Multi-scale three-dimensional characterization of iron particles in dusty olivine: Implications for paleomagnetism of chondritic meteorites

Dusty olivine (olivine containing multiple sub-micrometer inclusions of metallic iron) in chondritic meteorites is considered an ideal carrier of paleomagnetic remanence, capable of maintaining a faithful record of pre-accretionary magnetization acquired during chondrule formation. Here we show how the magnetic architecture of a single dusty olivine grain from the Semarkona LL3.0 ordinary chondrite meteorite can be fully characterised in three dimensions, using a combination of Focussed-Ion-Beam nanotomography (FIB-nT), electron tomography and finite-element micromagnetic modelling. We present a three-dimensional (3D) volume reconstruction of a dusty olivine grain, obtained by selective milling through a region of interest in a series of sequential 20 nm slices, which are then imaged using scanning electron microscopy. The data provide a quantitative description of the iron particle ensemble, including the distribution of particle sizes, shapes, interparticle spacings and orientations. Iron particles are predominantly oblate ellipsoids with average radii 242 ± 94 nm by 199 ± 80 nm by 123 ± 58 nm. Using analytical TEM we observe that the particles nucleate on sub-grain boundaries and are loosely arranged in a series of sheets parallel to (001) of the olivine host. This is in agreement with the orientation data collected using the FIB-nT, and highlights how the underlying texture of the dusty olivine is crystallographically constrained by the olivine host. The shortest dimension of the particles is oriented normal to the sheets and their longest dimension is preferentially aligned within the sheets. Individual particle geometries are converted to a finite-element mesh and used to perform micromagnetic simulations. The majority of particles adopt a single vortex state, with ‘bulk’ spins that rotate around a central vortex core. We observed no particles, which are in a true single domain state. The results of the micromagnetic simulations challenge some pre-conceived ideas about the remanence carrying properties of vortex states. There is often not a simple predictive relationship between the major, intermediate and minor axes of the particles and the remanence vector imparted in different fields. Although the orientation of the vortex core is determined largely by the ellipsoidal geometry (i.e., parallel to the major axis for prolate ellipsoids and parallel to the minor axis for oblate ellipsoids), the core and remanence vectors can sometimes lie at very large (tens of degree) angles to the principal axes. The subtle details of the morphology can control the overall remanence state, leading in some cases to a dominant contribution from the bulk spins to the net remanence, with profound implications for predicting the anisotropy of the sample. The particles have very high switching fields (several hundred mT), demonstrating their high stability and suitability for paleointensity studies.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC grant agreements 291522-3DIMAGE (P.A.M.) and 320750 - Nanopaleomagnetism (J.F.E., R.J.H., and P.A.M.). BPW and RRF were supported by NASA Emerging Worlds program grant #NNX15AH72G, the NASA Solar System Exploration and Research Virtual Institute grant #NNA14AB01A, and a generous gift from Thomas F. Peterson, Jr. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 320832-Imagine. (W.W . and P.O.C.) W.W. was also supported for this research under NERC grant NE/J020966/1 - Predicting the reliability with which the geomagnetic field can be recorded in igneous rocks.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Mineralogical Society of America

The effect of glucocorticoids on tendon cell viability in human tendon explants

Background and purpose Previous studies on the culture of human tenocytes have shown that dexamethasone and triamcino-lone reduce cell viability, suppress cell proliferation, and reduce collagen synthesis. However, such cell cultures lack the extracellular matrix and three-dimensional structure of normal tendons, which affects their response to stimuli. We established a human tendon explant culture system and tested the effects of dexamethasone and triamcinolone on cell viability

A Time-Resolved Paleomagnetic Record of Main Group Pallasites: Evidence for a Large-Cored, Thin-Mantled Parent Body

Funder: FP7 Ideas: European Research Council (FP7 Ideas); Id: http://dx.doi.org/10.13039/100011199; Grant(s): 320750, 312284Funder: NASA Solar Systems Workings programFunder: The Geological SocietyFunder: Mineralogical Society of Great BritainFunder: Mineral Physics Group of Great BritainFunder: Jesus College CambridgeFunder: Royal Astronomical Society; Id: http://dx.doi.org/10.13039/501100000698Abstract: Several paleomagnetic studies have been conducted on five Main Group pallasites: Brenham, Marjalahti, Springwater, Imilac, and Esquel. These pallasites have distinct cooling histories, meaning that their paleomagnetic records may have been acquired at different times during the thermal evolution of their parent body. Here, we compile new and existing data to present the most complete time‐resolved paleomagnetic record for a planetesimal, which includes a period of quiescence prior to core solidification as well as dynamo activity generated by compositional convection during core solidification. We present new paleomagnetic data for the Springwater pallasite, which constrains the timing of core solidification. Our results suggest that in order to generate the observed strong paleointensities (∼65–95 μT), the pallasites must have been relatively close to the dynamo source. Our thermal and dynamo models predict that the Main Group pallasites originate from a planetesimal with a large core (>200 km) and a thin mantle (<70 km)

An outcome analysis of self-expandable metallic stents in central airway obstruction: a cohort study

