Flash NanoPrecipitation as an Agrochemical Nanocarrier Formulation Platform: Phloem Uptake and Translocation after Foliar Administration.

The increasing severity of pathogenic and environmental stressors that negatively affect plant health has led to interest in developing next-generation agrochemical delivery systems capable of precisely transporting active agents to specific sites within plants. In this work, we adapt Flash NanoPrecipitation (FNP), a scalable nanocarrier (NC) formulation technology used in the pharmaceutical industry, to prepare organic core-shell NCs and study their efficacy as foliar or root delivery vehicles. NCs ranging in diameter from 55 to 200 nm, with surface zeta potentials from -40 to +40 mV, and with seven different shell material properties were prepared and studied. Shell materials included synthetic polymers poly(acrylic acid), poly(ethylene glycol), and poly(2-(dimethylamino)ethyl methacrylate), naturally occurring compounds fish gelatin and soybean lecithin, and semisynthetic hydroxypropyl methylcellulose acetate succinate (HPMCAS). NC cores contained a gadolinium tracer for tracking by mass spectrometry, a fluorescent dye for tracking by confocal microscopy, and model hydrophobic compounds (alpha tocopherol acetate and polystyrene) that could be replaced by agrochemical payloads in subsequent applications. After foliar application onto tomato plants with Silwet L-77 surfactant, internalization efficiencies of up to 85% and NC translocation efficiencies of up to 32% were observed. Significant NC trafficking to the stem and roots suggests a high degree of phloem loading for some of these formulations. Results were corroborated by confocal microscopy and synchrotron X-ray fluorescence mapping. NCs stabilized by cellulosic HPMCAS exhibited the highest degree of translocation, followed by formulations with a significant surface charge. The results from this work indicate that biocompatible materials like HPMCAS are promising agrochemical delivery vehicles in an industrially viable pharmaceutical nanoformulation process (FNP) and shed light on the optimal properties of organic NCs for efficient foliar uptake, translocation, and delivery.

The Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D) at the Spallation Neutron Source (invited).

The Oak Ridge National Laboratory is planning to build the Second Target Station (STS) at the Spallation Neutron Source (SNS). STS will host a suite of novel instruments that complement the First Target Station's beamline capabilities by offering an increased flux for cold neutrons and a broader wavelength bandwidth. A novel neutron imaging beamline, named the Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D), is among the first eight instruments that will be commissioned at STS as part of the construction project. CUPI2D is designed for a broad range of neutron imaging scientific applications, such as energy storage and conversion (batteries and fuel cells), materials science and engineering (additive manufacturing, superalloys, and archaeometry), nuclear materials (novel cladding materials, nuclear fuel, and moderators), cementitious materials, biology/medical/dental applications (regenerative medicine and cancer), and life sciences (plant-soil interactions and nutrient dynamics). The innovation of this instrument lies in the utilization of a high flux of wavelength-separated cold neutrons to perform real time in situ neutron grating interferometry and Bragg edge imaging-with a wavelength resolution of δλ/λ ≈ 0.3%-simultaneously when required, across a broad range of length and time scales. This manuscript briefly describes the science enabled at CUPI2D based on its unique capabilities. The preliminary beamline performance, a design concept, and future development requirements are also presented.

Loss of OPT3 function decreases phloem copper levels and impairs crosstalk between copper and iron homeostasis and shoot-to-root signaling in Arabidopsis thaliana.

Copper (Cu) and iron (Fe) are essential micronutrients that are toxic when accumulating in excess in cells. Thus, their uptake by roots is tightly regulated. While plants sense and respond to local Cu availability, the systemic regulation of Cu uptake has not been documented in contrast to local and systemic control of Fe uptake. Fe abundance in the phloem has been suggested to act systemically, regulating the expression of Fe uptake genes in roots. Consistently, shoot-to-root Fe signaling is disrupted in Arabidopsis thaliana mutants lacking the phloem companion cell-localized Fe transporter, OLIGOPEPTIDE TRANSPORTER 3 (AtOPT3). We report that AtOPT3 also transports Cu in heterologous systems and contributes to its delivery from sources to sinks in planta. The opt3 mutant contained less Cu in the phloem, was sensitive to Cu deficiency and mounted a transcriptional Cu deficiency response in roots and young leaves. Feeding the opt3 mutant and Cu- or Fe-deficient wild-type seedlings with Cu or Fe via the phloem in leaves downregulated the expression of both Cu- and Fe-deficiency marker genes in roots. These data suggest the existence of shoot-to-root Cu signaling, highlight the complexity of Cu/Fe interactions, and the role of AtOPT3 in fine-tuning root transcriptional responses to the plant Cu and Fe needs.

Compositionally complex doping for zero-strain zero-cobalt layered cathodes.

