Investigating long-term human ecodynamics in the European Arctic:Towards an integrated multi-scalar analysis of early and mid Holocene cultural, environmental and palaeodemographic sequences in Finnmark County, Northern Norway

Most parts of the Circumpolar Arctic have only discontinuous evidence for long-term human settlement. In contrast, Northern Norway has an unbroken archaeological record that extends back to the early Holocene. Numerous high-resolution archaeological and palaeoenvironmental records have been generated by commercial excavations and surveys, offering archaeologists unique opportunities to investigate long-term human ecodynamics in an Arctic coastal setting. To date, however, deeper analysis of the new datasets has yet to be undertaken. This paper aims to present a new synthesis of early and mid Holocene archaeological and paleoenvironmental sequences for Western Finnmark (11500-2000 cal BP). This enables us to identify three major phases of culture change that broadly correlate with climatic and environmental shifts. We then present emerging results from our multi-scalar analysis of the processes driving these transformations. At supra-regional and regional scales, our palaeodemographic modelling indicates major population events centered around 6000 cal BP and 4000 cal BP. At intra-regional scales, we are identifying spatial clustering of prehistoric settlements into local socio-economic communities. At the scale of local settlements, our analysis of house-pit chronologies is clarifying the degree of simultaneous occupation and re-use. We also draw on recent research into rock art and ritual landscapes in an effort to reconstruct the relationship between settlement clusters and general interaction patterns. Integration of these diverse lines of evidence is generating a vivid picture of thriving Arctic coastal communities, with indications that the timing and pace of cultural responses to climatic and environmental changes were more complex than previously thought

Copynumber: Efficient algorithms for single- and multi-track copy number segmentation.

BACKGROUND: Cancer progression is associated with genomic instability and an accumulation of gains and losses of DNA. The growing variety of tools for measuring genomic copy numbers, including various types of array-CGH, SNP arrays and high-throughput sequencing, calls for a coherent framework offering unified and consistent handling of single- and multi-track segmentation problems. In addition, there is a demand for highly computationally efficient segmentation algorithms, due to the emergence of very high density scans of copy number. RESULTS: A comprehensive Bioconductor package for copy number analysis is presented. The package offers a unified framework for single sample, multi-sample and multi-track segmentation and is based on statistically sound penalized least squares principles. Conditional on the number of breakpoints, the estimates are optimal in the least squares sense. A novel and computationally highly efficient algorithm is proposed that utilizes vector-based operations in R. Three case studies are presented. CONCLUSIONS: The R package copynumber is a software suite for segmentation of single- and multi-track copy number data using algorithms based on coherent least squares principles.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. Results: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.Peer reviewe

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice

Recurrent PTPRB and PLCG1 mutations in angiosarcoma

Angiosarcoma is an aggressive malignancy that arises spontaneously or secondarily to ionizing radiation or chronic lymphoedema. Previous work has identified aberrant angiogenesis, including occasional somatic mutations in angiogenesis signaling genes, as a key driver of angiosarcoma. Here we employed whole-genome, whole-exome and targeted sequencing to study the somatic changes underpinning primary and secondary angiosarcoma. We identified recurrent mutations in two genes, PTPRB and PLCG1, which are intimately linked to angiogenesis. The endothelial phosphatase PTPRB, a negative regulator of vascular growth factor tyrosine kinases, harbored predominantly truncating mutations in 10 of 39 tumors (26%). PLCG1, a signal transducer of tyrosine kinases, encoded a recurrent, likely activating p.Arg707Gln missense variant in 3 of 34 cases (9%). Overall, 15 of 39 tumors (38%) harbored at least one driver mutation in angiogenesis signaling genes. Our findings inform and reinforce current therapeutic efforts to target angiogenesis signaling in angiosarcoma

Democracy and cooperation in commons management: Experimental evidence of representative and direct democracy from community forests in Ethiopia

Abstract The authors use dynamic lab-in-the-field common pool resource experiments to investigate the role of two forms of democracy on the cooperation of forest users in Ethiopia. In this experimental setup, participants can either directly select a rule (direct democracy) or elect a leader who decides on the introduction of rules (representative democracy). These two treatments are compared with the imposition of rules and imposition of leaders. It is found that both endogenous leaders elected by the community members and endogenous rules selected by the direct involvement of the participants are more effective in promoting cooperation among the community members compared to exogenous leadership, exogenous rule imposition and the baseline scenario without any of these modifications. However, no significant difference is found between representative democracy in the election of leadership and direct democracy in the selection of rules. Leadership characteristics and behavior are further analyzed. The results underline the importance of democratic procedures