Near-field coupling of gold plasmonic antennas for sub-100 nm magneto-thermal microscopy

The development of spintronic technology with increasingly dense, high-speed, and complex devices will be accelerated by accessible microscopy techniques capable of probing magnetic phenomena on picosecond time scales and at deeply sub-micron length scales. A recently developed time-resolved magneto-thermal microscope provides a path towards this goal if it is augmented with a picosecond, nanoscale heat source. We theoretically study adiabatic nanofocusing and near-field heat induction using conical gold plasmonic antennas to generate sub-100 nm thermal gradients for time-resolved magneto-thermal imaging. Finite element calculations of antenna-sample interactions reveal focused electromagnetic loss profiles that are either peaked directly under the antenna or are annular, depending on the sample's conductivity, the antenna's apex radius, and the tip-sample separation. We find that the thermal gradient is confined to 40 nm to 60 nm full width at half maximum for realistic ranges of sample conductivity and apex radius. To mitigate this variation, which is undesirable for microscopy, we investigate the use of a platinum capping layer on top of the sample as a thermal transduction layer to produce heat uniformly across different sample materials. After determining the optimal capping layer thickness, we simulate the evolution of the thermal gradient in the underlying sample layer, and find that the temporal width is below 10 ps. These results lay a theoretical foundation for nanoscale, time-resolved magneto-thermal imaging.Comment: 24 pages including Supporting Information, 6 figures in the main text, 4 supporting figure

Magnetization states and switching in narrow-gapped ferromagnetic nanorings

We study permalloy nanorings that are lithographically fabricated with narrow gaps that break the rotational symmetry of the ring while retaining the vortex ground state, using both micromagnetic simulations and magnetic force microscopy (MFM). The vortex chirality in these structures can be readily set with an in-plane magnetic field and easily probed by MFM due to the field associated with the gap, suggesting such rings for possible applications in storage technologies. We find that the gapped ring edge characteristics (i.e., edge profile and gap shape) are critical in determining the magnetization switching field, thus elucidating an essential parameter in the controls of devices that might incorporate such structures

Nanoscale magnetization and current imaging using scanning-probe magneto-thermal microscopy

Magnetic microscopy that combines nanoscale spatial resolution with picosecond scale temporal resolution uniquely enables direct observation of the spatiotemporal magnetic phenomena that are relevant to future high-speed, high-density magnetic storage and logic technologies. Magnetic microscopes that combine these metrics has been limited to facility-level instruments. To address this gap in lab-accessible spatiotemporal imaging, we develop a time-resolved near-field magnetic microscope based on magneto-thermal interactions. We demonstrate both magnetization and current density imaging modalities, each with spatial resolution that far surpasses the optical diffraction limit. In addition, we study the near-field and time-resolved characteristics of our signal and find that our instrument possesses a spatial resolution on the scale of 100 nm and a temporal resolution below 100 ps. Our results demonstrate an accessible and comparatively low-cost approach to nanoscale spatiotemporal magnetic microscopy in a table-top form to aid the science and technology of dynamic magnetic devices with complex spin textures

Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis

Virulence-linked pathways in opportunistic pathogens are putative therapeutic targets that may be associated with less potential for resistance than targets in growth-essential pathways. However, efficacy of virulence-linked targets may be affected by the contribution of virulence-related genes to metabolism. We evaluate the complex interrelationships between growth and virulence-linked pathways using a genome-scale metabolic network reconstruction of Pseudomonas aeruginosa strain PA14 and an updated, expanded reconstruction of P. aeruginosa strain PAO1. The PA14 reconstruction accounts for the activity of 112 virulence-linked genes and virulence factor synthesis pathways that produce 17 unique compounds. We integrate eight published genome-scale mutant screens to validate gene essentiality predictions in rich media, contextualize intra-screen discrepancies and evaluate virulence-linked gene distribution across essentiality datasets. Computational screening further elucidates interconnectivity between inhibition of virulence factor synthesis and growth. Successful validation of selected gene perturbations using PA14 transposon mutants demonstrates the utility of model-driven screening of therapeutic targets

