Tv-RIO1 – an atypical protein kinase from the parasitic nematode Trichostrongylus vitrinus

Background: Protein kinases are key enzymes that regulate a wide range of cellular processes, including cell-cycle progression, transcription, DNA replication and metabolic functions. These enzymes catalyse the transfer of phosphates to serine, threonine and tyrosine residues, thus playing functional roles in reversible protein phosphorylation. There are two main groups, namely eukaryotic protein kinases (ePKs) and atypical protein kinases (aPKs); RIO kinases belong to the latter group. While there is some information about RIO kinases and their roles in animals, nothing is known about them in parasites. This is the first study to characterise a RIO1 kinase from any parasite. Results: A full-length cDNA (Tv-rio-1) encoding a RIO1 protein kinase (Tv-RIO1) was isolated from the economically important parasitic nematode Trichostrongylus vitrinus (Order Strongylida). The uninterrupted open reading frame (ORF) of 1476 nucleotides encoded a protein of 491 amino acids, containing the characteristic RIO1 motif LVHADLSEYNTL. Tv-rio-1 was transcribed at the highest level in the third-stage larva (L3), and a higher level in adult females than in males. Comparison with homologues from other organisms showed that protein Tv-RIO1 had significant homology to related proteins from a range of metazoans and plants. Amino acid sequence identity was most pronounced in the ATP-binding motif, active site and metal binding loop. Phylogenetic analyses of selected amino acid sequence data revealed Tv-RIO1 to be most closely related to the proteins in the species of Caenorhabditis. A structural model of Tv-RIO1 was constructed and compared with the published crystal structure of RIO1 of Archaeoglobus fulgidus (Af-Rio1). Conclusion: This study provides the first insights into the RIO1 protein kinases of nematodes, and a foundation for further investigations into the biochemical and functional roles of this molecule in biological processes in parasitic nematodes

The investigation of saccade parallel programming using a novel double-step paradigm: an fMRI study

Introduction: This study investigated the neuronal mechanisms of saccade target remapping and decision- making process in relation to parallel programming of saccades. Our previous study (Hu & Walker, 2011) showed that the frontal and parietal eye fields were both involved in pre-programmed of saccade sequences. It has been suggested that the representation of the second saccade goal in the double-step paradigm may involve the process of saccade target re-mapping (Duhamel, Colby, & Goldberg, 1992). In this study, we have developed a novel double-step paradigm enable us to be able to examine the neuronal mechanism underlying saccade target remapping process that required for second saccades to be executed correctly. Methods: Fifteen participants completed a novel double-step task in a 3T MRI scanner. Anatomical scans (T1 weighted) were acquired for each participant before the functional scans (TR = 1830 ms, TE = 5.5ms, resolution = 256*256, flip angle of 11°, number of slices = 160, field of view = 256*256). Functional data were collected from the whole brain using echo-planar (EPI) images with voxel size of 3*3*3 mm (TR = 3000 ms, TE = 32 ms, resolution = 64*64, field of view = 192*192, flip angle = 90°, number of slices = 42). For each participant, 73 volumes were acquired in an interleaved sequence per session. Different double-step saccade trials were as follows: 1) saccades required both target remapping and change-of-plan (saccade to an alternative target); 2) saccades required target remapping but no change-of-plan; 3) saccades required change-of-plan but not target remapping (when a return saccade to the origin or a saccade to an alternative target with vector the same as the original one was made); 4) saccades required neither target remapping nor change-of-plan. Contrasting the BOLD signal between these trial types examined the neural basis of the saccade target remapping and change-of-plan processes. Results: FMRI data were analyzed using SPM5 (functional imaging laboratory, UCL, 2005) based on Matlab 6.5 (The MathWorks, 2002). Realignment (2nd Degree B-Spline interpolation), normalization (MNI space) and spatial smoothing (8mm Gaussian smoothing kernel) were carried out as data pre- processing. First level analysis used general linear model (GLM) and each trial type was modelled as one regressor in addition to the six head movement regressors. Four key contrast were carried out to examine the cognitive process of interest: saccade target remapping & change-of-plan processes. Results showed that the right superior parietal, temporal and hippocampus regions were involved in saccade target remapping. Left lateral prefrontal, left pre-motor region, right ventromedial frontal cortex, right frontal eye fields and bilateral parietal eye fields were involved in saccade target decision processes. Behavioural results supported the view that second saccades could be partially preprogrammed, in parallel with the first step, regardless if a change-of-plan was required or not. Conclusions: In conclusion, the findings support the role of the superior parietal region in the saccade target remapping process while the hippocampus area may be involved as a temporal storage to store the original vectors required for the spatial remapping process. The saccade target decision process required a network of both prefrontal executive function regions and saccade related regions

