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The Interplay of US and International Term Premiums: The Role of Uncertainty and Economic Conditions
We explore the determinants of term premiums and evaluate the influence of the US market on term premiums in seven developed countries. Our analysis shows that poor economic conditions and high uncertainty lead to increased term premiums. Further, our results highlight the importance of US economic conditions and uncertainty factors as well as the supply of US government bonds as key drivers of in
Clinical assessment and treatment of patients presenting with longstanding hip and groin pain in primary care: a survey study among physical therapists and general practitioners in Sweden
Abstract Background Methods of assessment, treatment and referral rates of patients presenting with longstanding hip and groin pain (LHGP) are not well documented. The aim of this study was to investigate assessment and treatment of patients with LHGP among general practitioners (GPs) and physical therapists (PTs) in primary care. Methods An anonymous web-based survey was developed specifically fo
Andean lakes : endangered by natural and anthropogenic threats
The Andes mountains extend north–south in a latitudinal gradient of 8500 km. Because of the great climatic variety and the peculiar north–south orographic distribution, lakes are highly diverse, including different lake origins and contrasting morphometries. We reviewed >700 ecological studies on Andean lakes to identify the main threats to these freshwater systems. The most important threats are
Diastereospecific Synthesis of Vicinally Substituted 2-Oxazolidinones via Oxidative Rearrangement of α,β-Unsaturated γ-Lactams
A diastereospecific synthesis of vicinally substituted 2-oxazolidinones from α,β-unsaturated lactams using m-chloroperoxybenzoic acid is reported. Several highly substituted 2-oxazolidinones were obtained in 19-46% yields in a one-pot reaction with complete control over the relative stereochemistry. The proposed reaction sequence consists of a Baeyer-Villiger oxidation, an epoxidation, and a conce
Sustained Response to Entrectinib in an Infant With a Germline ALKAL2 Variant and Refractory Metastatic Neuroblastoma With Chromosomal 2p Gain and Anaplastic Lymphoma Kinase and Tropomyosin Receptor Kinase Activation
A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues
Recent research on normal human tissues identified omnipresent clones of cells, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumor evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a
Loss of ret promotes mesenchymal identity in neuroblastoma cells
Aberrant activation of anaplastic lymphoma kinase (ALK) drives neuroblastoma (NB). Previous work identified the RET receptor tyrosine kinase (RTK) as a downstream target of ALK activity in NB models. We show here that ALK activation in response to ALKAL2 ligand results in the rapid phosphorylation of RET in NB cells, providing additional insight into the contribution of RET to the ALK-driven gene
Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor which has been implicated in numerous solid and hematologic cancers. ALK mutations are reported in about 5-7% of neuroblastoma cases but the ALK-positive percentage increases significantly in the relapsed patient population. Crizotinib, the first clinically approved ALK inhibitor for the treatment of ALK-positive lung cancer has had le
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma
Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib
Tumors with anaplastic lymphoma kinase (ALK) fusion rearrangements, including non-small-cell lung cancer and anaplastic large cell lymphoma, are highly sensitive to ALK tyrosine kinase inhibitors (TKIs), underscoring the notion that such cancers are addicted to ALK activity. Although mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been dis
Anaplastic lymphoma kinase L1198F and G1201E mutations identified in anaplastic thyroid cancer patients are not ligandindependent
Activating mutations in full length anaplastic lymphoma kinase (ALK) have been reported in neuroblastoma and in anaplastic thyroid cancer. ALK-L1198F and ALKG1201E mutations were originally identified in anaplastic thyroid cancer (ATC) and characterized as constitutively activating mutations. In this study, we employed in vitro cell culture assays together with biochemical and in vivo Drosophila a
BioID-Screening Identifies PEAK1 and SHP2 as Components of the ALK Proximitome in Neuroblastoma Cells
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that is mutated in approximately 10% of pediatric neuroblastoma (NB). To shed light on ALK-driven signaling processes, we employed BioID-based in vivo proximity labeling to identify molecules that interact intracellularly with ALK. NB-derived SK-N-AS and SK-N-BE(2) cells expressing inducible ALK-BirA* fusion proteins were generat
ATR inhibition enables complete tumour regression in ALK-driven NB mouse models
High-risk neuroblastoma (NB) often involves MYCN amplification as well as mutations in ALK. Currently, high-risk NB presents significant clinical challenges, and additional therapeutic options are needed. Oncogenes like MYCN and ALK result in increased replication stress in cancer cells, offering therapeutically exploitable options. We have pursued phosphoproteomic analyses highlighting ATR activi
Public support for climate policies and its ideological predictors across countries of the Global North and Global South
Our understanding of public support for climate policies predominantly stems from studies in the Global North and a focus on isolated policy types. Here, we examine how public support for four different climate policy types and the effect of ideological explanatory variables on such support vary among countries of the Global North and Global South. We surveyed representative samples of each three
Phylogenetic characterization of Bifidobacterium kimbladii sp. nov., a novel species from the honey stomach of the honeybee Apis mellifera
Six novel Bifidobacterium strains H1HS16NT, Bin2N, Hma3N, H6bp22N, H1HS10N, and H6bp9N, were isolated from the honey stomach of Apis mellifera. Cells are Gram-positive, non-motile, non-sporulating, facultatively anaerobic, and fructose 6-phosphate phosphoketolase-positive. Optimal growth conditions occur at 37 °C in anaerobiosis in MRS medium added with 2 % fructose and 0.1 % L-cysteine. The 16S r
Becoming intimate with algorithms : towards a critical antagonism via algorithmic art
This article takes departure in the notion of intimacy to identify the critical dependencies with contemporary algorithms. The presented concept of algorithmic intimacies points to how contemporary life is premised on the co-habitation with algorithms which poses various challenges to tactical approaches against algorithmic forms of governance. The article argues that thinking through these algori
Synthetic Data : Servicing Privacy
In contemporary society, big tech platforms have leveraged their ownership over global data infrastructures and have established powerful influence over the conditions of digitally mediated life. The ubiquity of platform-mediated information technology has engendered a growing sense of unease about surveillance and loss of personal autonomy. This awareness has motivated repeated calls for expandin
Beyond Privacy : People, Practices, Politics
Discussions around digital technologies, new media, platforms and information have long centred on the protection of personal data and privacy. This timely volume extends the conversation to address fundamental societal and structural issues from three perspectives: people, practices and politics. Organised around an international collection of case studies, the book provides a valuable contributi