Extreme geomagnetic field variability indicated by Eastern Mediterranean full-vector archaeomagnetic records

The magnetic field of the Earth can exhibit considerable variations at short time scales, even as short as decades. The archaeomagnetic studies of Middle Eastern artefacts (mainly from Israel and Jordan) show evidence for an exceptionally high intensity period from 1050-700 BC which displays two distinct spikes over the Levant, the Levantine Iron Age Anomaly (LIAA). Its exact duration and geographical extent are still poorly known. Despite the wealth of ancient settlements, the extensive cultural heritage and a long history of trade and immigration, the archaeomagnetism of Turkey and Cyprus remains largely unexplored. This study presents a large data set of ancient directions and intensities from seven archaeological sites in the Eastern Mediterranean covering a time span of ∼2000 yrs. The recorded directions from thirteen sets of samples are coherent with our earlier findings, yet show significantly larger swings than existing field models. In particular, we confirm the very large swing in inclination we found earlier, from 1910-1850 BC, that is also captured by the Greek PSV curve, and shallower by more than 10° than predicted by existing field models. Consequently, these models require substantial revision in this region. We were able to determine the archaeointensity from five sets of mud-bricks, from the thirteen attempted, allowing us to provide the full field vector. Furthermore, we present thirty-one new archaeointensity results from potsherds and mud-bricks that considerably enhance existing data, especially when a set of strict selection criteria is applied. Fourteen sets of potsherds from a single site (Tell Atchana) provide the longest sequence recorded so far in Turkey, from 2100 to 1350 BC. We find exceptionally high intensities of 145 and 175 ZAm2 around 700 BC, in well-dated mud-bricks and potsherds from two different locations (Tell Tayinat and Kilise Tepe), supporting extreme geomagnetic field variability in the region. Moreover, these two high intensities confirm the younger spike of the LIAA in Turkey

Multiway modeling and analysis in stem cell systems biology

<p>Abstract</p> <p>Background</p> <p>Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.). A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models) can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells.</p> <p>Results</p> <p>We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC) models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a collagen I substrate accelerated the osteogenic differentiation induced by a static collagen I substrate.</p> <p>Conclusion</p> <p>Our results suggest gene- and protein-level models whereby stem cells undergo transdifferentiation to osteoblasts, and lay the foundation for mechanistic, hypothesis-driven studies. Our analysis methods are applicable to a wide range of stem cell differentiation models.</p

Deficient Signaling via Alk2 (Acvr1) Leads to Bicuspid Aortic Valve Development

Bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly in humans. Despite recent advances, the molecular basis of BAV development is poorly understood. Previously it has been shown that mutations in the Notch1 gene lead to BAV and valve calcification both in human and mice, and mice deficient in Gata5 or its downstream target Nos3 have been shown to display BAVs. Here we show that tissue-specific deletion of the gene encoding Activin Receptor Type I (Alk2 or Acvr1) in the cushion mesenchyme results in formation of aortic valve defects including BAV. These defects are largely due to a failure of normal development of the embryonic aortic valve leaflet precursor cushions in the outflow tract resulting in either a fused right- and non-coronary leaflet, or the presence of only a very small, rudimentary non-coronary leaflet. The surviving adult mutant mice display aortic stenosis with high frequency and occasional aortic valve insufficiency. The thickened aortic valve leaflets in such animals do not show changes in Bmp signaling activity, while Map kinase pathways are activated. Although dysfunction correlated with some pro-osteogenic differences in gene expression, neither calcification nor inflammation were detected in aortic valves of Alk2 mutants with stenosis. We conclude that signaling via Alk2 is required for appropriate aortic valve development in utero, and that defects in this process lead to indirect secondary complications later in life

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Shedding light on the past

The Amuq valley or plain of Antioch, located in the Hatay province of south central Turkey, has been densely inhabited by humans for some 9,000 years. The plain provides a fruitful ground for archaeological study due to the abnormally large number of preserved ancient sites found there. Surrounded by mountains on all sides and fed by three rivers, the fertile valley provides an opportunity to study the relationship of ancient man and his environment in microcosm. The floor of the valley has been the home of several lakes: some of the largest archaeological sites existing in the mid-late Holocene appear to have been located near-by the Lake of Antioch which evolved during this period. A sedimentary core, representing an estimated 7,000 years of history, was taken from the lake. Synchrotron x-ray fluorescence measurements were performed on sections of the core. Analysis yielded the distribution of elemental masses spanning from Ca to Mo as a function of depth from the surface. Figure 1 shows the results for Cu. Changes in elemental concentration with time reflect the changes in the local environment at the time of deposition. Higher concentrations of copper may reflect metal working activities: there is a maximum in Fig. 1 around 5000 BP, a high period in settlement history. Elemental concentrations measured follow a number of distinct patterns that may be related to local geomorphology and climate. In this fashion a historical account of the development of the Lake of Antioch was constructed from the data. The ebb and swell of the lake as well as changes in the local river courses directly influence man’s presence in the region. Signals of such environmental change can be discerned from tracking diachronic changes in elemental concentrations throughout the sediment core. These elements serve as proxies for environmental change, both human and climate induced. The data suggest that man’s activities may have aggravated some of the erosional processes. © ANST