CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging

MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these ‘smart’ self-assembling nanomaterials

XMM-Newton X-ray study of early type stars in the Carina OB1 association

<p><b>Aims:</b> X-ray properties of the stellar population in the Carina OB1 association are examined with special emphasis on early-type stars. Their spectral characteristics provide some clues to understanding the nature of X-ray formation mechanisms in the winds of single and binary early-type stars.</p> <p><b>Methods:</b> A timing and spectral analysis of five observations with XMM-Newton is performed using various statistical tests and thermal spectral models.</p> <p><b>Results:</b> 235 point sources have been detected within the field of view. Several of these sources are probably pre-main sequence stars with characteristic short-term variability. Seven sources are possible background AGNs. Spectral analysis of twenty four sources of type OB and WR 25 was performed. We derived spectral parameters of the sources and their fluxes in three energy bands. Estimating the interstellar absorption for every source and the distance to the nebula, we derived X-ray luminosities of these stars and compared them to their bolometric luminosities. We discuss possible reasons for the fact that, on average, the observed X-ray properties of binary and single early type stars are not very different, and give several possible explanations.</p&gt

Slogging and Stumbling Toward Social Justice in a Private Elementary School: The Complicated Case of St. Malachy

This case study examines St. Malachy, an urban Catholic elementary school primarily serving children traditionally marginalized by race, class, linguistic heritage, and disability. As a private school, St. Malachy serves the public good by recruiting and retaining such traditionally marginalized students. As empirical studies involving Catholic schools frequently juxtapose them with public schools, the author presents this examination from a different tack. Neither vilifying nor glorifying Catholic schooling, this study critically examines the pursuit of social justice in this school context. Data gathered through a 1-year study show that formal and informal leaders in St. Malachy adapted their governance, aggressively sought community resources, and focused their professional development to build the capacity to serve their increasingly pluralistic student population. The analysis confirms the deepening realization that striving toward social justice is a messy, contradictory, and complicated pursuit, and that schools in both public and private sectors are allies in this pursuit

Multi-dimensional modelling of X-ray spectra for AGN accretion-disk outflows III: application to a hydrodynamical simulation

We perform multi-dimensional radiative transfer simulations to compute spectra for a hydrodynamical simulation of a line-driven accretion disk wind from an active galactic nucleus. The synthetic spectra confirm expectations from parameterized models that a disk wind can imprint a wide variety of spectroscopic signatures including narrow absorption lines, broad emission lines and a Compton hump. The formation of these features is complex with contributions originating from many of the different structures present in the hydrodynamical simulation. In particular, spectral features are shaped both by gas in a successfully launched outflow and in complex flows where material is lifted out of the disk plane but ultimately falls back. We also confirm that the strong Fe Kalpha line can develop a weak, red-skewed line wing as a result of Compton scattering in the outflow. In addition, we demonstrate that X-ray radiation scattered and reprocessed in the flow has a pivotal part in both the spectrum formation and determining the ionization conditions in the wind. We find that scattered radiation is rather effective in ionizing gas which is shielded from direct irradiation from the central source. This effect likely makes the successful launching of a massive disk wind somewhat more challenging and should be considered in future wind simulations.Comment: 14 pages, 8 figures. Accepted for publication by MNRA

Governance considerations for seeker–solver relationships: a knowledge‐based perspective in crowdsourcing for innovation contests

The need to solve innovation problems and insource knowledge has led to an increasing number of organizations engaging in crowdsourcing activities and subsequently establishing working relationships with winning solution providers. Using a knowledge‐based view and the problem‐solving perspective, we develop a theoretical framework suggesting how specific innovation problem attributes (i.e. the decomposability, formulation and search space of the problem) influence the governance decision (unilateral vs. bilateral) of seekers to manage the relationship with winning solvers. We empirically analyse the framework using 582 challenges broadcast on the NineSigma crowdsourcing platform. Our results indicate that problem attributes – the formulation and search space of the problem – have a positive effect on seekers’ preference towards unilateral governance structures. However, we did not find any empirical confirmation of the effect that the decomposability of the innovation problem has on seekers’ preference towards unilateral governance structures. This study offers several contributions to the crowdsourcing literature, and also has important implications for managers of organizations aiming to insource knowledge through crowdsourcing for innovation contests

Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity

Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML

Effect of probe characteristics on the subtractive hybridization efficiency of human genomic DNA

<p>Abstract</p> <p>Background</p> <p>The detection sensitivity of low abundance pathogenic species by polymerase chain reaction (PCR) can be significantly enhanced by removing host nucleic acids. This selective removal can be performed using a magnetic bead-based solid phase with covalently immobilized capture probes. One of the requirements to attain efficient host background nucleic acids subtraction is the capture probe characteristics.</p> <p>Findings</p> <p>In this study we investigate how various capture probe characteristics influence the subtraction efficiency. While the primary focus of this report is the impact of probe length, we also studied the impact of probe conformation as well as the amount of capture probe attached to the solid phase. The probes were immobilized on magnetic microbeads functionalized with a phosphorous dendrimer. The subtraction efficiency was assessed by quantitative real time PCR using a single-step capture protocol and genomic DNA as target. Our results indicate that short probes (100 to 200 bp) exhibit the best subtraction efficiency. Additionally, higher subtraction efficiencies with these probes were obtained as the amount of probe immobilized on the solid phase decreased. Under optimal probes condition, our protocol showed a 90 - 95% subtraction efficiency of human genomic DNA.</p> <p>Conclusions</p> <p>The characteristics of the capture probe are important for the design of efficient solid phases. The length, conformation and abundance of the probes determine the capture efficiency of the solid phase.</p

Spin-current induced electric field

We theoretically predict that a pure steady state spin-current without charge-current can induce an electric field. A formula for the induced electric field is derived and we investigate its characteristics. Conversely, a moving spin is affected by an external electric field and we present a formula for the interaction energy.Comment: 4 pages, 2 figure

Do Social Bonds Matter for Emerging Adults?

The extent to which social bonds and turning points influence criminal activity has been the focus of much empirical research. However, there have been few empirical studies exploring social bonds and turning points and offending for those who have experienced emerging adulthood, a recently identified stage of the life course. Using data from the National Longitudinal Study of Adolescent Health we examined if indicators of social bonds and turning points were predictors of criminal offending. Several of the turning points and social bonds included in these analyses were found to influence decreases in criminal offending for a cohort of emerging adults. We extend previous research by examining the influence of social bonds and turning points on patterns of criminal offending during emerging adulthood

Curbside Recycling in the U.S.a.: Convenience and Mandatory Participation

This research examines the relationship between the success of a residential curbside recycling program (RCRP), measured as material recovery rate (MRR), and two program factors: (1) whether or not participation is mandated; and (2) convenience, measured by container provision, collection frequency and collection day relative to municipal solid waste collection day. Residential curbside recycling programs, with correct strategies and program design, can be an important part of solid waste management plans world-wide. While residential curbside recycling programs are growing in popularity, many basic design questions lie unanswered and successful program strategies are not always obvious. Data from 357 residential curbside recycling programs in the United States are used to test the hypotheses. Mandatory participation residential curbside recycling programs are seen to collect more material than voluntary participation residential curbside recycling programs. Container provision appears effective for voluntary, but not mandatory, residential curbside recycling programs. Increasing collection frequency appears to have a small positive effect on residential curbside recycling program success, while collection day has little effect on material recovery rate.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline