Structure and Function of Iron-Loaded Synthetic Melanin

We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure 12property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions. This study provides a detailed understanding of this complex class of synthetic biomaterials and gives insight into interactions and structures prevalent in naturally occurring melanins

Feature-interaction detection based on feature-based specifications

A Gd3+-coordinated polymerizable analogue of the MRI contrast agent Gd-DOTA was used to prepare amphiphilic block copolymers, with hydrophilic blocks composed entirely of the polymerized contrast agent. The resulting amphiphilic block copolymers assemble into nanoparticles (NPs) of spherical- or fibril-shape, each demonstrating enhanced relaxivity over Gd-DOTA. As an initial examination of their behavior in vivo, intraperitoneal (IP) injection of NPs into live mice was performed, showing long IP residence times, observed by MRI. Extended residence times for particles of well-defined morphology may represent a valuable design paradigm for treatment or diagnosis of peritoneal malignances

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Machine-Learning Accelerated First-Principles Accurate Modeling of the Solid–Liquid Phase Transition in MgO under Mantle Conditions

While accurate measurements of MgO under extreme high-pressure conditions are needed to understand and model planetary behavior, these studies are challenging from both experimental and computational modeling perspectives. Herein, we accelerate density functional theory (DFT) accurate calculations using deep neural network potentials (DNPs) trained over multiple phases and study the melting behavior of MgO via the two-phase coexistence (TPC) approach at 0–300 GPa and ≤9600 K. The resulting DNP–TPC melting curve is in excellent agreement with existing experimental studies. We show that the mitigation of finite-size effects that typically skew the predicted melting temperatures in DFT–TPC simulations in excess of several hundred kelvin requires models with ∼16 000 atoms and >100 ps molecular dynamics trajectories. In addition, the DNP can successfully describe MgO metallization well at increased pressures that are captured by DFT but missed by classical interatomic potentials

Seedless Initiation as an Efficient, Sustainable Route to Anisotropic Gold Nanoparticles

Seedless initiation has been used as a simple and sustainable alternative to seed-mediated production of two canonical anisotropic gold nanoparticles: nanorods and nanoprisms. The concentration of reducing agent during the nucleation event was found to influence the resulting product morphology, producing nanorods with lengths from 30 to 630 nm and triangular or hexagonal prisms with vertex-to-vertex lengths ranging from 120 to over 700 nm. The seedless approach is then used to eliminate several chemical reagents and reactions steps from classic particle preparations while achieving almost identical nanoparticle products and product yields. Our results shed light on factors that influence (or do not influence) the evolution of gold nanoparticle shape and present a dramatically more efficient route to obtaining these architectures. Specifically, using these methods reduces the total amount of reagent needed to produce nanorods and nanoprisms by as much as 90 wt % and, to the best of our knowledge, has yielded the first report of spectroscopically discernible, colloidal gold nanoplates synthesized using a seedless methodology

Exploring the formation of gold/silver nanoalloys with gas-phase synthesis and machine-learning assisted simulations

International audienceWhile nanoalloys are of paramount scientific and practical interests, the main processes leading to their formation are still poorly understood. Key structural features in the alloy systems, including crystal phase, chemical ordering, and morphology, are challenging to control at the nanoscale, making it difficult to transfer their usage to industrial applications. In this contribution, we focus on the gold/silver system that has two of the most prevalent noble metals, and combine experiments with simulations to uncover the formation mechanisms at the atomic-level. Nanoparticles are produced using state-of-the-art inert-gas aggregation source and analyzed using transmission electron microscopy and energy-dispersive x-ray spectroscopy. Machine-learning-assisted molecular dynamics simulations are employed to model the crystallization process from liquid droplets to nanocrystals. Our study finds a preponderance of nanoparticles with five-fold symmetric morphology, including icosahedron and decahedron which is consistent with previous results on mono-metallic nanoparticles. However, we observe that gold atoms, rather than silver atoms, segregate at the surface of the obtained nanoparticles for all the considered alloy compositions. These segregation tendencies are in contrast to previous studies and have consequences on the crystallization dynamics and the subsequent crystal ordering. We finally show that the underpinnings of this surprising segregation dynamics is due to charge transfer and electrostatic interactions rather than surface energy considerations

Analysis of Lanthanide Complex Dendrimer Conjugates for Bimodal NIR and MRI Imaging

Advances in clinical diagnostic instrumentation have enabled some imaging modalities to be run concurrently. For diagnostic purposes, multimodal imaging can allow for rapid location and accurate identification of a patient’s illness. The paramagnetic and near-infrared (NIR) properties of Dy­(III) and Yb­(III) are interesting candidates for the development of bimodal NIR and magnetic resonance imaging (MRI) contrast agents. To enhance their intrinsic bimodal properties, these lanthanides were chelated using the hexadentate-all-oxygen-donor-ligand TREN-bis­(1-Me)-3,2-HOPO-TAM-NX (NX, where X = 1, 2, or 3) and subsequently conjugated to the esteramide dendrimer (EA) to improve bioavailability, solubility, and relaxivity. Of these new complexes synthesized and evaluated, DyN1-EA had the largest ionic <i>T</i>₁ relaxivity, 7.60 mM^–1 s^–1, while YbN3-EA had the largest ionic <i>T</i>₂ relaxivity with a NIR quantum yield of 0.17% when evaluated in mouse serum. This is the first Yb­(III) bimodal NIR/<i>T</i>₂ MRI contrast agent of its kind evaluated