Three-dimensional magnetic flux rope structure formed by multiple sequential X-line reconnection at the magnetopause

On 14 June 2007, four Time History of Events and Macroscale Interactions during Substorms spacecraft observed a flux transfer event (FTE) on the dayside magnetopause, which has been previously proved to be generated by multiple, sequential X-line reconnection (MSXR) in a 2-D context. This paper reports a further study of the MSXR event to show the 3-D viewpoint based on additional measurements. The 3-D structure of the FTE flux rope across the magnetospheric boundary is obtained on the basis of multipoint measurements taken on both sides of the magnetopause. The flux rope's azimuthally extended section is found to lie approximately on the magnetopause surface and parallel to the X-line direction; while the axis of the magnetospheric branch is essentially along the local unperturbed magnetospheric field lines. In the central region of the flux rope, as distinct from the traditional viewpoint, we find from the electron distributions that two types of magnetic field topology coexist: opened magnetic field lines connecting the magnetosphere and the magnetosheath and closed field lines connecting the Southern and Northern hemispheres. We confirm, therefore, for the first time, the characteristic feature of the 3-D reconnected magnetic flux rope, formed through MSXR, through a determination of the field topology and the plasma distributions within the flux rope. Knowledge of the complex geometry of FTE flux ropes will improve our understanding of solar wind-magnetosphere interaction.Astronomy & AstrophysicsSCI(E)5ARTICLE51904-191111

Extended magnetic reconnection across the dayside magnetopause

The extent of where magnetic reconnection (MR), the dominant process responsible for energy and plasma transport into the magnetosphere, operates across Earth’s dayside magnetopause has previously been only indirectly shown by observations. We report the first direct evidence of X-line structure resulting from the operation of MR at each of two widely separated locations along the tilted, subsolar line of maximum current on Earth’s magnetopause, confirming the operation of MR at two or more sites across the extended region where MR is expected to occur. The evidence results from in-situ observations of the associated ion and electron plasma distributions, present within each magnetic X-line structure, taken by two spacecraft passing through the active MR regions simultaneously

Hypoxia promotes breast cancer cell invasion through HIF-1a-mediated up-regulation of the invadopodial actin bundling protein CSRP2

Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumour specimens. We functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. Remarkably, CSRP2 knockdown significantly inhibits hypoxia-stimulated invadopodium formation, ECM degradation and invasion in MDA-MB-231 cells, while CSRP2 forced expression was sufficient to enhance the invasive capacity of HIF-1a-depleted cells under hypoxia. In MCF-7 cells, CSRP2 upregulation was required for hypoxia-induced formation of invadopodium precursors that were unable to promote ECM degradation. Collectively, our data support that CSRP2 is a novel and direct cytoskeletal target of HIF-1 which facilitates hypoxia-induced breast cancer cell invasion by promoting invadopodia formation.The authors are grateful to Monika Dieterle, Arnaud Muller, Pter Nazarov and Muhammad Zaeem Noman (Oncology Department, LIH, Luxembourg) for technical assistance, support in statistical analyses and constructive discussions. The authors also warmly thank Sara A. Courtneidge for the gift of the Tks5-GFP construct (Oregon Health and Science University, Portland, USA). This work was mainly supported by a research grant from “Fondation Cancer” Luxembourg (FC/2016/02), and the National Research Fund (C16/ BM/11297905). Joshua Brown Clay is recipient of a Postdoctoral fellowship from “Fonds De La Recherche Scientifque” - FNRS “Télévie” (7.4512.16). Antoun Al Absi and Hannah Wurzer are recipients of PhD fellowships from the National Research Fund, Luxembourg (AFR7892325 and PRIDE15/10675146/CANBIO, respectively)

Evidence for a flux transfer event generated by multiple X-line reconnection at the magnetopause

Magnetic flux transfer events (FTEs) are signatures of unsteady magnetic reconnection, often observed at planetary magnetopauses. Their generation mechanism, a key ingredient determining how they regulate the transfer of solar wind energy into magnetospheres, is still largely unknown. We report THEMIS spacecraft observations on 2007-06-14 of an FTE generated by multiple X-line reconnection at the dayside magnetopause. The evidence consists of (1) two oppositely-directed ion jets converging toward the FTE that was slowly moving southward, (2) the cross-section of the FTE core being elongated along the magnetopause normal, probably squeezed by the oppositely-directed jets, and (3) bidirectional field-aligned fluxes of energetic electrons in the magnetosheath, indicating reconnection on both sides of the FTE. The observations agree well with a global magnetohydrodynamic model of the FTE generation under large geomagnetic dipole tilt, which implies the efficiency of magnetic flux transport into the magnetotail being lower for larger dipole tilt

Cluster and MMS simultaneous observations of magnetosheath high speed jets and their impact on the magnetopause