<p>Abstract</p> <p>Background</p> <p>Self-expandable metallic stents (SEMSs) have provided satisfactory management of central airway obstruction. However, the long-term benefits and complications of this management modality in patients with benign and malignant obstructing lesions after SEMS placement are unclear. We performed this cohort study to analyze the outcomes of Ultraflex SEMSs in patients with tracheobronchial diseases.</p> <p>Methods</p> <p>Of 149 patients, 72 with benign and 77 with malignant tracheobronchial disease received 211 SEMSs (benign, 116; malignant, 95) and were retrospectively reviewed in a tertiary hospital.</p> <p>Results</p> <p>The baseline characteristics of patients who received SEMS implantation for benign conditions and those who underwent implantation for malignant conditions were significantly different. These characteristics included age (mean, 63.9 vs. 58; <it>p </it>< 0.01), gender (male, 62% vs. 90%; <it>p </it>< 0.0001), smoking (47% vs. 85%; <it>p </it>< 0.0001), forced expiratory volume in 1 second (mean, 0.9 vs. 1.47 L/s; <it>p </it>< 0.0001), follow-up days after SEMS implantation (median; 429 vs. 57; <it>p </it>< 0.0001), and use of covered SEMS (36.2% vs. 94.7%; <it>p </it>< 0.0001). Symptoms improved more after SEMS implantation in patients with benign conditions than in those with malignant conditions (76.7% vs. 51.6%; <it>p </it>< 0.0001). The overall complication rate after SEMS implantation in patients with benign conditions was higher than that in patients with malignancy (42.2% vs. 21.1%; <it>p </it>= 0.001). Successful management of SEMS migration, granulation tissue formation, and SEMS fracture occurred in 100%, 81.25%, and 85% of patients, respectively.</p> <p>Conclusions</p> <p>Patients who received SEMS implantation owing to benign conditions had worse lung function and were older than those who received SEMS for malignancies. There was higher complication rate in patients with benign conditions after a longer follow-up period owing to the nature of the underlying diseases.</p

Long-lived magnetism from solidification-driven convection on the pallasite parent body.

Palaeomagnetic measurements of meteorites suggest that, shortly after the birth of the Solar System, the molten metallic cores of many small planetary bodies convected vigorously and were capable of generating magnetic fields. Convection on these bodies is currently thought to have been thermally driven, implying that magnetic activity would have been short-lived. Here we report a time-series palaeomagnetic record derived from nanomagnetic imaging of the Imilac and Esquel pallasite meteorites, a group of meteorites consisting of centimetre-sized metallic and silicate phases. We find a history of long-lived magnetic activity on the pallasite parent body, capturing the decay and eventual shutdown of the magnetic field as core solidification completed. We demonstrate that magnetic activity driven by progressive solidification of an inner core is consistent with our measured magnetic field characteristics and cooling rates. Solidification-driven convection was probably common among small body cores, and, in contrast to thermally driven convection, will have led to a relatively late (hundreds of millions of years after accretion), long-lasting, intense and widespread epoch of magnetic activity among these bodies in the early Solar System.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement No. 320750, the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312284, the Natural Environment Research Council, Fundación ARAID and the Spanish MINECO MAT2011-23791.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/nature/journal/v517/n7535/full/nature14114.html

Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability

Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS

Eph/Ephrin Profiling in Human Breast Cancer Reveals Significant Associations between Expression Level and Clinical Outcome

Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment

Single Tube, High Throughput Cloning of Inverted Repeat Constructs for Double-Stranded RNA Expression

BACKGROUND: RNA interference (RNAi) has emerged as a powerful tool for the targeted knockout of genes for functional genomics, system biology studies and drug discovery applications. To meet the requirements for high throughput screening in plants we have developed a new method for the rapid assembly of inverted repeat-containing constructs for the in vivo production of dsRNAs. METHODOLOGY/PRINCIPAL FINDINGS: The procedure that we describe is based on tagging the sense and antisense fragments with unique single-stranded (ss) tails which are then assembled in a single tube Ligase Independent Cloning (LIC) reaction. Since the assembly reaction is based on the annealing of unique complementary single stranded tails which can only assemble in one orientation, greater than ninety percent of the resultant clones contain the desired insert. CONCLUSION/SIGNIFICANCE: Our single-tube reaction provides a highly efficient method for the assembly of inverted repeat constructs for gene suppression applications. The single tube assembly is directional, highly efficient and readily adapted for high throughput applications

CRISPR transcriptional repression devices and layered circuits in mammalian cells

A key obstacle to creating sophisticated genetic circuits has been the lack of scalable device libraries. Here we present a modular transcriptional repression architecture based on clustered regularly interspaced palindromic repeats (CRISPR) system and examine approaches for regulated expression of guide RNAs in human cells. Subsequently we demonstrate that CRISPR regulatory devices can be layered to create functional cascaded circuits, which provide a valuable toolbox for engineering purposes.National Institutes of Health (U.S.) (Grant 5R01CA155320-04)National Institutes of Health (U.S.) (Grant P50 GM098792)Korea (South). Ministry of Science, Information and Communication Technolgy. Intelligent Synthetic Biology Center of Global Frontier Project (2013M3A6A8073557

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family