Defining Global Neuroendocrine Gene Expression Patterns Associated with Reproductive Seasonality in Fish

Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays.Using both theoretical and experimental strategies, we report for the first time global gene expression patterns throughout a breeding season which may account for dynamic neuroendocrine regulation of seasonal reproductive development

Ipilimumab administration for advanced melanoma in patients with pre-existing Hepatitis B or C infection: a multicenter, retrospective case series

Ipilimumab is a fully human, monoclonal antibody directed against Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) that has demonstrated a survival benefit and durable disease control in patients with advanced melanoma. Ipilimumab is associated with potentially serious immune-related adverse events, including autoimmune hepatitis. Because clinical trials of ipilimumab excluded patients with pre-existing hepatitis B or C infection, there is a paucity of data on the safety of ipilimumab administration to that patient population. Here, we report the largest case series to date of patients with hepatitis B or C who received ipilimumab for advanced melanoma. Two of the nine patients described in this case series experienced fluctuations in their liver function tests (LFTs) and were subsequently treated with corticosteroids. Although this is a small series, the rate of hepatotoxicity appears similar to what has been seen in the general population treated with ipilimumab, and the ability to administer ipilimumab did not appear to be affected by concomitant hepatitis B or C infection. The use of ipilimumab in patients with metastatic melanoma who have pre-existing hepatitis can be considered among other therapeutic options

Coherent correlation imaging for resolving fluctuating states of matter

Fluctuations and stochastic transitions are ubiquitous in nanometre-scale systems, especially in the presence of disorder. However, their direct observation has so far been impeded by a seemingly fundamental, signal-limited compromise between spatial and temporal resolution. Here we develop coherent correlation imaging (CCI) to overcome this dilemma. Our method begins by classifying recorded camera frames in Fourier space. Contrast and spatial resolution emerge by averaging selectively over same-state frames. Temporal resolution down to the acquisition time of a single frame arises independently from an exceptionally low misclassification rate, which we achieve by combining a correlation-based similarity metric1,2 with a modified, iterative hierarchical clustering algorithm3,4. We apply CCI to study previously inaccessible magnetic fluctuations in a highly degenerate magnetic stripe domain state with nanometre-scale resolution. We uncover an intricate network of transitions between more than 30 discrete states. Our spatiotemporal data enable us to reconstruct the pinning energy landscape and to thereby explain the dynamics observed on a microscopic level. CCI massively expands the potential of emerging high-coherence X-ray sources and paves the way for addressing large fundamental questions such as the contribution of pinning5–8 and topology9–12 in phase transitions and the role of spin and charge order fluctuations in high-temperature superconductivity13,14

Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains

Background Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify mechanisms responsible for adaptation during bronchiectasis infections, a bronchiectasis isolate, PAHM4, was phenotypically and genotypically characterized. Results This strain displays phenotypes that have been associated with chronic respiratory infections in CF including alginate over-production, rough lipopolysaccharide, quorum-sensing deficiency, loss of motility, decreased protease secretion, and hypermutation. Hypermutation is a key adaptation of this bacterium during the course of chronic respiratory infections and analysis indicates that PAHM4 encodes a mutated mutS gene responsible for a ~1,000-fold increase in mutation rate compared to wild-type laboratory strain P. aeruginosa PAO1. Antibiotic resistance profiles and sequence data indicate that this strain acquired numerous mutations associated with increased resistance levels to β-lactams, aminoglycosides, and fluoroquinolones when compared to PAO1. Sequencing of PAHM4 revealed a 6.38 Mbp genome, 5.9 % of which were unrecognized in previously reported P. aeruginosa genome sequences. Transcriptome analysis suggests a general down-regulation of virulence factors, while metabolism of amino acids and lipids is up-regulated when compared to PAO1 and metabolic modeling identified further potential differences between PAO1 and PAHM4. Conclusions This work provides insights into the potential differential adaptation of this bacterium to the lung of patients with bronchiectasis compared to other clinical settings such as cystic fibrosis, findings that should aid the development of disease-appropriate treatment strategies for P. aeruginosa infections