Phosphorylation of Tyrosine 841 Strongly Affects JAK3 Kinase’s Activation

Janus Kinase 3 (JAK3) plays a key role in the proliferation, development, and differentiation of various cells. It regulates gene expression by phosphorylation of Signal Transducer and Activators of Transcriptions (STATs). A new JAK3 kinase domain phosphorylation site was found, tyrosine-841 (Y841). The effects of phosphorylated tyrosine-841 (pY841) on ATP/ADP binding affinities of the JAK3 kinase domain were systematically studied and reported here. With the support of TACC, we applied long all-atom molecular dynamic simulations to study the effects of phosphorylation on Y841. The results show that pY841 reduces the size of the cleft between the N-lobe and C-lobe of the JAK3 kinase domain. However, when an ATP/ADP is bound to the kinase pY841 was found to enlarge the cleft. Additionally, for unphosphorylated JAK3 (JAK3-Y841), the binding forces between the kinase domain and ATP or ADP are similar. After phosphorylation of Y841, JAK3-pY841 exhibits more salt bridges and hydrogen bonds between ATP and kinase than ADP and kinase. Consequently, the electrostatic binding force between ATP and kinase is higher than that between ADP and kinase. The result is that compared to ADP, ATP is more attractive to JAK3 when Y841 is phosphorylated. Therefore, JAK3-pY841 tends to bind ATP rather than ADP.Texas Advanced Computing Center (TACC

Micromechanics model for predicting effective elastic moduli of porous ceramic matrices with randomly oriented carbon nanotube reinforcements

Multi-step micromechanics-based models are developed to predict the overall effective elastic moduli of porous ceramic with randomly oriented carbon nanotube (CNT) reinforcements. The presence of porosity in the ceramic matrix that has been previously neglected in the literature is considered in present analysis. The ceramic matrix with porosity is first homogenized using a classical Mori-Tanaka model. Then, the homogenized porous ceramic matrix with randomly oriented CNTs is analysed using two micromechanics models. The results predicted by the present models are compared with experimental and analytical results that have been reported in literature. The comparison shows that the discrepancies between the present analytical results and experimental data are about 10% for 4 wt% of CNTs and about 0.5% for 8 wt% CNTs, both substantially lower than the discrepancies currently reported in the literature

Clue: Cross-modal Coherence Modeling for Caption Generation

We use coherence relations inspired by computational models of discourse to study the information needs and goals of image captioning. Using an annotation protocol specifically devised for capturing image--caption coherence relations, we annotate 10,000 instances from publicly-available image--caption pairs. We introduce a new task for learning inferences in imagery and text, coherence relation prediction, and show that these coherence annotations can be exploited to learn relation classifiers as an intermediary step, and also train coherence-aware, controllable image captioning models. The results show a dramatic improvement in the consistency and quality of the generated captions with respect to information needs specified via coherence relations.Comment: Accepted as a long paper to ACL 202

Exact Penalization and Necessary Optimality Conditions for Multiobjective Optimization Problems with Equilibrium Constraints

A calmness condition for a general multiobjective optimization problem with equilibrium constraints is proposed. Some exact penalization properties for two classes of multiobjective penalty problems are established and shown to be equivalent to the calmness condition. Subsequently, a Mordukhovich stationary necessary optimality condition based on the exact penalization results is obtained. Moreover, some applications to a multiobjective optimization problem with complementarity constraints and a multiobjective optimization problem with weak vector variational inequality constraints are given