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A Robust Screening Assay For Diamond Blackfan Anemia Candidate Drugs
Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes
BackgroundCongenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. t
Effect of a 3-year lifestyle intervention on telomere length in participants from PREDIMED-Plus : A randomized trial
Background & aims: Short telomeres have been observed in chronic disease patients. Identifying environmental and lifestyle factors that could reduce telomere attrition is crucial for disease prevention. The aim of this work was to determine whether weight-loss induced by an energy-reduced Mediterranean diet (erMedDiet) and physical activity (PA) could modify telomere length (TL). Methods: In 3
Synthesis of phosphine derivatives of [Fe2(CO)6(μ-sdt)] (sdt = SCH2SCH2S) and investigation of their proton reduction capabilities
The reactions of [Fe2(CO)6(μ-sdt)] (1) (sdt = SCH2SCH2S) with phosphine ligands have been investigated. Treatment of 1 with dppm (bis(diphenylphosphino)methane) or dcpm (bis(dicyclohexylphosphino)methane) affords the diphosphine-bridged products [Fe2(CO)4(μ-sdt)(μ-dppm)] (2) and [Fe2(CO)4(μ-sdt)(μ-dcpm)] (3), respectively. The complex [Fe2(CO)4(μ-sdt)(κ2-dppv)] (4) with a chelating diphosphine was
Introduction : Digital Methods and Experiential Approaches to the Past
In this chapter, the authors introduce the theme of computational/digital methods in the realm of sensory archaeologies. To this purpose, the concept of sensoriality and its relevance for the archaeological discourse is rediscussed. Key concepts such as perception of material culture help us in better defining possible modalities through which archaeologists can benefit from the use of formal meth
Rapid and biased evolution of canalization during adaptive divergence revealed by dominance in gene expression variability during Arctic charr early development
Serious Conflicts with Benign Outcomes? The Electoral Consequences of Conflictual Cabinet Terminations
Conflictual cabinet terminations are seismic events in democracies, but their consequences are understudied. I argue that the electoral impacts of conflictual cabinet terminations depend on voters’ perceptions of them. Terminations following non-policy conflicts are electorally costly. They signal parties’ deteriorating governing competence, which reduces parties’ vote shares. In contrast, termina
Don't air your dirty laundry: Party leadership contests and parliamentary election outcomes
Staging an open contest is a democratic method to choose a party leader, though its electoral consequences remain unclear. I argue that leadership contests are electorally detrimental to governing parties. Competitive contests signal intraparty policy and/or personality conflict to voters, which damages governing parties’ perceived unity as well as competence in the policy-making process. Thus, le
More spotlight, more problems? Westminster parliamentary systems and leadership replacement in large opposition parties
In this article, I argue that Westminster parliamentary systems encourage large opposition parties to replace their leaders between elections. Parliamentary system structures how parties compete over legislative outcomes. In Westminster systems, the government’s dominance in the legislative process promotes an adversarial government–opposition relationship. Subsequently, large opposition parties’
New insight into myocardin regulation and function in smooth muscle cells
Smooth muscle cells (SMCs) are constituents of hollow inner organs. Their contractile function governs essential physiological functions, such as breathing, eating, blood pressure control, urination, and childbirth. Skeletal and cardiac muscle cells are terminally differentiated cell types, but SMCs are highly plastic and change their phenotype in disease. Cues presented by the microenvironment an
Attract voters or appease activists? Opposition parties’ dilemma and party policy change
Why do mainstream opposition parties sometimes fail to adopt policy positions that are attractive to the wider electorate? In this paper, I construct a game-theoretic model between the party leader, the party’s MPs, and the party organization to illustrate how opposition parties’ platform adjustments depend on the party leader’s risk assessment of being deposed and MPs’ re-election incentives. The
One size doesn't fit all: Voter decision criteria heterogeneity and vote choice
Although classic voting studies noted that voters may reach their voting decision on the basis of different criteria most contemporary voting studies assume that one voting model fits all. Building on the limited, but developing literature on the topic, this paper develops and tests models incorporating voter decision criteria heterogeneity. Paying particular attention to the role of voter sophist
The agenda-setting power of the prime minister party in coalition governments
Despite coalition governments being the most widespread form of government, many aspects of coalition politics are still poorly understood. This is especially true for questions relating to the role of the prime minister party within the coalition. Being the prime minister party seems to imply considerable influence, but little evidence actually exists as to the factors shaping the influence of th
Rainfall, baseflow and sea-level impact on river-flooding in a coastal city
Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer
BACKGROUND: Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or
A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients
The risk of breast cancer associated with CHEK2:c.1100delC is 2-threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci
Public attitudes challenge clinical practice on genetic risk disclosure in favour of healthcare-provided direct dissemination to relatives
The Ethics of Outsourcing Information Conflict: Outlining the Responsibilities of Government Funders to their Civil Society Partners
This report investigates the roles and responsibilities governments assume when they collaborate in areas of information conflict. In particular, it assesses the risks to civil society and the private sector when they engage in countering hostile foreign influence operations with funding from governments. What are governments’ options and limitations when supporting civilian populations to counter
Sailing Along the Coast of North Etruria : Ancient Perceptions Versus Multidisciplinary Coastal Landscape Studies
Aim of this contribution is to demonstrate how digital methods, in combination with traditional sources, can effectively contribute to reconstruct a narrative of the past based on a sensory account of a few coastal landscapes in Northwestern Etruria as they were perceived and described by ancient authors. A few passages by Strabo (Geogr. 5.2.5, 222C, Augustan period) and Rutilius Namatianus (de re