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Hand pose estimation (HPE) can be used for a variety of human-computer interaction applications such as gesture-based control for physical or virtual/augmented reality devices. Recent works have shown that videos or multi-view images carry rich information regarding the hand, allowing for the development of more robust HPE systems. In this paper, we present the Multi-View Video-Based 3D Hand (MuViHand) dataset, consisting of multi-view videos of the hand along with ground-truth 3D pose labels. Our dataset includes more than 402,000 synthetic hand images available in 4,560 videos. The videos have been simultaneously captured from six different angles with complex backgrounds and random levels of dynamic lighting. The data has been captured from 10 distinct animated subjects using 12 cameras in a semi-circle topology where six tracking cameras only focus on the hand and the other six fixed cameras capture the entire body. Next, we implement MuViHandNet, a neural pipeline consisting of image encoders for obtaining visual embeddings of the hand, recurrent learners to learn both temporal and angular sequential information, and graph networks with U-Net architectures to estimate the final 3D pose information. We perform extensive experiments and show the challenging nature of this new dataset as well as the effectiveness of our proposed method. Ablation studies show the added value of each component in MuViHandNet, as well as the benefit of having temporal and sequential information in the dataset., Comment: 14 pages, 15 figures

Apart from its literary context, the parable of the Good Samaritan is commonly understood to teach a simple moral: act like the Samaritan. Closer attention to its Lukan context, however, reveals that this parable is serving the larger purpose of teaching one how to interpret the Law, made particularly evident by the questions that closely precede the parable: "What is in the Law, and how do you read it?" Through a close reading of the parable's grammar, structure, and narrative context, one discovers that the parable illustrates how life-giving interpretation of Torah is characterized by compassion, action, and solidarity with the suffering. The priest and Levite function as foils—those whose embodiment of the Law attests to a distorted interpretation of Torah. The Samaritan, in contrast, embodies a surprisingly exemplary reading of Torah. There is also good reason to suspect another twist at the end of the parable, one that invites the reader to adopt the point of view of the parable's victim, thereby teaching that proper interpretation of the Law must take into account the perspective of the suffering and marginalized.

This article opens with an example of what a Christian interpretive paradigm might look like. For help with this, it turns to Augustine's De Doctrina Christiana (DDC), which will be shown to have a hermeneutic with a priori theological convictions. Augustine's ecclesially located exegetical framework results in a hermeneutic that (1) calls for humble, submissive, and virtuous readers; (2) highly values authorial communicative intent; (3) is nonetheless open to polysemy; and (4) delimits interpretations by appealing to the rule of faith, the double love commandment, and clearer canonical texts. Insights from DDC are then brought into conversation with the hermeneutical paradigms of Räisänen and Stendahl. In brief, Augustine's hermeneutic clashes with Räisänen's, because Augustine reads Scripture from the standpoint of Christian faith, whereas Räisänen attempts to read from a so-called neutral standpoint. Regarding Stendahl's exclusive privileging of authorial intent, an ecclesially located theology would seem to challenge Stendahl because of (1) how NT writers often seem to read OT texts beyond the intent of the OT author, and (2) the inability of sola scriptura to determine crucial theological doctrines. The last section of this article notes how Augustine's approach to delimiting polysemic interpretations holds together many of the strengths offered by contemporary theological interpreters, including Max Turner, Richard Hays, Joel Green, Stephen Fowl, A. K. M. Adam, Richard Briggs, and others. The hope is that, by bringing DDC into the conversation, this article can contribute to the elusive task of making room for, while simultaneously bounding, polysemy in biblical interpretation.

Background Constitutive activation of Ras in immortalized bronchial epithelial cells increases electron transport chain activity, oxygen consumption and tricarboxylic acid cycling through unknown mechanisms. We hypothesized that members of the Ras family may stimulate respiration by enhancing the expression of the Vb regulatory subunit of cytochrome c oxidase (COX). Results We found that the introduction of activated H-RasV12 into immortalized human bronchial epithelial cells increased eIF4E-dependent COX Vb protein expression simultaneously with an increase in COX activity and oxygen consumption. In support of the regulation of COX Vb expression by the Ras family, we also found that selective siRNA-mediated inhibition of K-Ras expression in A549 lung adenocarcinoma cells reduced COX Vb protein expression, COX activity, oxygen consumption and the steady-state concentration of ATP. We postulated that COX Vb-mediated activation of COX activity may be required for the anchorage-independent growth of A549 cells as soft agar colonies or as lung xenografts. We transfected the A549 cells with COX Vb small interfering or shRNA and observed a significant reduction of their COX activity, oxygen consumption, ATP and ability to grow in soft agar and as poorly differentiated tumors in athymic mice. Conclusion Taken together, our findings indicate that the activation of Ras increases COX activity and mitochondrial respiration in part via up-regulation of COX Vb and that this regulatory subunit of COX may have utility as a Ras effector target for the development of anti-neoplastic agents.

