Particle Moment Canting in CoFe2O4 Nanoparticles

Polarization-analyzed small-angle neutron scattering methods are used to determine the spin morphology in high crystalline anisotropy, 11 nm diameter CoFe2O4 nanoparticle assemblies with randomly oriented easy axes. In moderate to high magnetic fields, the nanoparticles adopt a uniformly canted structure, rather than forming domains, shells, or other arrangements. The observed canting angles agree quantitatively with those predicted from an energy model dominated by Zeeman and anisotropy competition, with implications for the technological use of such nanoparticles

Spin canting across core/shell Fe3O4/MnxFe3−xO4 nanoparticles

Magnetic nanoparticles (MNPs) have become increasingly important in biomedical applications like magnetic imaging and hyperthermia based cancer treatment. Understanding their magnetic spin configurations is important for optimizing these applications. The measured magnetization of MNPs can be significantly lower than bulk counterparts, often due to canted spins. This has previously been presumed to be a surface effect, where reduced exchange allows spins closest to the nanoparticle surface to deviate locally from collinear structures. We demonstrate that intraparticle effects can induce spin canting throughout a MNP via the Dzyaloshinskii-Moriya interaction (DMI). We study ~7.4 nm diameter, core/shell Fe3O4/MnxFe3−xO4 MNPs with a 0.5 nm Mn-ferrite shell. Mössbauer spectroscopy, x-ray absorption spectroscopy and x-ray magnetic circular dichroism are used to determine chemical structure of core and shell. Polarized small angle neutron scattering shows parallel and perpendicular magnetic correlations, suggesting multiparticle coherent spin canting in an applied field. Atomistic simulations reveal the underlying mechanism of the observed spin canting. These show that strong DMI can lead to magnetic frustration within the shell and cause canting of the net particle moment. These results illuminate how core/shell nanoparticle systems can be engineered for spin canting across the whole of the particle, rather than solely at the surface

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Origin of Surface Canting within Fe3O4 Nanoparticles

The nature of near-surface spin canting within Fe3O4 nanoparticles is highly debated. Here we develop a neutron scattering asymmetry analysis which quantifies the canting angle to between 23° and 42° at 1.2 T. Simultaneously, an energy-balance model is presented which reproduces the experimentally observed evolution of shell thickness and canting angle between 10 and 300 K. The model is based on the concept of Td site reorientation and indicates that surface canting involves competition between magnetocrystalline, dipolar, exchange, and Zeeman energies

Developing online communication training to request donation for vascularized composite allotransplantation (VCA): improving performance to match new US organ donation targets

Abstract Background Approaching families of dying or newly deceased patients to donate organs requires specialized knowledge and a mastery of relational communication. As the transplantation field has progressed, Donation Professionals (DPs) are also leading conversations with family decision makers (FDMs) about the donation of uncommon anatomical gifts, such as face, hands, genitalia, referred to as Vascularized Composite Allotransplants (VCA) without much training or experience. To address the need for training, we adapted and beta tested an evidenced-based communication training program for donation discussions to VCA requests. The overarching goal of Communicating Effectively about Donation for Vascularized Composite Allotransplantation (CEaD-VCA) is to increase the number of VCA authorizations and to improve the socioemotional outcomes of FDMs. Methods We developed CEaD-VCA, an online, on-demand training program based on the previously tested, evidenced-based communication skills training program designed to train DPs to have conversations about solid organ donation. The training was modified utilizing data from a national telephone survey with DPs and results of 6 focus groups conducted with members of the general public. The survey and focus groups assessed knowledge, attitudes, and barriers to VCA donation. The training was shaped by a partnership with a leading industry partner, the Gift of Life Institute.™ Results Using the results as a guide, the existing CEaD training program, consisting of interactive eLearning modules, was adapted to include technical information about VCA, foundational communication skills, and two interactive example VCA donation request scenarios to facilitate active learning. Forty-two DPs from two partner Organ Procurement Organizations (OPOs) participated in the beta test of CEaD-VCA. Pre- and post-test surveys assessed the impact of the training. Conclusions The training was scored highly by DPs in effectiveness and ease of use. This project created a standardized, accessible, and comprehensive training for DPs to communicate about VCA donation. CEaD-VCA is an example of how to develop a communication skills training for difficult conversations utilizing input from stakeholders, guided by communication theory. It also demonstrates how gaps in communication skills during medical education can be filled utilizing advanced online Learning Management Systems. The training specifically addresses new CMS rules concerning OPO performance metrics

Optimization of Vibration Absorbers: A Graphical Method^ for Use on Idealized Systems With Restricted Damping