When the supersonic solar wind encounters the Earth's magnetosphere a shock, called bow shock, is formed and the plasma is decelerated and thermalized in the magnetosheath downstream from the shock. Sometimes, however, due to discontinuities in the solar wind, bow shock ripples or ionized dust clouds carried by the solar wind, high speed jets (HSJs) are observed in the magnetosheath. These HSJs have typically a Vx component larger than 200 km s−1 and their dynamic pressure can be a few times the solar wind dynamic pressure. They are typically observed downstream from the quasi-parallel bow shock and have a typical size around one Earth radius (RE) in XGSE. We use a conjunction of Cluster and MMS, crossing simultaneously the magnetopause, to study the characteristics of these HSJs and their impact on the magnetopause. Over 1 h 15 min interval in the magnetosheath, Cluster observed 21 HSJs. During the same period, MMS observed 12 HSJs and entered the magnetosphere several times. A jet was observed simultaneously by both MMS and Cluster and it is very likely that they were two distinct HSJs. This shows that HSJs are not localized into small regions but could span a region larger than 10 RE, especially when the quasi-parallel shock is covering the entire dayside magnetosphere under radial IMF. During this period, two and six magnetopause crossings were observed, respectively, on Cluster and MMS with a significant angle between the observation and the expected normal deduced from models. The angles observed range between from 11° up to 114°. One inbound magnetopause crossing observed by Cluster (magnetopause moving out at 142 km s−1) was observed simultaneous to an outbound magnetopause crossing observed by MMS (magnetopause moving in at −83 km s−1), showing that the magnetopause can have multiple local indentation places, most likely independent from each other. Under the continuous impacts of HSJs, the magnetopause is deformed significantly and can even move in opposite directions at different places. It can therefore not be considered as a smooth surface anymore but more as surface full of local indents. Four dust impacts were observed on MMS, although not at the time when HSJs are observed, showing that dust clouds would have been present during the observations. No dust cloud in the form of Interplanetary Field Enhancements was however observed in the solar wind which may exclude large clouds of dust as a cause of HSJs. Radial IMF and Alfvén Mach number above 10 would fulfill the criteria for the creation of bow shock ripples and the subsequent crossing of HSJs in the magnetosheath.publishedVersio

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients’ survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.publishedVersio

Exact Vlasov-Maxwell equilibria for asymmetric current sheets

The NASA Magnetospheric Multiscale mission has made in situ diffusion region and kinetic-scale resolution measurements of asymmetric magnetic reconnection for the first time, in the Earth's magnetopause. The principal theoretical tool currently used to model collisionless asymmetric reconnection is particle-in-cell simulations. Many particle-in-cell simulations of asymmetric collisionless reconnection start from an asymmetric Harris-type magnetic field but with distribution functions that are not exact equilibrium solutions of the Vlasov equation. We present new and exact equilibrium solutions of the Vlasov-Maxwell system that are self-consistent with one-dimensional asymmetric current sheets, with an asymmetric Harris-type magnetic field profile, plus a constant nonzero guide field. The distribution functions can be represented as a combination of four shifted Maxwellian distribution functions. This equilibrium describes a magnetic field configuration with more freedom than the previously known exact solution and has different bulk flow properties

Wind anisotropies and GRB progenitors

We study the effect of wind anisotropies on the stellar evolution leading to collapsars. Rotating models of a 60 M$_\odot$ star with $\Omega/\Omega_{\rm crit}=0.75$ on the ZAMS, accounting for shellular rotation and a magnetic field, with and without wind anisotropies, are computed at $Z$=0.002 until the end of the core He-burning phase. Only the models accounting for the effects of the wind anisotropies retain enough angular momentum in their core to produce a Gamma Ray Burst (GRB). The chemical composition is such that a type Ic supernova event occurs. Wind anisotropies appear to be a key physical ingredient in the scenario leading to long GRBs.Comment: 5 pages, 4 figures, accepted for publication in A&A Lette

Serine Protease PRSS23 Is Upregulated by Estrogen Receptor α and Associated with Proliferation of Breast Cancer Cells

Serine protease PRSS23 is a newly discovered protein that has been associated with tumor progression in various types of cancers. Interestingly, PRSS23 is coexpressed with estrogen receptor α (ERα), which is a prominent biomarker and therapeutic target for human breast cancer. Estrogen signaling through ERα is also known to affect cell proliferation, apoptosis, and survival, which promotes tumorigenesis by regulating the production of numerous downstream effector proteins

A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy

We investigated the mRNA expression levels of all six antiapoptotic Bcl-2 subfamily members in 68 human cancer cell lines using qPCR techniques and measured the ability of known Bcl-2 inhibitors to induce cell death in 36 of the studied tumor cell lines. Our study reveals that Mcl-1 represents the anti-apoptotic Bcl-2 subfamily member with the highest mRNA levels in the lung, prostate, breast, ovarian, renal, and glioma cancer cell lines. In leukemia/lymphoma and melanoma cancer cell lines, Bcl-2 and Bfl-1 had the highest levels of mRNA, respectively. The observed correlation between the cell killing properties of known Bcl-2 inhibitors and the relative mRNA expression levels of anti-apoptotic Bcl-2 proteins provide critical insights into apoptosis-based anticancer strategies that target Bcl-2 proteins. Our data may explain current challenges of selective Bcl-2 inhibitors in the clinic, given that severe expression of Bcl-2 seems to be limited to leukemia cell lines. Furthermore, our data suggest that in most cancer types a strategy targeted to Mcl-1 inhibition, or combination of Bfl-1 and Mcl-1 inhibition for melanoma, may prove to be more successful than therapies targeting only Bcl-2