The high volatility of the price of cobalt and the geopolitical limitations of cobalt mining have made the elimination of Co a pressing need for the automotive industry1. Owing to their high energy density and low-cost advantages, high-Ni and low-Co or Co-free (zero-Co) layered cathodes have become the most promising cathodes for next-generation lithium-ion batteries2,3. However, current high-Ni cathode materials, without exception, suffer severely from their intrinsic thermal and chemo-mechanical instabilities and insufficient cycle life. Here, by using a new compositionally complex (high-entropy) doping strategy, we successfully fabricate a high-Ni, zero-Co layered cathode that has extremely high thermal and cycling stability. Combining X-ray diffraction, transmission electron microscopy and nanotomography, we find that the cathode exhibits nearly zero volumetric change over a wide electrochemical window, resulting in greatly reduced lattice defects and local strain-induced cracks. In-situ heating experiments reveal that the thermal stability of the new cathode is significantly improved, reaching the level of the ultra-stable NMC-532. Owing to the considerably increased thermal stability and the zero volumetric change, it exhibits greatly improved capacity retention. This work, by resolving the long-standing safety and stability concerns for high-Ni, zero-Co cathode materials, offers a commercially viable cathode for safe, long-life lithium-ion batteries and a universal strategy for suppressing strain and phase transformation in intercalation electrodes.

Iraq/Afghanistan war lung injury reflects burn pits exposure.

This descriptive case series retrospectively reviewed medical records from thirty-one previously healthy, war-fighting veterans who self-reported exposure to airborne hazards while serving in Iraq and Afghanistan between 2003 and the present. They all noted new-onset dyspnea, which began during deployment or as a military contractor. Twenty-one subjects underwent non-invasive pulmonary diagnostic testing, including maximum expiratory pressure (MEP) and impulse oscillometry (IOS). In addition, five soldiers received a lung biopsy; tissue results were compared to a previously published sample from a soldier in our Iraq Afghanistan War Lung Injury database and others in our database with similar exposures, including burn pits. We also reviewed civilian control samples (5) from the Stony Brook University database. Military personnel were referred to our International Center of Excellence in Deployment Health and Medical Geosciences, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell under the auspices of Northwell IRB: 17-0140-FIMR Feinstein Institution for Medical Research "Clinicopathologic characteristics of Iraq Afghanistan War Lung Injury." We retrospectively examined medical records, including exposure data, radiologic imaging, and non-invasive pulmonary function testing (MGC Diagnostic Platinum Elite Plethysmograph) using the American Thoracic Society (ATS) standard interpretation based on Morgan et al., and for a limited cohort, biopsy data. Lung tissue, when available, was examined for carbonaceous particles, polycyclic aromatic hydrocarbons (Raman spectroscopy), metals, titanium connected to iron (Brookhaven National Laboratory, National Synchrotron Light Source II, Beamline 5-ID), oxidized metals, combustion temperature, inflammatory cell accumulation and fibrosis, neutrophil extracellular traps, Sirius red, Prussian Blue, as well as polarizable crystals/particulate matter/dust. Among twenty-one previously healthy, deployable soldiers with non-invasive pulmonary diagnostic tests, post-deployment, all had severely decreased MEP values, averaging 42% predicted. These same patients concurrently demonstrated abnormal airways reactance (X5Hz) and peripheral/distal airways resistance (D5-D20%) via IOS, averaging - 1369% and 23% predicted, respectively. These tests support the concept of airways hyperresponsiveness and distal airways narrowing, respectively. Among the five soldiers biopsied, all had constrictive bronchiolitis. We detected the presence of polycyclic aromatic hydrocarbons (PAH)-which are products of incomplete combustion-in the lung tissue of all five warfighters. All also had detectable titanium and iron in the lungs. Metals were all oxidized, supporting the concept of inhaling burned metals. Combustion temperature was consistent with that of burned petrol rather than higher temperatures noted with cigarettes. All were nonsmokers. Neutrophil extracellular traps were reported in two biopsies. Compared to our prior biopsies in our Middle East deployment database, these histopathologic results are similar, since all database biopsies have constrictive bronchiolitis, one has lung fibrosis with titanium bound to iron in fixed mathematical ratios of 1:7 and demonstrated polarizable crystals. These results, particularly constrictive bronchiolitis and polarizable crystals, support the prior data of King et al. (N. Engl. J. Med. 365:222-230, 2011) Soldiers in this cohort deployed to Iraq and Afghanistan since 2003, with exposure to airborne hazards, including sandstorms, burn pits, and improvised explosive devices, are at high risk for developing chronic clinical respiratory problems, including: (1) reduction in respiratory muscle strength; (2) airways hyperresponsiveness; and (3) distal airway narrowing, which may be associated with histopathologic evidence of lung damage, reflecting inhalation of burned particles from burn pits along with particulate matter/dust. Non-invasive pulmonary diagnostic tests are a predictor of burn pit-induced lung injury.

Subsurface Cooling Rates and Microstructural Response during Laser Based Metal Additive Manufacturing.

