The role of epidermal growth factor-like module containing mucin-like hormone receptor 2 in human cancers.

G-protein coupled receptors (GPCRs) are among the most diverse and ubiquitous proteins in all of biology. The epidermal growth factor-seven span transmembrane (EGF-TM7) subfamily of adhesion GPCRs is a small subset whose members are mainly expressed on the surface of leukocytes. The EGF domains on the N-terminus add significant size to these receptors and they are considered to be among the largest members of the TM7 family. Although not all of their ligands or downstream targets have been identified, there is evidence implicating the EGF-TM7 family diverse processes such as cell adhesion, migration, inflammation, and autoimmune disease. Recent studies have identified expression of EGF-TM7 family members on human neoplasms including those of the thyroid, stomach, colon, and brain. Their presence on these tissues is not surprising given the ubiquity of GPCRs, but because their functional significance and pathways are not completely understood, they are of tremendous clinical and scientific interest. Current evidence suggests that expression of certain EGF-TM7 receptors is correlated with tumor grade, confers a more invasive phenotype, and increases the likelihood of metastatic disease. In this review, we will discuss the structure, function, and regulation of these receptors. We also describe the expression of these receptors in human cancers and explore their potential mechanistic significance

Prototype of Fault Adaptive Embedded Software for Large-Scale Real-Time Systems

This paper describes a comprehensive prototype of large-scale fault adaptive embedded software developed for the proposed Fermilab BTeV high energy physics experiment. Lightweight self-optimizing agents embedded within Level 1 of the prototype are responsible for proactive and reactive monitoring and mitigation based on specified layers of competence. The agents are self-protecting, detecting cascading failures using a distributed approach. Adaptive, reconfigurable, and mobile objects for reliablility are designed to be self-configuring to adapt automatically to dynamically changing environments. These objects provide a self-healing layer with the ability to discover, diagnose, and react to discontinuities in real-time processing. A generic modeling environment was developed to facilitate design and implementation of hardware resource specifications, application data flow, and failure mitigation strategies. Level 1 of the planned BTeV trigger system alone will consist of 2500 DSPs, so the number of components and intractable fault scenarios involved make it impossible to design an `expert system' that applies traditional centralized mitigative strategies based on rules capturing every possible system state. Instead, a distributed reactive approach is implemented using the tools and methodologies developed by the Real-Time Embedded Systems group.Comment: 2nd Workshop on Engineering of Autonomic Systems (EASe), in the 12th Annual IEEE International Conference and Workshop on the Engineering of Computer Based Systems (ECBS), Washington, DC, April, 200

GPU accelerated real-time multi-functional spectral-domain optical coherence tomography system at 1300 nm.

We present a GPU accelerated multi-functional spectral domain optical coherence tomography system at 1300 nm. The system is capable of real-time processing and display of every intensity image, comprised of 512 pixels by 2048 A-lines acquired at 20 frames per second. The update rate for all four images with size of 512 pixels by 2048 A-lines simultaneously (intensity, phase retardation, flow and en face view) is approximately 10 frames per second. Additionally, we report for the first time the characterization of phase retardation and diattenuation by a sample comprised of a stacked set of polarizing film and wave plate. The calculated optic axis orientation, phase retardation and diattenuation match well with expected values. The speed of each facet of the multi-functional OCT CPU-GPU hybrid acquisition system, intensity, phase retardation, and flow, were separately demonstrated by imaging a horseshoe crab lateral compound eye, a non-uniformly heated chicken muscle, and a microfluidic device. A mouse brain with thin skull preparation was imaged in vivo and demonstrated the capability of the system for live multi-functional OCT visualization

A GABAergic projection from the centromedial nuclei of the amygdala to ventromedial prefrontal cortex modulates reward behavior

The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors. However, the CeMA and ventromedial PFC (vmPFC) interaction in reward regulation remains poorly understood. Here, we identify and dissect a GABAergic projection that originates in the CeMA and terminates in the vmPFC (VGat-Cre(CeMA-vmPFC)) using viral-vector-mediated, cell-type-specific optogenetic techniques in mice. Pathway-specific optogenetic activation of the VGat-Cre(CeMA-vmPFC) circuit in awake, behaving animals produced a positive, reward-like phenotype in real-time place preference and increased locomotor activity in open-field testing. In sucrose operant conditioning, the photoactivation of these terminals increased nose-poking effort with no effect on licking behavior and robustly facilitated the extinction of operant behavior. However, photoactivation of these terminals did not induce self-stimulation in the absence of an external reward. The results described here suggest that the VGat-Cre(CeMA-vmPFC) projection acts to modulate existing reward-related behaviors. SIGNIFICANCE STATEMENT Many studies have shown that the interactions between the centromedial nucleus of the amygdala (CeMA) and ventromedial PFC (vmPFC) have critical roles for emotional regulation. However, most studies have associated this circuit with fear and anxiety behaviors and emphasized top-down processing from vmPFC to CeMA. Here, we provide new evidence for bottom-up CeMA to vmPFC influence on reward-related behaviors. Although previous work implicated the CeMA in incentive salience, our results isolate the investigation to a specific CeMA GABAergic projection to the vmPFC. This long-range GABAergic interaction between amygdala and frontal cortex adds a new dimension to the complex regulation of reward-related behaviors