can be used on complex real-world problems. It can also provide additional insight into the physical behavior of a transient system. References 1 Aggarwal, T. C, and Hasz, J. R., "Designing Optimum Dampers Against Self-Excited Chatter," ASME Paper No. 68-WA/ Prod-25. 2 Bartel, D. L., Haug, E. J., and Rim, K., "The Optimum Design of Spatial Frames Using the Method of Constrained Steepest Descent With State Equations," to be published in Journal of Engineering for Industry, TRANS. ASME, Series B, Vol. 93, 1971. 3 Falcon, K. C, Stone, B. J., Simcock, W. D., anaSAndrew, C, "Optimization of Vibration Absorbers: A Graphical Method^ for Use on Idealized Systems With Restricted Damping," Journal of Mechanical Engineering Science, Vol. 9, No. 5, 1967, pp. 374-381. 4 The authors have presented two applications of an optimization program involving low order linear mechanical systems. The results are of some interest although the paper is hard to follow due to misprints (Figs. 1 and 4 seem to be interchanged) and unusual notation (s is called a state vector while z, a vector of displacements and velocities, though typically called a state vector in dynamics, is not called a state vector in the paper). The reference to "time domain optimization" in the title may be misleading. Another way to describe what the authors have done is by the phrase "parameter optimization" since the computer program apparently varied a damping parameter and a spring constant to optimize some aspects of the transient response of a particular 2 degree-of-freedom linear system model subject to inequality constraints. In related work, a group at I.I.T. investigated several possible methods of optimizing vibratory systems. Included were not only parameter optimization but also a true time domain optimization in which dynamic programming techniques were used to determine the optimal time history of forces which would achieve a minimum of a performance criterion subject to constraints, independent of the manner in which the force would actually be realized The authors have demonstrated their ability to achieve parameter optimization using a gradient technique, but it is not entirely clear that the method should be used on "complex realworld problems." The authors' examples are hardly complex nor do they necessarily represent the real world. Would anyone realistically construct a car bumper by trying to match it to a linear spring and dashpot combination? The potential of the technique might be better illustrated by using it to optimize nonlinear devices which, though suboptimal in the true time domain sense, yield responses closer to optimal than could be achieved with linear devices. Even in the vibration absorber problem, the proposed criterion of time-optimal energy dissipation is not so easy to justify. This criterion evidently yields a different optimal system for every different initial condition and indeed for every choice of percent energy remaining, t. This phenomenon might be explained by realizing that the response of the system in question can at least roughly be considered the sum of the responses of two normal modes. Each modal velocity is described 2 Professor and Graduate Student, respectively, Department of Mechanical Engineering, University of California, Davis, Calif. 3 Numbers in brackets designate Additional References at end of discussion. by an exponentially decaying sinusoid whose initial value is a function of all initial conditions. The rate of exponential decay for each mode can be different functions of the design parameters. For e ->-1 the tradeoff between the fast decay of a mode with high initial conditions and the slow decay of the mode with lower initial conditions is very critical. In the extreme one could hypothesize the mode with large initial value decaying very rapidly and the low initial condition mode never decaying in order for values of 6 close to one to be achieved in optimum time. The exact nature of the trade off is a function of initial conditions and e. When e ->-0, the responses of both modes are forced to be small as soon as possible. When t-*T for this case, the difference due to initial conditions in the values of the modal responses must be small because the responses are small. Hence, initial conditions have little effect, and the main concern of the optimization process becomes making both responses small as soon as possible. This is the most reasonable criteria for optimization. Surely for most vibration absorber design techniques one desires a useful criterion which will produce a single isolation design which is optimal for a broad class of inputs or initial conditions. The authors' results for e ->• 0 suggest the sort of result in optimal linear regulator design in which an infinite time integral square criteria yields an optimal design independent of initial conditions. Finally, the paper illustrates the difficulties in interpretation which often arise in parameter optimization. Computed optimal parameters may be nearly useless unless supplemented by an understanding of the influence of small changes in the optimization criterion on the system parameters. In equation In another instance, the authors have taken a specific result and made a rather broad generalization from it which may not be justified. The statement that "an optimum steady state absorber will also be nearly optimum for transient conditions when e is small" surely must be qualified. Though the statement is true for the authors' specific case, many other constraints and criteria might be used, and it would be amazing if the statement were universally true. Only when the systems remain entirely in the domain of linear optimum systems can one expect simple relations between optimal systems designed on the basis of transient and forced response [3]

Stat5 is critical for the development and maintenance of myeloproliferative neoplasm initiated by Nf1 deficiency

Juvenile myelomonocytic leukemia is a rare myeloproliferative neoplasm characterized by hyperactive RAS signaling. Neurofibromin1 (encoded by the NF1 gene) is a negative regulator of RAS activation. Patients with neurofibromatosis type 1 harbor loss-of-function mutations in NF1 and have a 200- to 500-fold increased risk of juvenile myelomonocytic leukemia. Leukemia cells from patients with juvenile myelomonocytic leukemia display hypersensitivity to certain cytokines, such as granulocyte-macrophage colony-stimulating factor. The granulocyte-macrophage colony-stimulating factor receptor utilizes pre-associated JAK2 to initiate signals after ligand binding. JAK2 subsequently activates STAT5, among other downstream effectors. Although STAT5 is gaining recognition as an important mediator of growth factor signaling in myeloid leukemias, the contribution of STAT5 to the development of hyperactive RAS-initiated myeloproliferative disease has not been well described. In this study, we investigated the consequence of STAT5 attenuation via genetic and pharmacological approaches in Nf1-deficient murine models of juvenile myelomonocytic leukemia. We found that homozygous Stat5 deficiency extended the lifespan of Nf1-deficient mice and eliminated the development of myeloproliferative neoplasm associated with Nf1 gene loss. Likewise, we found that JAK inhibition with ruxolitinib attenuated myeloproliferative neoplasm in Nf1-deficient mice. Finally, we found that primary cells from a patient with KRAS-mutant juvenile myelomonocytic leukemia displayed reduced colony formation in response to JAK2 inhibition. Our findings establish a central role for STAT5 activation in the pathogenesis of juvenile myelomonocytic leukemia and suggest that targeting this pathway may be of clinical utility in these patients

The SHELTER Trial of Transplanting Hepatitis C Virus–Infected Lungs Into Uninfected Recipients

SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA + donors and none have reported quality of life (QOL)