Deregulation of the CEACAM Expression Pattern Causes Undifferentiated Cell Growth in Human Lung Adenocarcinoma Cells

CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs) of the carcinoembryonic antigen (CEA) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients. Taken together, our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L, but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation

Predicting Driver Safety in Parkinson’s Disease: An Interim Report of an Ongoing Longitudinal Study

This article summarizes the baseline results of an ongoing longitudinal, NIH-funded study on prediction of driver safety in patients with Parkinson’s disease (PD). Patients with even mild to moderate PD who drive and live independently suffer from visual and cognitive dysfunction, which appear to be the main contributors to decreased driving performance and safety, rather than the motor dysfunction for which PD is known

Structure of the Current Sheet in the 11 July 2017 Electron Diffusion Region Event.

The structure of the current sheet along the Magnetospheric Multiscale (MMS) orbit is examined during the 11 July 2017 Electron Diffusion Region (EDR) event. The location of MMS relative to the X-line is deduced and used to obtain the spatial changes in the electron parameters. The electron velocity gradient values are used to estimate the reconnection electric field sustained by nongyrotropic pressure. It is shown that the observations are consistent with theoretical expectations for an inner EDR in 2-D reconnection. That is, the magnetic field gradient scale, where the electric field due to electron nongyrotropic pressure dominates, is comparable to the gyroscale of the thermal electrons at the edge of the inner EDR. Our approximation of the MMS observations using a steady state, quasi-2-D, tailward retreating X-line was valid only for about 1.4 s. This suggests that the inner EDR is localized; that is, electron outflow jet braking takes place within an ion inertia scale from the X-line. The existence of multiple events or current sheet processes outside the EDR may play an important role in the geometry of reconnection in the near-Earth magnetotail

Particle acceleration by magnetic reconnection in geospace

Particles are accelerated to very high, non-thermal energies during explosive energy-release phenomena in space, solar, and astrophysical plasma environments. While it has been established that magnetic reconnection plays an important role in the dynamics of Earth's magnetosphere, it remains unclear how magnetic reconnection can further explain particle acceleration to non-thermal energies. Here we review recent progress in our understanding of particle acceleration by magnetic reconnection in Earth's magnetosphere. With improved resolutions, recent spacecraft missions have enabled detailed studies of particle acceleration at various structures such as the diffusion region, separatrix, jets, magnetic islands (flux ropes), and dipolarization front. With the guiding-center approximation of particle motion, many studies have discussed the relative importance of the parallel electric field as well as the Fermi and betatron effects. However, in order to fully understand the particle acceleration mechanism and further compare with particle acceleration in solar and astrophysical plasma environments, there is a need for further investigation of, for example, energy partition and the precise role of turbulence.Comment: Submitted to Space Science Review

Near-Earth plasma sheet boundary dynamics during substorm dipolarization.

We report on the large-scale evolution of dipolarization in the near-Earth plasma sheet during an intense (AL ~ -1000 nT) substorm on August 10, 2016, when multiple spacecraft at radial distances between 4 and 15 R E were present in the night-side magnetosphere. This global dipolarization consisted of multiple short-timescale (a couple of minutes) B z disturbances detected by spacecraft distributed over 9 MLT, consistent with the large-scale substorm current wedge observed by ground-based magnetometers. The four spacecraft of the Magnetospheric Multiscale were located in the southern hemisphere plasma sheet and observed fast flow disturbances associated with this dipolarization. The high-time-resolution measurements from MMS enable us to detect the rapid motion of the field structures and flow disturbances separately. A distinct pattern of the flow and field disturbance near the plasma boundaries was found. We suggest that a vortex motion created around the localized flows resulted in another field-aligned current system at the off-equatorial side of the BBF-associated R1/R2 systems, as was predicted by the MHD simulation of a localized reconnection jet. The observations by GOES and Geotail, which were located in the opposite hemisphere and local time, support this view. We demonstrate that the processes of both Earthward flow braking and of accumulated magnetic flux evolving tailward also control the dynamics in the boundary region of the near-Earth plasma sheet.Graphical AbstractMultispacecraft observations of dipolarization (left panel). Magnetic field component normal to the current sheet (BZ) observed in the night side magnetosphere are plotted from post-midnight to premidnight region: a GOES 13, b Van Allen Probe-A, c GOES 14, d GOES 15, e MMS3, g Geotail, h Cluster 1, together with f a combined product of energy spectra of electrons from MMS1 and MMS3 and i auroral electrojet indices. Spacecraft location in the GSM X-Y plane (upper right panel). Colorcoded By disturbances around the reconnection jets from the MHD simulation of the reconnection by Birn and Hesse (1996) (lower right panel). MMS and GOES 14-15 observed disturbances similar to those at the location indicated by arrows

Bubble-Wall Plot: A New Tool for Data Visualization

This research aimed to design a new tool for data visualization with performed features - named Bubble-Wall Plot and assumed that it could be an effective tool for developing data visualization systems. This research reviewed seven data visualization approaches for identifying the outliers, including Line Charts, Parallel Coordinates Plot, Scatter Plots, TreeMap, Glyphs, Pixel-based techniques, and Redial visualizations. The challenges for current data visualization approaches were also summarized. Two principles were addressed to design the new tool- keep it simple strategy with the smallest strategy. As a result, the newly designed Bubble-Wall Plot has successfully been adopted to develop a warning system for identifying the outliers in a Case Study company, which was deployed for user acceptance testing in May 2021. The main contribution is that this newly designed tool with the simplest style was well-designed and proven to effectively develop a warning visualization system

Dayside response of the magnetosphere to a small shock compression: Van Allen Probes, Magnetospheric MultiScale, and GOES-13.

Observations from Magnetospheric MultiScale (~8 Re) and Van Allen Probes (~5 and 4 Re) show that the initial dayside response to a small interplanetary shock is a double-peaked dawnward electric field, which is distinctly different from the usual bipolar (dawnward and then duskward) signature reported for large shocks. The associated E × B flow is radially inward. The shock compressed the magnetopause to inside 8 Re, as observed by Magnetospheric MultiScale (MMS), with a speed that is comparable to the E × B flow. The magnetopause speed and the E × B speeds were significantly less than the propagation speed of the pulse from MMS to the Van Allen Probes and GOES-13, which is consistent with the MHD fast mode. There were increased fluxes of energetic electrons up to several MeV. Signatures of drift echoes and response to ULF waves also were seen. These observations demonstrate that even very weak shocks can have significant impact on the radiation belts