Towards standard imsets for maximal ancestral graphs

The imsets of Studen\'y (2005) are an algebraic method for representing conditional independence models. They have many attractive properties when applied to such models, and they are particularly nice for working with directed acyclic graph (DAG) models. In particular, the 'standard' imset for a DAG is in one-to-one correspondence with the independences it induces, and hence is a label for its Markov equivalence class. We first present a proposed extension to standard imsets for maximal ancestral graph (MAG) models, using the parameterizing set representation of Hu and Evans (2020). In these cases the imset provides a scoring criteria by measuring the discrepancy for a list of independences that define the model; this gives an alternative to the usual BIC score that is also consistent, and much easier to compute. We also show that, of independence models that do represent the MAG, the imset we give is minimal. Unfortunately, for some graphs the representation does not represent all the independences in the model, and in certain cases does not represent any at all. For these general MAGs, we refine the reduced ordered local Markov property Richardson (2003) by a novel graphical tool called _power DAGs_, and this results in an imset that induces the correct model and which, under a mild condition, can be constructed in polynomial time.Comment: Accepted to Bernoulli, 58 pages, 17 figure

Nonadopters of Online Social Network Services: Is It Easy to Have Fun Yet?

Although online social network services (OSNS), e.g., Facebook, Twitter, MySpace, LinkedIn, are enjoying rampant popularity, a subsection of the population (i.e., nonadopters) continues to forgo using them. Our study is one of the first to focus exclusively on what might motivate nonadopters to accept a widely adopted IT. By considering nonadopters’ inertia within the context of early stages of innovation diffusion and incorporating status quo bias theory into well-established technology acceptance model (TAM) relationships, this study uncovers the finding that people who report that they do not use OSNS would use them if they thought OSNS were easier and more enjoyable to use, and if they were persuaded by others to use them. Our findings suggest these nonadopters do not see the usefulness of OSNS, risks of sharing personal information publically, or the perceived amount of effort in using OSNS as factors that influence potential acceptance and use of the technology. This study contributes to research by offering an integrated theoretical framework that updates TAM with status quo bias theory to study nonadopters and offers IS practice guidelines for OSNS providers to attract nonadopters to accept and use the technology

Doubly Robust Kernel Statistics for Testing Distributional Treatment Effects Even Under One Sided Overlap

As causal inference becomes more widespread the importance of having good tools to test for causal effects increases. In this work we focus on the problem of testing for causal effects that manifest in a difference in distribution for treatment and control. We build on work applying kernel methods to causality, considering the previously introduced Counterfactual Mean Embedding framework (\textsc{CfME}). We improve on this by proposing the \emph{Doubly Robust Counterfactual Mean Embedding} (\textsc{DR-CfME}), which has better theoretical properties than its predecessor by leveraging semiparametric theory. This leads us to propose new kernel based test statistics for distributional effects which are based upon doubly robust estimators of treatment effects. We propose two test statistics, one which is a direct improvement on previous work and one which can be applied even when the support of the treatment arm is a subset of that of the control arm. We demonstrate the validity of our methods on simulated and real-world data, as well as giving an application in off-policy evaluation.Comment: 9 pages, Preprin

Generalized Quantum Geometric Tensor in a Non-Hermitian Exciton-Polariton System

In this work, we review two different generalizations of a quantum geometric tensor (QGT) in two-band non-Hermitian systems and apply the formalism to the system of microcavity exciton polaritons. In particular, we extend the existing method of measuring the QGT that uses the pseudospins in photonic and polaritonic systems. We find that both forms of the generalized QGT can be expressed in terms of the exciton-polariton pseudospin components, which can be experimentally measured. We then present the generalized QGT components, i.e. the quantum metric and Berry curvature, for an exemplar non-Hermitian exciton-polariton system. Our simulations of the wave packet dynamics in this exciton-polariton system show that the right-right Berry curvature gives a more accurate description of the anomalous Hall drift.Comment: 2