Prototype of Fault Adaptive Embedded Software for Large-Scale Real-Time Systems

This paper describes a comprehensive prototype of large-scale fault adaptive embedded software developed for the proposed Fermilab BTeV high energy physics experiment. Lightweight self-optimizing agents embedded within Level 1 of the prototype are responsible for proactive and reactive monitoring and mitigation based on specified layers of competence. The agents are self-protecting, detecting cascading failures using a distributed approach. Adaptive, reconfigurable, and mobile objects for reliability are designed to be self-configuring to adapt automatically to dynamically changing environments. These objects provide a self-healing layer with the ability to discover, diagnose, and react to discontinuities in real-time processing. A generic modeling environment was developed to facilitate design and implementation of hardware resource specifications, application data flow, and failure mitigation strategies. Level 1 of the planned BTeV trigger system alone will consist of 2500 DSPs, so the number of components and intractable fault scenarios involved make it impossible to design an “expert system” that applies traditional centralized mitigative strategies based on rules capturing every possible system state. Instead, a distributed reactive approach is implemented using the tools and methodologies developed by the RealTime Embedded Systems group

The shadow knows: using shadows to investigate the structure of the pretransitional disk of HD 100453

We present GPI polarized intensity imagery of HD 100453 in Y-, J-, and K1 bands which reveals an inner gap ($9 - 18$ au), an outer disk ($18-39$ au) with two prominent spiral arms, and two azimuthally-localized dark features also present in SPHERE total intensity images (Wagner 2015). SED fitting further suggests the radial gap extends to $1$ au. The narrow, wedge-like shape of the dark features appears similar to predictions of shadows cast by a inner disk which is misaligned with respect to the outer disk. Using the Monte Carlo radiative transfer code HOCHUNCK3D (Whitney 2013), we construct a model of the disk which allows us to determine its physical properties in more detail. From the angular separation of the features we measure the difference in inclination between the disks 45$^{\circ}$, and their major axes, PA = 140$^{\circ}$ east of north for the outer disk and 100$^{\circ}$for the inner disk. We find an outer disk inclination of $25 \pm 10^{\circ}$ from face-on in broad agreement with the Wagner 2015 measurement of 34$^{\circ}$. SPHERE data in J- and H-bands indicate a reddish disk which points to HD 100453 evolving into a young debris disk

The BAT AGN Spectroscopic Survey -- XVIII. Searching for Supermassive Black Hole Binaries in the X-rays

Theory predicts that a supermassive black hole binary (SMBHB) could be observed as a luminous active galactic nucleus (AGN) that periodically varies on the order of its orbital timescale. In X-rays, periodic variations could be caused by mechanisms including relativistic Doppler boosting and shocks. Here we present the first systematic search for periodic AGNs using $941$ hard X-ray light curves (14-195 keV) from the first 105 months of the Swift Burst Alert Telescope (BAT) survey (2004-2013). We do not find evidence for periodic AGNs in Swift-BAT, including the previously reported SMBHB candidate MCG+11$-$11$-$032. We find that the null detection is consistent with the combination of the upper-limit binary population in AGNs in our adopted model, their expected periodic variability amplitudes, and the BAT survey characteristics. We have also investigated the detectability of SMBHBs against normal AGN X-ray variability in the context of the eROSITA survey. Under our assumptions of a binary population and the periodic signals they produce which have long periods of hundreds of days, up to $13$% true periodic binaries can be robustly distinguished from normal variable AGNs with the ideal uniform sampling. However, we demonstrate that realistic eROSITA sampling is likely to be insensitive to long-period binaries because longer observing gaps reduce their detectability. In contrast, large observing gaps do not diminish the prospect of detecting binaries of short, few-day periods, as 19% can be successfully recovered, the vast majority of which can be identified by the first half of the survey.Comment: 17 pages, including 8 figures and 4 tables. Accepted for publication in Ap