transformation.structural change, low-carbon economy, carbon lock-in, mitigation policies, learning-by-doing
What remains of monetarism?
No full textIn October 1979 the Federal Reserve, in an attempt to curb double-digit inflation, announced that it would place more weight on monetary aggregates in policy deliberations. This policy shift helped reduce inflation but sent the economy into a recession. Three years later the Fed abandoned monetary targets and returned to targeting the federal funds rate. ; Monetary growth targets currently play no official role in the setting of U.S. monetary policy. Is such disregard justified by the data any more today than it was twenty years ago? This article provides a historical perspective on the development and apparent failure of monetarism as a policy guide. ; The author also explores whether the basic monetarist propositions still hold true for a sample of fifteen countries. The analysis suggests that it is premature to dismiss monetary aggregates as uninformative. The data from the economies studied indicate that, in general, nominal income growth and inflation are positively related to money growth. While these results do not support short-term manipulation of the monetary aggregates to deliver precise control over movements in income and prices, they also do not reject the notion that changes in money growth have important long-term effects on the economy. What the results suggest, therefore, is that failure to acknowledge this empirical fact could lead to undesirable policy consequences.Monetary policy ; Monetary theory
Embeddedness as Condition and Strategy in Contemporary Art and Cultural Production
No full textThis thesis examines the concept of ‘embeddedness’ as condition and strategy in contemporary art and cultural production. Identifying embeddedness as a motif of contextual proximity and a strategy in contemporary art, the thesis proposes immediacy to be the result of intrinsic mediation. The project’s main concern is how embeddedness is contextualised by the current conditions that authors and cultural producers engage with. The primary question is whether and how embeddedness can convey a critical relation to the mediation that it undertakes. These concerns inform and arise from my work as an artist, and my participation in events, some of which I organise. The project claims that embeddedness in art is a critical condition and an editorial concept or a strategic plan that can be set up by the artist.
The investigation begins by looking at conditions of embeddedness by focusing on concepts of subjectivity and by elaborating strategies that I call ‘auto-direction’. For example, concepts of subjectivity are taken up in relation to Richard Serra’s video Boomerang (1974), in which the performer Nancy Holt reflects on her own spoken words, which are fed back with a short delay via microphone and headphones into her ears. Auto-direction, introduced with the example of Steven Spielberg’s initiative of a video diary exchange project between Israeli and Palestinian children, describes the activity of the producer, who self-directs his situated presence. Taking up idioms of embeddedness from artists like Phil Collins, Christian Jankowski and Erik van Lieshout the project examines embeddedness through a comparative analysis between contemporary art, visual culture, media theory, sociology, art theory, psychoanalysis and philosophy. These practices lead to an identification of embeddedness as an author’s immanent exposure, a claim taken up through analysis of theoretical texts and literature by Rosalind Krauss, Jacques Lacan, Jacques Derrida, Gregory Bateson, Hal Foster, Bernard Williams and Alfred North Whitehead
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