Ferromagnetic resonance of patterned chromium dioxide thin films grown by selective area chemical vapour deposition

This is the final version of the article. Available from the American Institute of Physics via the DOI in this record.A selective area chemical vapour deposition technique has been used to fabricate continuous and patterned epitaxial CrO2 thin films on (100)-oriented TiO2 substrates. Precessional magnetization dynamics were stimulated both electrically and optically, and probed by means of time-resolved Kerr microscopy and vector network analyser ferromagnetic resonance techniques. The dependence of the precession frequency and the effective damping parameter upon the static applied magnetic field were investigated. All films exhibited a large in-plane uniaxial anisotropy. The effective damping parameter was found to exhibit strong field dependence in the vicinity of the hard axis saturation field. However, continuous and patterned films were found to possess generally similar dynamic properties, confirming the suitability of the deposition technique for fabrication of future spintronic devices

Current-induced picosecond magnetization dynamics in a Ta/CoFeB/MgO Hall Bar (article)

This is the final version. Available on open access from IOP Publishing via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.1443Time-resolved Kerr microscopy (TRSKM) has been used to explore the small amplitude picosecond magnetization dynamics induced by spin-orbit torques in a Ta(4 nm)/Co40Fe40B20(1 nm)/MgO(1.6 nm)/Ta(1 nm) Hall bar structure. The time dependent polar magneto optical Kerr e ect was recorded following injection of a current pulse of 70 ps duration. Macrospin simulations provide a reasonable description of the precession and a transient background response as the eld strength and current polarity are varied, while con rming that the in-plane spin-orbit torque is dominant within this system. Increasing the current density within the simulations leads to coherent magnetization reversal. Inclusion of a modest in-plane bias eld is found to reduce both the switching current and the time required for switching. The orientation of the in-plane eld relative to the direction of the current determines whether the magnetization can be switched backwards and forwards by current pulses of the same or opposite polarity.Engineering and Physical Sciences Research Council (EPSRC

A Comparison of Machine Learning Methods for Cross-Domain Few-Shot Learning

We present an empirical evaluation of machine learning algorithms in cross-domain few-shot learning based on a fixed pre-trained feature extractor. Experiments were performed in five target domains (CropDisease, EuroSAT, Food101, ISIC and ChestX) and using two feature extractors: a ResNet10 model trained on a subset of ImageNet known as miniImageNet and a ResNet152 model trained on the ILSVRC 2012 subset of ImageNet. Commonly used machine learning algorithms including logistic regression, support vector machines, random forests, nearest neighbour classification, naïve Bayes, and linear and quadratic discriminant analysis were evaluated on the extracted feature vectors. We also evaluated classification accuracy when subjecting the feature vectors to normalisation using p-norms. Algorithms originally developed for the classification of gene expression data—the nearest shrunken centroid algorithm and LDA ensembles obtained with random projections—were also included in the experiments, in addition to a cosine similarity classifier that has recently proved popular in few-shot learning. The results enable us to identify algorithms, normalisation methods and pre-trained feature extractors that perform well in cross-domain few-shot learning. We show that the cosine similarity classifier and ℓ² -regularised 1-vs-rest logistic regression are generally the best-performing algorithms. We also show that algorithms such as LDA yield consistently higher accuracy when applied to ℓ² -normalised feature vectors. In addition, all classifiers generally perform better when extracting feature vectors using the ResNet152 model instead of the ResNet10 model

Mechanism of 150-cavity formation in influenza neuraminidase

The recently discovered 150-cavity in the active site of group-1 influenza A neuraminidase (NA) proteins provides a target for rational structure-based drug development to counter the increasing frequency of antiviral resistance in influenza. Surprisingly, the 2009 H1N1 pandemic virus (09N1) neuramidase was crystalized without the 150-cavity characteristic of group-1 NAs. Here we demonstrate, through a total sum of 1.6 μs of biophysical simulations, that 09N1 NA exists in solution preferentially with an open 150-cavity. Comparison with simulations using avian N1, human N2 and 09N1 with a I149V mutation and an extensive bioinformatics analysis suggests that the conservation of a key salt bridge is crucial in the stabilization of the 150-cavity across both subtypes. This result provides an atomic-level structural understanding of the recent finding that antiviral compounds designed to take advantage of contacts in the 150-cavity can inactivate both 2009 H1N1 pandemic and avian H5N1 viruses

The Influence of Polymer Purification on Photovoltaic Device Performance of a Series of Indacenodithiophene Donor Polymers

A series of low bandgap indacenodithiophene polymers is purified by recycling SEC in order to isolate narrow polydispersity fractions. This additional purification step is found to have a significant beneficial influence on the solar cell performance and the reasons for this performance increase are investigated

Comparison of imputation methods for handling missing covariate data when fitting a Cox proportional hazards model: a resampling study

