Wave-packet propagation based calculation of above-threshold ionization in the x-ray regime

We investigate the multi-photon process of above-threshold ionization for the light elements hydrogen, carbon, nitrogen and oxygen in the hard x-ray regime. Numerical challenges are discussed and by comparing Hartree-Fock-Slater calculations to configuration-interaction-singles results we justify the mean-field potential approach in this regime. We present a theoretical prediction of two-photon above-threshold-ionization cross sections for the mentioned elements. Moreover, we study how the importance of above-threshold ionization varies with intensity. We find that for carbon, at x-ray intensities around $10^{23}{\rm Wcm}^{-2}$, two-photon above-threshold ionization of the K-shell electrons is as probable as one-photon ionization of the L-shell electrons.Comment: 13 pages, 4 figures, 1 tabl

Artificial Neuronal Ensembles with Learned Context Dependent Gating

Biological neural networks are capable of recruiting different sets of neurons to encode different memories. However, when training artificial neural networks on a set of tasks, typically, no mechanism is employed for selectively producing anything analogous to these neuronal ensembles. Further, artificial neural networks suffer from catastrophic forgetting, where the network's performance rapidly deteriorates as tasks are learned sequentially. By contrast, sequential learning is possible for a range of biological organisms. We introduce Learned Context Dependent Gating (LXDG), a method to flexibly allocate and recall `artificial neuronal ensembles', using a particular network structure and a new set of regularization terms. Activities in the hidden layers of the network are modulated by gates, which are dynamically produced during training. The gates are outputs of networks themselves, trained with a sigmoid output activation. The regularization terms we have introduced correspond to properties exhibited by biological neuronal ensembles. The first term penalizes low gate sparsity, ensuring that only a specified fraction of the network is used. The second term ensures that previously learned gates are recalled when the network is presented with input from previously learned tasks. Finally, there is a regularization term responsible for ensuring that new tasks are encoded in gates that are as orthogonal as possible from previously used ones. We demonstrate the ability of this method to alleviate catastrophic forgetting on continual learning benchmarks. When the new regularization terms are included in the model along with Elastic Weight Consolidation (EWC) it achieves better performance on the benchmark `permuted MNIST' than with EWC alone. The benchmark `rotated MNIST' demonstrates how similar tasks recruit similar neurons to the artificial neuronal ensemble.Comment: 13 pages, 9 figure

A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function.

The integrin αIIbβ3 on resting platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. αIIbβ3 is known to interact with the general integrin-recognition motif RGD (arginine-glycine-aspartate) as well as the fibrinogen-specific γ-chain dodecapeptide; however, it is not known how fibrinogen binding triggers platelet activation. NGR (asparagine-glycine-arginine) is another integrin-recognition sequence present in fibrinogen and this study aims to determine if it plays a role in the interaction between fibrinogen and αIIbβ3. NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC50 of 175 µM but failed to inhibit the adhesion of activated platelets to fibrinogen (IC50\u3e 500 µM). Resting platelet adhesion to mutant fibrinogens lacking the NGR sequences was reduced compared to normal fibrinogen under both static and shear conditions (200 s⁻¹). However, pre-activated platelets were able to fully spread on all types of fibrinogen. Thus, the NGR motif in fibrinogen is the site that is primarily responsible for the interaction with resting αIIbβ3 and is responsible for triggering platelet activation

Police perceptions of problem-oriented policing and evidence-based policing: evidence from England and Wales

The history of policing is littered with reform programmes, which aim to improve effectiveness, efficiency and legitimacy. Problem-oriented policing (POP) and evidence-based policing (EBP) are two popular and enduring reform efforts, both of which have generated significant researcher and practitioner attention. There are important similarities between POP and EBP: both approaches provide a framework intended to improve the outcomes of policing. There are also key differences, however, in terms of their main objectives, standards of evidence and units of analysis. Despite both approaches being widely advocated and implemented, presently little is known about police practitioner understanding of the relationship between POP and EBP, both in principle and in practice. To address this gap, this paper draws on survey (n = 4,141) and interview (n = 86) data collected from 19 police forces in England and Wales in 2019 to explore police practitioners’ views on the relationship between POP and EBP, and the extent to which these two approaches inform contemporary police practices. Our findings indicate that respondents generally viewed the two approaches as complementary and important frameworks for orienting police work. However, respondents also drew attention to how the two approaches are not always connected organisationally nor in the minds of police personnel. In addition, challenges were identified in the application of both approaches in practice. Our results suggest that more needs to be done to maximise the potential of POP and EBP, both separately and synergistically. The article concludes by suggesting some ways in which this might be achieved

Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum

BACKGROUND: The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved. RESULTS: We reassessed the central carbon metabolism of P. falciparum asexual and sexual blood stages, by metabolically labeling each stage with (13)C-glucose and (13)C-glutamine, and analyzing isotopic enrichment in key pathways using mass spectrometry. In contrast to previous findings, we found that carbon skeletons derived from both glucose and glutamine are catabolized in a canonical oxidative TCA cycle in both the asexual and sexual blood stages. Flux of glucose carbon skeletons into the TCA cycle is low in the asexual blood stages, with glutamine providing most of the carbon skeletons, but increases dramatically in the gametocyte stages. Increased glucose catabolism in the gametocyte TCA cycle was associated with increased glucose uptake, suggesting that the energy requirements of this stage are high. Significantly, whereas chemical inhibition of the TCA cycle had little effect on the growth or viability of asexual stages, inhibition of the gametocyte TCA cycle led to arrested development and death. CONCLUSIONS: Our metabolomics approach has allowed us to revise current models of P. falciparum carbon metabolism. In particular, we found that both asexual and sexual blood stages utilize a conventional TCA cycle to catabolize glucose and glutamine. Gametocyte differentiation is associated with a programmed remodeling of central carbon metabolism that may be required for parasite survival either before or after uptake by the mosquito vector. The increased sensitivity of gametocyte stages to TCA-cycle inhibitors provides a potential target for transmission-blocking drugs

Building Relationships in Inclusive Research in Diverse Contexts

This article explores relationships between academics and people with intellectual disabilities collaborating in inclusive research. The authors present and reflect upon narrative accounts from Norway and England from both sides of the relationship. Each relationship is examined, including how it was initiated, established, developed and sustained, what worked well, what the obstacles were and how any conflicts were approached. The concept of being an ‘alongsider’, working alongside each other (and alongside participants with intellectual disabilities) is used. The paper shows variety in how alongsider relationships are initiated and fostered over time. Mostly, partnerships were initiated informally, based on pre-existing relationships as friends or through support worker-client relationship or earlier research cooperation, although one was initiated through a formal selection process. The paper concludes that when building relationships over time, the personal dimension is important, including sharing an interest, mutual respect and liking each other, while funding and tight timelines can interfere

Erythrocyte β spectrin can be genetically targeted to protect mice from malaria

The malaria parasite hijacks host erythrocytes to shield itself from the immune system and proliferate. Red blood cell abnormalities can provide protection from malaria by impeding parasite invasion and growth within the cell or by compromising the ability of parasites to avoid host clearance. Here, we describe 2 N-ethyl-N-nitrosourea–induced mouse lines, SptbMRI26194 and SptbMRI53426, containing single-point mutations in the erythrocyte membrane skeleton gene, b spectrin (Sptb), which exhibit microcytosis but retain a relatively normal ratio of erythrocyte surface area to volume and are highly resistant to rodent malaria. We propose the major factor responsible for malaria protection is the specific clearance of mutant erythrocytes, although an enhanced clearance of ninfected mutant erythrocytes was also observed (ie, the bystander effect). Using an in vivo erythrocyte tracking assay, we established that this phenomenon occurs irrespective of host environment, precluding the involvement of nonerythrocytic cells in the resistance mechanism. Furthermore, we recapitulated this phenotype by disrupting the interaction between ankyrin-1 and b spectrin in vivo using CRISPR/Cas9 genome editing technology, thereby genetically validating a potential antimalarial target. This study sheds new light on the role of b spectrin during Plasmodium infection and highlights how changes in the erythrocyte cytoskeleton can substantially influence malaria susceptibility with minimal adverse consequences for the host.This work was supported by the National Health and Medical Research Council (grants APP605524 , 4 90037 and 104 7082), the Australian Research Council (grants DP12010061 and FL150100106), the National Collaborative Research Infrastructure Strategy of Australia and the education investment fund from the Department of Innovation, Industry, Science and Research via the Australian Phenomics Network, and the Japan Society for the Promotion of Science Fellowship Program (grant S16706)