The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1) is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1), and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However – in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins., Author Summary The malaria parasite invades red blood cells. During invasion several parasite proteins, including a vaccine candidate called PfAMA1, are clipped from the parasite surface. Most of this clipping is performed by an enzyme called PfSUB2, but some also occurs through intramembrane cleavage. The function of this shedding is unknown. We have examined the requirements for shedding of PfAMA1, and the effects of mutations that block shedding. Mutations that block intramembrane cleavage have no effect on the parasite. We then show that PfSUB2 does not recognise a specific amino acid sequence in PfAMA1, but rather cleaves it at a position determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site prevent shedding, and parasites expressing non-cleavable PfAMA1 along with unmodified PfAMA1 grow normally. However, these mutations cannot be introduced into the parasite's genome, showing that some shedding by PfSUB2 is essential for parasite survival. Parasites expressing shedding-resistant mutants of PfAMA1 show enhanced sensitivity to invasion-inhibitory antibodies, suggesting that shedding of surface proteins during invasion helps the parasite to evade potentially protective antibodies. Drugs that inhibit PfSUB2 may prevent disease and enhance the efficacy of vaccines based on PfAMA1.

Choline is an essential anabolic substrate for the synthesis of phospholipids. Choline kinase phosphorylates choline to phosphocholine that serves as a precursor for the production of phosphatidylcholine, the major phospholipid constituent of membranes and substrate for the synthesis of lipid signaling molecules. Nuclear magnetic resonance (NMR)-based metabolomic studies of human tumors have identified a marked increase in the intracellular concentration of phosphocholine relative to normal tissues. We postulated that the observed intracellular pooling of phosphocholine may be required to sustain the production of the pleiotropic lipid second messenger, phosphatidic acid. Phosphatidic acid is generated from the cleavage of phosphatidylcholine by phospholipase D2 and is a key activator of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT survival signaling pathways. In this study we show that the steady-state concentration of phosphocholine is increased by the ectopic expression of oncogenic H-Ras(V12) in immortalized human bronchial epithelial cells. We then find that small interfering RNA (siRNA) silencing of choline kinase expression in transformed HeLa cells completely abrogates the high concentration of phosphocholine, which in turn decreases phosphatidylcholine, phosphatidic acid and signaling through the MAPK and PI3K/AKT pathways. This simultaneous reduction in survival signaling markedly decreases the anchorage-independent survival of HeLa cells in soft agar and in athymic mice. Last, we confirm the relative importance of phosphatidic acid for this pro-survival effect as phosphatidic acid supplementation fully restores MAPK signaling and partially rescues HeLa cells from choline kinase inhibition. Taken together, these data indicate that the pooling of phosphocholine in cancer cells may be required to provide a ready supply of phosphatidic acid necessary for the feed-forward amplification of cancer survival signaling pathways. James Graham Brown Cancer Center United States Department of Health & Human Services National Institutes of Health (NIH) - USA (1 R01 CA11642801) Kentucky Lung Cancer Research Program

Parkinson's disease is a debilitating movement disorder characterized by altered levels of alpha(6)beta(2) * ( * indicates the possible presence of additional subunits) nicotinic acetylcholine receptors (nAChRs) localized on presynaptic striatal catecholaminergic neurons. alpha-Conotoxin MII (alpha-CTx MII) is a highly useful ligand to probe alpha(6)beta(2) nAChRs structure and function, but it does not discriminate among closely related alpha(6) * nAChR subtypes. Modification of the alpha-CTx MII primary sequence led to the identification of alpha-CTx MII[E11A], an analog with 500-5300-fold discrimination between alpha(6) * subtypes found in both human and non-human primates. alpha-CTx MII[E11A] binds most strongly (femtomolar dissociation constant) to the high affinity alpha(6) nAChR, a subtype that is selectively lost in Parkinson's disease. Here, we present the three-dimensional solution structure for alpha-CTx MII[E11A] as determined by two-dimensional (1)H NMR spectroscopy to 0.13+/-0.09A backbone and 0.45+/-0.08A heavy atom root-mean-square deviation from mean structure. Structural comparisons suggest that the increased hydrophobic area of alpha-CTx MII[E11A] relative to other members of the alpha-CTx family may be responsible for its exceptionally high affinity for alpha6alpha4beta2 * nAChR as well as discrimination between alpha(6)beta(2) and alpha(3)beta(2) containing nAChRs. This finding may enable the rational design of novel peptide analogs that demonstrate enhanced specificity for alpha(6) * nAChR subunit interfaces and provide a means to better understand nAChR structural determinants that modulate brain dopamine levels and the pathophysiology of Parkinson's disease.