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Magnetic nanowires (MNWs) can have their moments reversed via several mechanisms that are controlled using the composition, length, diameter, and density of nanowires in arrays as-synthesized or as individual nanoparticles in assays or gels. This tailoring of magnetic reversal leads to unique properties that can be used as a signature for reading out the type of MNW for applications as nano-barcodes. When synthesized inside track-etched polycarbonate membranes, the resulting MNW-embedded membranes can be used as biocompatible bandaids for detection without contact or optical sighting. When etched out of the growth template, free-floating MNWs are internalized by cells at 37 °C such that cells and/or exosomes can be collected and detected. In applications of cryopreservation, MNWs can be suspended in cryopreservation agents (CPAs) for injection into the blood vessels of tissues and organs as they are vitrified to −200 °C. Using an alternating magnetic field, the MNWs can then be nanowarmed rapidly to prevent crystallization and uniformly to prevent cracking of specimens, for example, as grafts or transplants. This invited paper is a review of recent progress in the specific bioapplications of MNWs to barcodes, biocomposites, and nanowarmers. [ABSTRACT FROM AUTHOR]

Isolating tumor exosomes (TEX) secreted by cancer cells can provide valuable information about the state of a tumor. Here, we present a method to rapidly isolate TEX using magnetic nanowires (MNWs). Specifically, two sets of Fe/Au segmented MNWs were used to isolate TEX released by canine osteosarcoma cell lines (OSCA 8, 32, and 40). These MNWs were prepared by electrodeposition showcasing similar length (2.2(1) μm) and diameter (36(3) nm) but different Fe/Au segment thickness: 120(20)/30(6) nm (sample A) and 28(7)/3(1) nm (sample B). Magnetic measurements indicate that we can effectively tune the magnetic response of the MNWs by changing their segment thickness, obtaining a more anisotropic behavior for sample A. The internalization of these MNWs by OSCA cells as a function of their concentration has been followed by fluorescence microscopy, and a concentration around 25 μg of Fe/Au MNWs per 3 × 105 cells has been defined as optimal. Electron microscopy images have revealed that, once internalized, these MNWs end up residing within lysosomes inside the cancer cells, where they tend to be degraded (especially the Fe segments) and fragmented into smaller pieces. Lower degradation for sample B has been observed and related to differences in the synthesis/functionalization process of both samples. We have hypothesized that these fragments of Fe/Au MNWs are packaged into TEX released to the medium which can then be isolated via a magnetic stand. This has been tested by carrying out TEX isolation experiments on the OSCA cell and comparing the magnetically isolated TEX with those isolated by using conventional methods based on centrifugation. Nanoparticle tracking analysis (NanoSight) has confirmed that the TEX isolated with MNWs have a comparable size distribution and yield to those obtained by using conventional methods, indicating that our magnetic isolation method can consistently provide relatively high TEX yields in a low-cost and fast way. [ABSTRACT FROM AUTHOR]

A personal narrative is presented which explores the author's experience of being at Inauguration day for the forty fifth president of the U.S.

1. At the end of Book 12 of Paradise Lost, after viewing the highlights of Biblical history, Adam explains what he has learned: 'Henceforth I learn, that to obey is [...]

The decarboxylative nucleophilic addition reactions of malonic acid half thioesters (MAHTs) and malonic acid half oxyesters (MAHOs) with ketone and aldehyde electrophiles in the presence of stoichiometric or catalytic quantities of triethylamine at room temperature are described. The mechanistic insights gained through the studies could be employed in the development of a new decarboxylative coumarin synthesis.

Graphical abstract Highlights • A series of potent azaindazole inhibitors of LRRK2 was discovered. • A putative intramolecular hydrogen bond was crucial for LRRK2 potency. • Optimization led to potent, metabolically stable, and brain-permeable molecules. • Compound 18 showed excellent LRRK2 potency and properties. Abstract The discovery of disease-modifying therapies for Parkinson's Disease (PD) represents a critical need in neurodegenerative medicine. Genetic mutations in LRRK2 are risk factors for the development of PD, and some of these mutations have been linked to increased LRRK2 kinase activity and neuronal toxicity in cellular and animal models. As such, research towards brain-permeable kinase inhibitors of LRRK2 has received much attention. In the course of a program to identify structurally diverse inhibitors of LRRK2 kinase activity, a 5-azaindazole series was optimized for potency, metabolic stability and brain penetration. A key design element involved the incorporation of an intramolecular hydrogen bond to increase permeability and potency against LRRK2. This communication will outline the structure-activity relationships of this matched pair series including the challenge of obtaining a desirable balance between metabolic stability and brain penetration. [ABSTRACT FROM AUTHOR]

Usage of models integrating mediation and moderation is on the rise in the organizational sciences. While moderation and mediation are fairly well understood by themselves, additional complexities emerge when combining them. Some guidance exists regarding the empirical testing of such models, but this guidance is widely misunderstood. Furthermore, very little guidance exists regarding the theoretical justification of such models. This article offers a checklist of recommendations for the presentation, justification, and testing of models integrating mediation and moderation and compares these to what is actually being done via a review of empirical papers in top-tier journals. [ABSTRACT FROM AUTHOR]

Among all transition metals magnetic alloys, Co35Fe65 possesses the highest saturation magnetization BS = 2.45 T at room temperature given by the so-called "Slater-Pauling limit". For controlled electrodeposition of Co35Fe65 nanowire arrays the following parameters were found to be optimal: electrolyte solution with 1-2 mM malonic acid (MA), ionic ratio Fe+2/Co+2 = 2.0, growth rate, and pulsed potential deposition with time-on (2.5 s) at the potential of -1.15 V/SCE and time-off (1.0 s) at -0.70 V/SCE. These arrays were deposited inside anodic aluminum oxide (AAO) templates that contained columnar nanopores with diameters either 35 or 200 nm. Cyclic voltammetry was used in solution with and without MA and reaction mechanism was proposed to explain the critical role of MA in electrodeposition of CoFe alloys. In addition to uniform deposition of stechiometric Co35Fe65 alloys, a selectivity ratio, (SR) ~1.0, were achieved, which means that the atomic ratio of Fe/Co in the nanowire matched the molar ratio of Fe+2/Co+2 in the electrolyte. The magnetic behavior of the subsequent 2.45 T Co35Fe65 nanowire arrays showed that the shape and magnetostatic anisotropies dominated the effective anisotropy, and the impact of magnetocrystalline and magnetelastic anisotropies field was very small. [ABSTRACT FROM AUTHOR]

Electrodeposited Fe and Fe–Au nanowires were studied for potential as MRI contrast agents, especially for T2-weighted imaging. Transverse relaxivities up to r2 = 77.1 mM Fe−1 s−1 (at 1.5 T) were achieved when Fe–Au nanowires were coated with thiol and carboxylic acid functionalized poly(ethyleneglycol). T2-Weighted images (9 T) verified successful contrast. [ABSTRACT FROM AUTHOR]

In this paper we present a statistical method for inferring historical social networks from biographical documents as well as the scholarly aims for doing so. Existing scholarship on historical social networks is scattered across an unmanageable number of disparate books and articles. A researcher interested in how persons were connected to one another in our field of study, early modern Britain (c. 1500-1700), has no global, unified resource to which to turn. Manually building such a network is infeasible, since it would need to represent thousands of nodes and tens of millions of potential edges just to include the relations among the most prominent persons of the period. Our Six Degrees of Francis Bacon project takes up recent statistical techniques and digital tools to reconstruct and visualize the early modern social network. We describe in this paper the natural language processing tools and statistical graph learning techniques that we used to extract names and infer relations from the Oxford Dictionary of National Biography. We then explain the steps taken to test inferred relations against the knowledge of experts in order to improve the accuracy of the learning techniques. Our argument here is twofold: first, that the results of this process, a global visualization of Britain's early modern social network, will be useful to scholars and students of the period; second, that the pipeline we have developed can, with local modifications, be reused by other scholars to generate networks for other historical or contemporary societies from biographical documents. [ABSTRACT FROM AUTHOR]

Generally, computer security incident response team (CSIRT) managers and team members focus only on individual-level skills. The field of organizational psychology can contribute to an understanding of the full range of CSIRT job requirements, which include working as a team and within a larger multiteam system. [ABSTRACT FROM PUBLISHER]

Wehave recently reported a series of tetrahydroquinazoline (THQ)mTOR inhibitors that produced a clinical candidate 1(GDC-0349).Through insightful design, we hoped to discover and synthesize a newseries of small molecule inhibitors that could attenuate CYP3A4 time-dependentinhibition commonly observed with the THQ scaffold, maintain or improveaqueous solubility and oral absorption, reduce free drug clearance,and selectively increase mTOR potency. Through key in vitro and invivo studies, we demonstrate that a pyrimidoaminotropane based corewas able to address each of these goals. This effort culminated inthe discovery of 20(GNE-555), a highly potent, selective,metabolically stable, and efficacious mTOR inhibitor. [ABSTRACT FROM AUTHOR]