<p>Abstract</p> <p>Background</p> <p>The appropriate handling of missing covariate data in prognostic modelling studies is yet to be conclusively determined. A resampling study was performed to investigate the effects of different missing data methods on the performance of a prognostic model.</p> <p>Methods</p> <p>Observed data for 1000 cases were sampled with replacement from a large complete dataset of 7507 patients to obtain 500 replications. Five levels of missingness (ranging from 5% to 75%) were imposed on three covariates using a missing at random (MAR) mechanism. Five missing data methods were applied; a) complete case analysis (CC) b) single imputation using regression switching with predictive mean matching (SI), c) multiple imputation using regression switching imputation, d) multiple imputation using regression switching with predictive mean matching (MICE-PMM) and e) multiple imputation using flexible additive imputation models. A Cox proportional hazards model was fitted to each dataset and estimates for the regression coefficients and model performance measures obtained.</p> <p>Results</p> <p>CC produced biased regression coefficient estimates and inflated standard errors (SEs) with 25% or more missingness. The underestimated SE after SI resulted in poor coverage with 25% or more missingness. Of the MI approaches investigated, MI using MICE-PMM produced the least biased estimates and better model performance measures. However, this MI approach still produced biased regression coefficient estimates with 75% missingness.</p> <p>Conclusions</p> <p>Very few differences were seen between the results from all missing data approaches with 5% missingness. However, performing MI using MICE-PMM may be the preferred missing data approach for handling between 10% and 50% MAR missingness.</p

IRE1/bZIP60-Mediated Unfolded Protein Response Plays Distinct Roles in Plant Immunity and Abiotic Stress Responses

Endoplasmic reticulum (ER)-mediated protein secretion and quality control have been shown to play an important role in immune responses in both animals and plants. In mammals, the ER membrane-located IRE1 kinase/endoribonuclease, a key regulator of unfolded protein response (UPR), is required for plasma cell development to accommodate massive secretion of immunoglobulins. Plant cells can secrete the so-called pathogenesis-related (PR) proteins with antimicrobial activities upon pathogen challenge. However, whether IRE1 plays any role in plant immunity is not known. Arabidopsis thaliana has two copies of IRE1, IRE1a and IRE1b. Here, we show that both IRE1a and IRE1b are transcriptionally induced during chemically-induced ER stress, bacterial pathogen infection and treatment with the immune signal salicylic acid (SA). However, we found that IRE1a plays a predominant role in the secretion of PR proteins upon SA treatment. Consequently, the ire1a mutant plants show enhanced susceptibility to a bacterial pathogen and are deficient in establishing systemic acquired resistance (SAR), whereas ire1b is unaffected in these responses. We further demonstrate that the immune deficiency in ire1a is due to a defect in SA- and pathogen-triggered, IRE1-mediated cytoplasmic splicing of the bZIP60 mRNA, which encodes a transcription factor involved in the expression of UPR-responsive genes. Consistently, IRE1a is preferentially required for bZIP60 splicing upon pathogen infection, while IRE1b plays a major role in bZIP60 processing upon Tunicamycin (Tm)-induced stress. We also show that SA-dependent induction of UPR-responsive genes is altered in the bzip60 mutant resulting in a moderate susceptibility to a bacterial pathogen. These results indicate that the IRE1/bZIP60 branch of UPR is a part of the plant response to pathogens for which the two Arabidopsis IRE1 isoforms play only partially overlapping roles and that IRE1 has both bZIP60-dependent and bZIP60-independent functions in plant immunity

Identification of Roles for Peptide: N-Glycanase and Endo-β-N-Acetylglucosaminidase (Engase1p) during Protein N-Glycosylation in Human HepG2 Cells

