The alpine Swiss-French airborne gravity survey

In February 1998, a regional-scale, airborne gravity survey was carried out over the French Occidental Alps within the framework of the GéoFrance 3-D research program.The survey consisted of 18 NS and 16 EW oriented lines with a spacing of 10 and 20 km respectively, covering the whole of the Western French Alps (total area: 50 000 km2; total distance of lines flown: 10 000 km). The equipment was mounted in a medium-size aircraft (DeHavilland Twin Otter) flowing at a constant altitude of 5100 m a.s.l, and at a mean ground speed of about 280 km h−1. Gravity was measured using a LaCoste & Romberg relative, air/sea gravimeter (type SA) mounted on a laser gyro stabilized platform. Data from 5 GPS antennae located on fuselage and wings and 7 ground-based GPS reference stations were used to determine position and aircraft induced accelerations.The gravimeter passband was derived by comparing the vertical accelerations provided by the gravimeter with those estimated from the GPS positions. This comparison showed that the gravimeter is not sensitive to very short wavelength aircraft accelerations, and therefore a simplified formulation for computing airborne gravity measurements was developed. The intermediate and short wavelength, non-gravitational accelerations were eliminated by means of digital, exponential low-pass filters (cut-off wavelength: 16 km). An important issue in airborne gravimetry is the reliability of the airborne gravity surveys when compared to ground surveys. In our studied area, the differences between the airborne-acquired Bouguer anomaly and the ground upward-continued Bouguer anomaly of the Alps shows a good agreement: the rms of these differences is equal to 7.68 mGal for a spatial resolution of 8 km. However, in some areas with rugged topography, the amplitudes of those differences have a striking correlation with the topography. We then argue that the choice of an appropriate density (reduction by a factor of 10 per cent) for computing the ground topographic corrections over the highest mountains, results in significantly reducing the differences between airborne and ground upward-continued Bouguer anomalies, which shows that some of the misfit stems from errors in the ground dat

The Marine Nature of Nuwuk Lake and Small Ponds of the Peninsula of Point Barrow Alaska

Discusses a score or more ponds, some transient, some persistent, on this narrow gravel spit, their location, nature, salinity and temperature; their biotas, marine and fresh-water, are outlined. Nuwuk Lake, the largest water body of the locality, approx. 600 ft long, max. depth 18.5 ft, is treated in some detail: its bottom, its formation by converging currents of the Bering and Chukchi Seas, ice conditions, temperature, salinity and O2-content. The biotas: euryhaline, reduced shallow-sea fauna are dealt with and the organisms collected during 1952-1960 are tabulated. Comparison is made with the few halocline lakes known in northern Russia and Scandinavia, notably Mogil'noye on Kil'din Island

Review of graph-based hazardous event detection methods for autonomous driving systems

Automated and autonomous vehicles are often required to operate in complex road environments with potential hazards that may lead to hazardous events causing injury or even death. Therefore, a reliable autonomous hazardous event detection system is a key enabler for highly autonomous vehicles (e.g., Level 4 and 5 autonomous vehicles) to operate without human supervision for significant periods of time. One promising solution to the problem is the use of graph-based methods that are powerful tools for relational reasoning. Using graphs to organise heterogeneous knowledge about the operational environment, link scene entities (e.g., road users, static objects, traffic rules) and describe how they affect each other. Due to a growing interest and opportunity presented by graph-based methods for autonomous hazardous event detection, this paper provides a comprehensive review of the state-of-the-art graph-based methods that we categorise as rule-based, probabilistic, and machine learning-driven. Additionally, we present an in-depth overview of the available datasets to facilitate hazardous event training and evaluation metrics to assess model performance. In doing so, we aim to provide a thorough overview and insight into the key research opportunities and open challenges

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk

Preclinical Demonstration of Lentiviral Vector-mediated Correction of Immunological and Metabolic Abnormalities in Models of Adenosine Deaminase Deficiency

Gene transfer into autologous hematopoietic stem cells by γ-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA)–deficient severe combined immunodeficiency (SCID). However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy (GT), we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA). In ADA−/− mice, LV EFS ADA displayed high-efficiency gene transfer and sufficient ADA expression to rescue ADA−/− mice from their lethal phenotype with good thymic and peripheral T- and B-cell reconstitution. Human ADA-deficient CD34+ cells transduced with 1–5 × 107 TU/ml had 1–3 vector copies/cell and expressed 1–2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV EFS ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV EFS ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, while reducing the potential for vector-mediated insertional mutagenesis

Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling

Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria use lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection. Here, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, which extend beyond its role as an adhesion molecule. We found that LecB associates with insulin-like growth factor-1 receptor and dampens its signalling, leading to the arrest of cell cycle. In addition, we describe a novel LecB-triggered mechanism to down-regulate host cell receptors by showing that LecB leads to insulin-like growth factor-1 receptor internalisation and subsequent missorting towards intracellular endosomal compartments, without receptor activation. Overall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival

Force transmission in migrating cells

Analysis of the relationship between actin network velocity and traction forces at the substrate shows that force transmission mechanisms vary with distinct regions of the cell

Human brain slices for epilepsy research:pitfalls, solutions and future challenges

Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits

Encapsulation of flavonoid in multiple emulsion using spinning disc reactor technology

Rutin (quercetin-3-rutinoside) and anthocyanin flavonoids have numerous biological activities which are beneficial to human health such as antioxidant and anti-inflammatory effects. In order to aid delivery of their health benefits, an attempt has been made to encapsulate rutin and Hibiscus anthocyanins in multiple emulsions using a spinning disc reactor (SDR) as a novel processing aid. The encapsulation of flavonoids may prolong their shelf-life and increase their bioavailability for absorption by the body (Munin & Edwards-Lévy, 2011). The advantage of using SDR technology in the second stage of emulsification is that it does not break the droplets of the primary emulsion. The time-dependent stability of the multiple emulsions was investigated using particle size, microscopy, visual assessment and stability index measurements. At 2 wt. % emulsifier, Brij 78 was found to be capable of producing uniform droplets of the final W/O/W emulsion in the size range of 13-15 µm. The results show that the SDR technology can be used as an alternative process for making stable W/O/W multiple emulsions with a fairly narrow droplet size distribution. Rutin and anthocyanins were successfully encapsulated within the internal aqueous phase of W/O/W multiple emulsions, giving an encapsulation efficiency of >80%. In the presence of flavonoids, a reduction in the average particle size has also been observed, possibly due to its surface active properties. Confocal laser microscopy confirmed the successful formation of SDR-processed multiple emulsions