Challenges and Opportunities for CubeSat Detection for Space Situational Awareness using a CNN

The deployment of artificial neural networks (ANNs) on small satellites will improve space situational awareness (SSA) where scarce radio resources limits the interactions between space-born and ground-based systems. The application of ANNs in space is stymied by lack of curated datasets. This project addresses an ongoing problem of small spacecraft detection and identification. This paper will present the problem and the activities the team has taken to advance this field

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

Subdivision of the neuroectoderm into three rows of cells along the dorsal-ventral axis by neural identity genes is a highly conserved developmental process. While neural identity genes are expressed in remarkably similar patterns in vertebrates and invertebrates, previous work suggests that these patterns may be regulated by distinct upstream genetic pathways. Here we ask whether a potential conserved source of positional information provided by the BMP signaling contributes to patterning the neuroectoderm. We have addressed this question in two ways: First, we asked whether BMPs can act as bona fide morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion, and second, we examined whether BMPs might act in a similar fashion in patterning the vertebrate neuroectoderm. In this study, we show that graded BMP signaling participates in organizing the neural axis in Drosophila by repressing expression of neural identity genes in a threshold-dependent fashion. We also provide evidence for a similar organizing activity of BMP signaling in chick neural plate explants, which may operate by the same double negative mechanism that acts earlier during neural induction. We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes

A General, Enantioselective Synthesis of Protected Morpholines and Piperazines

A short, high yielding protocol has been developed for the enantioselective and general synthesis of C2-functionalized, benzyl protected morpholines and orthogonally <i>N,N′</i>-protected piperazines from a common intermediate

Synthesis of indole derived protease-activated receptor 4 antagonists and characterization in human platelets.

Protease activated receptor-4 (PAR4) is one of the thrombin receptors on human platelets and is a potential target for the management of thrombotic disorders. We sought to develop potent, selective, and novel PAR4 antagonists to test the role of PAR4 in thrombosis and hemostasis. Development of an expedient three-step synthetic route to access a novel series of indole-based PAR4 antagonists also necessitated the development of a platelet based high-throughput screening assay. Screening and subsequent structure activity relationship analysis yielded several selective PAR4 antagonists as well as possible new scaffolds for future antagonist development

Platelet Lipidomic Profiling: Novel Insight into Cytosolic Phospholipase A₂α Activity and Its Role in Human Platelet Activation

With a newer, more selective and efficacious cytosolic phospholipase A₂α (cPLA₂α) inhibitor available, we revisited the role of cPLA₂α activity in platelet activation and discovered that a component of platelet signaling, even larger than previously appreciated, relies on this enzyme. In a whole blood shear-based flow chamber assay, giripladib, a cPLA₂α inhibitor, reduced platelet adhesion and accumulation on collagen. Moreover, giripladib differentially affected P-selectin expression and GPIIbIIIa activation depending on the agonist employed. While protease-activated receptor 1 (PAR1)-mediated platelet activation was unaffected by giripladib, the levels of PAR4- and GPVI-mediated platelet activation were significantly reduced. Meanwhile, the thromboxane A₂ receptor antagonist SQ29548 had no effect on PAR-, GPVI-, or puriniergic receptor-mediated platelet activation, suggesting that another eicosanoid produced downstream of arachidonic acid liberation by cPLA₂α was responsible for this large component of PAR4- and GPVI-mediated platelet activation. In parallel, we profiled PAR-mediated changes in glycerophospholipid (GPL) mass with and without giripladib to better understand cPLA₂α-mediated lipid metabolism. Phosphatidylcholine and phosphatidylethanolamine (PE) demonstrated the largest consumption of mass during thrombin stimulation. Additionally, we confirm phosphatidylinositol as a major substrate of cPLA₂α. A comparison of PAR1- and PAR4-induced metabolism revealed the consumption of more putative arachidonyl-PE species downstream of PAR1 activation. Instead of enhanced cPLA₂α activity and therefore more arachidonic acid liberation downstream of PAR4, these results indicate the major role that cPLA₂α activity plays in platelet function and suggest that a novel eicosanoid is produced in response to platelet activation that represents a large component of PAR4- and GPVI-mediated responses

Dual PAR1/PAR4 inhibition significantly inhibits thrombin mediated platelet activation.

<p>Platelets were treated with PAR1 antagonist RWJ-56110 or PAR4 full antagonists either alone or in combination prior to stimulation with 10 nM thrombin for 10 minutes. GPIIbIIIa activation was measured, data reported is mean ± S.E.M. n of 3 volunteers. One sample t-test for significant deviation from DMSO control p-values *p<0.05, **p<0.005.</p

1, 3, and 5 are full PAR4 antagonists.

<p>1, 3, and 5 were compared with YD-3 potency against PAR1 and PAR4 mediated GPIIbIIIa activation and P-selectin expression. Platelets were treated with compound or DMSO control for 5 minutes prior to stimulation with 20 µM PAR1-AP (left panels) or 200 µM PAR4-AP (right panels) for 10 minutes. GPIIbIIIa activation (black) and P-selectin expression (grey) in PAR activated platelets by flow cytometry. The order of potency for PAR4 antagonism is YD-3>1>5>3. Values are displayed as mean±S.E.M. n of 3 volunteers performed in singlicate.</p

High throughput platelet calcium mobilization identifies novel indole derived PAR4 antagonists.

<p>A. To determine the Z-factor, and thus the usefulness of the assay as a screening tool, platelets were treated with either vehicle (calcium assay buffer) or 80 µM PAR4-AP in checkerboard fashion in a 384 well plate. Representative data from 1 donor is displayed as mean ± S.D. using 192 replicates of each condition in a single plate. Z-factor of the represented sample is 0.35 and a second volunteer (data not shown) was 0.31. B. Platelets were treated with 10 µM YD-3 for the indicated period of time followed by stimulation with 80 µM PAR4-AP. Data represented is an n of 2 volunteers, mean ± S.D. performed in triplicate. Means are significantly different where indicated. Unpaired one-tailed t-test: time points versus DMSO treated control ***p<0.0001. Unpaired one-tailed t-test: time points versus 12 minute time point ^#p<0.05. C. Representative tracings of platelets treated with DMSO or 10 µM YD-3 for 6 minutes followed by stimulation with 80 µM PAR4-AP. D. Compounds were screened by treating platelets with 10 µM compound or DMSO control followed by challenge with 80 µM PAR4-AP. Data represented as percent 80 µM PAR4 response n of 2 volunteers mean±S.D. Compounds that displayed greater than 50% inhibitory activity (below dashed line) were subject to further investigation.</p

Synthetic scheme for YD-3 and novel compounds.

<p>Reagents and conditions. (a) 1.2 equiv. Ar (Het)CH₂Br, 1.2 equiv. NaH, rt, 40 min, 39–65%; (b) 1.1 equiv. NBS, 4°C, 16h, 76–90%; (c) 10 mol% Pd₂(dba)₃, 20 mol% PCy₃, 1.1 equiv. Ar(Het)B(OH)₂ or Ar(Het)B(OR)₂, 1.7 equiv. K₃PO₄, dioxane/H₂O, mw, 120°C, 30 min, 17–56%. U,V,W,X,Y,Z = CH or N. YD-3: U,V,W,X,Y =  CH, Z = N, R₂ = CH₂COOCH₂CH_3.</p