BACKGROUND: During mammalian protein N-glycosylation, 20% of all dolichol-linked oligosaccharides (LLO) appear as free oligosaccharides (fOS) bearing the di-N-acetylchitobiose (fOSGN2), or a single N-acetylglucosamine (fOSGN), moiety at their reducing termini. After sequential trimming by cytosolic endo beta-N-acetylglucosaminidase (ENGase) and Man2c1 mannosidase, cytosolic fOS are transported into lysosomes. Why mammalian cells generate such large quantities of fOS remains unexplored, but fOSGN2 could be liberated from LLO by oligosaccharyltransferase, or from glycoproteins by NGLY1-encoded Peptide-N-Glycanase (PNGase). Also, in addition to converting fOSGN2 to fOSGN, the ENGASE-encoded cytosolic ENGase of poorly defined function could potentially deglycosylate glycoproteins. Here, the roles of Ngly1p and Engase1p during fOS metabolism were investigated in HepG2 cells. METHODS/PRINCIPAL FINDINGS: During metabolic radiolabeling and chase incubations, RNAi-mediated Engase1p down regulation delays fOSGN2-to-fOSGN conversion, and it is shown that Engase1p and Man2c1p are necessary for efficient clearance of cytosolic fOS into lysosomes. Saccharomyces cerevisiae does not possess ENGase activity and expression of human Engase1p in the png1Delta deletion mutant, in which fOS are reduced by over 98%, partially restored fOS generation. In metabolically radiolabeled HepG2 cells evidence was obtained for a small but significant Engase1p-mediated generation of fOS in 1 h chase but not 30 min pulse incubations. Ngly1p down regulation revealed an Ngly1p-independent fOSGN2 pool comprising mainly Man(8)GlcNAc(2), corresponding to approximately 70% of total fOS, and an Ngly1p-dependent fOSGN2 pool enriched in Glc(1)Man(9)GlcNAc(2) and Man(9)GlcNAc(2) that corresponds to approximately 30% of total fOS. CONCLUSIONS/SIGNIFICANCE: As the generation of the bulk of fOS is unaffected by co-down regulation of Ngly1p and Engase1p, alternative quantitatively important mechanisms must underlie the liberation of these fOS from either LLO or glycoproteins during protein N-glycosylation. The fully mannosylated structures that occur in the Ngly1p-dependent fOSGN2 pool indicate an ERAD process that does not require N-glycan trimming

Structural and Functional Analysis of Laninamivir and its Octanoate Prodrug Reveals Group Specific Mechanisms for Influenza NA Inhibition

The 2009 H1N1 influenza pandemic (pH1N1) led to record sales of neuraminidase (NA) inhibitors, which has contributed significantly to the recent increase in oseltamivir-resistant viruses. Therefore, development and careful evaluation of novel NA inhibitors is of great interest. Recently, a highly potent NA inhibitor, laninamivir, has been approved for use in Japan. Laninamivir is effective using a single inhaled dose via its octanoate prodrug (CS-8958) and has been demonstrated to be effective against oseltamivir-resistant NA in vitro. However, effectiveness of laninamivir octanoate prodrug against oseltamivir-resistant influenza infection in adults has not been demonstrated. NA is classified into 2 groups based upon phylogenetic analysis and it is becoming clear that each group has some distinct structural features. Recently, we found that pH1N1 N1 NA (p09N1) is an atypical group 1 NA with some group 2-like features in its active site (lack of a 150-cavity). Furthermore, it has been reported that certain oseltamivir-resistant substitutions in the NA active site are group 1 specific. In order to comprehensively evaluate the effectiveness of laninamivir, we utilized recombinant N5 (typical group 1), p09N1 (atypical group 1) and N2 from the 1957 pandemic H2N2 (p57N2) (typical group 2) to carry out in vitro inhibition assays. We found that laninamivir and its octanoate prodrug display group specific preferences to different influenza NAs and provide the structural basis of their specific action based upon their novel complex crystal structures. Our results indicate that laninamivir and zanamivir are more effective against group 1 NA with a 150-cavity than group 2 NA with no 150-cavity. Furthermore, we have found that the laninamivir octanoate prodrug has a unique binding mode in p09N1 that is different from that of group 2 p57N2, but with some similarities to NA-oseltamivir binding, which provides additional insight into group specific differences of oseltamivir binding and resistance

Blood Parasites in Owls with Conservation Implications for the Spotted Owl (Strix occidentalis)

The three subspecies of Spotted Owl (Northern, Strix occidentalis caurina; California, S. o. occidentalis; and Mexican, S. o. lucida) are all threatened by habitat loss and range expansion of the Barred Owl (S. varia). An unaddressed threat is whether Barred Owls could be a source of novel strains of disease such as avian malaria (Plasmodium spp.) or other blood parasites potentially harmful for Spotted Owls. Although Barred Owls commonly harbor Plasmodium infections, these parasites have not been documented in the Spotted Owl. We screened 111 Spotted Owls, 44 Barred Owls, and 387 owls of nine other species for haemosporidian parasites (Leucocytozoon, Plasmodium, and Haemoproteus spp.). California Spotted Owls had the greatest number of simultaneous multi-species infections (44%). Additionally, sequencing results revealed that the Northern and California Spotted Owl subspecies together had the highest number of Leucocytozoon parasite lineages (n = 17) and unique lineages (n = 12). This high level of sequence diversity is significant because only one Leucocytozoon species (L. danilewskyi) has been accepted as valid among all owls, suggesting that L. danilewskyi is a cryptic species. Furthermore, a Plasmodium parasite was documented in a Northern Spotted Owl for the first time. West Coast Barred Owls had a lower prevalence of infection (15%) when compared to sympatric Spotted Owls (S. o. caurina 52%, S. o. occidentalis 79%) and Barred Owls from the historic range (61%). Consequently, Barred Owls on the West Coast may have a competitive advantage over the potentially immune compromised Spotted Owls