Laser powder bed fusion (LPBF) is a method of additive manufacturing characterized by the rapid scanning of a high powered laser over a thin bed of metallic powder to create a single layer, which may then be built upon to form larger structures. Much of the melting, resolidification, and subsequent cooling take place at much higher rates and with much higher thermal gradients than in traditional metallurgical processes, with much of this occurring below the surface. We have used in situ high speed X-ray diffraction to extract subsurface cooling rates following resolidification from the melt and above the ß-transus in titanium alloy Ti-6Al-4V. We observe an inverse relationship with laser power and bulk cooling rates. The measured cooling rates are seen to correlate to the level of residual strain borne by the minority ß-Ti phase with increased strain at slower cooling rates. The α-Ti phase shows a lattice contraction which is invariant with cooling rate. We also observe a broadening of the diffraction peaks which is greater for the ß-Ti phase at slower cooling rates and a change in the relative phase fraction following LPBF. These results provide a direct measure of the subsurface thermal history and demonstrate its importance to the ultimate quality of additively manufactured materials.

Anode Overpotential Control via Interfacial Modification: Inhibition of Lithium Plating on Graphite Anodes.

Lithium-metal deposition on graphite anodes limits the cycle life and negatively impacts safety of the current state of the art Li-ion batteries. Herein, deliberate interfacial modification of graphite electrodes via direct current (DC) magnetron sputtering of nanoscale layers of Cu and Ni is employed to increase the overpotential for Li deposition and suppress Li plating under high rate charge conditions. Due to their nanoscale, the deposited surface films have minimal impact (∼0.16% decrease) on cell level theoretical energy density. Interfacial properties of the anodes are thoroughly characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and spatially resolved mapping X-ray absorption near edge structure (XANES) spectroscopy. The spectroscopic measurements indicate that the Cu and Ni coatings form oxide upon exposure to an ambient environment, but they are reduced within the electrochemical cell and remain in a metallic state. Li plating is quantified by X-ray diffraction and associated electrochemistry measurements revealing that the surface treatment effectively reduces the quantity of the plated Li metal by ∼50% compared to untreated electrodes. These results establish an effective method using interfacial modification to achieve deliberate control of Li-metal deposition overpotential and reduction of lithium plating on graphite.

Dynamics of pore formation during laser powder bed fusion additive manufacturing.

Laser powder bed fusion additive manufacturing is an emerging 3D printing technique for the fabrication of advanced metal components. Widespread adoption of it and similar additive technologies is hampered by poor understanding of laser-metal interactions under such extreme thermal regimes. Here, we elucidate the mechanism of pore formation and liquid-solid interface dynamics during typical laser powder bed fusion conditions using in situ X-ray imaging and multi-physics simulations. Pores are revealed to form during changes in laser scan velocity due to the rapid formation then collapse of deep keyhole depressions in the surface which traps inert shielding gas in the solidifying metal. We develop a universal mitigation strategy which eliminates this pore formation process and improves the geometric quality of melt tracks. Our results provide insight into the physics of laser-metal interaction and demonstrate the potential for science-based approaches to improve confidence in components produced by laser powder bed fusion.

Deliberate Modification of Fe3O4 Anode Surface Chemistry: Impact on Electrochemistry.

Fe3O4 nanoparticles (NPs) with an average size of 8-10 nm have been successfully functionalized with various surface-treatment agents to serve as model systems for probing surface chemistry-dependent electrochemistry of the resulting electrodes. The surface-treatment agents used for the functionalization of Fe3O4 anode materials were systematically varied to include aromatic or aliphatic structures: 4-mercaptobenzoic acid, benzoic acid (BA), 3-mercaptopropionic acid, and propionic acid (PA). Both structural and electrochemical characterizations have been used to systematically correlate the electrode functionality with the corresponding surface chemistry. Surface treatment with ligands led to better Fe3O4 dispersion, especially with the aromatic ligands. Electrochemistry was impacted where the PA- and BA-treated Fe3O4 systems without the -SH group demonstrated a higher rate capability than their thiol-containing counterparts and the pristine Fe3O4. Specifically, the PA system delivered the highest capacity and cycling stability among all samples tested. Notably, the aromatic BA system outperformed the aliphatic PA counterpart during extended cycling under high current density, due to the improved charge transfer and ion transport kinetics as well as better dispersion of Fe3O4 NPs, induced by the conjugated system. Our surface engineering of the Fe3O4 electrode presented herein, highlights the importance of modifying the structure and chemistry of surface-treatment agents as a plausible means of enhancing the interfacial charge transfer within metal oxide composite electrodes without hampering the resulting tap density of the resulting electrode.

An instrument for in situ time-resolved X-ray imaging and diffraction of laser powder bed fusion additive manufacturing processes.

In situ X-ray-based measurements of the laser powder bed fusion (LPBF) additive manufacturing process produce unique data for model validation and improved process understanding. Synchrotron X-ray imaging and diffraction provide high resolution, bulk sensitive information with sufficient sampling rates to probe melt pool dynamics as well as phase and microstructure evolution. Here, we describe a laboratory-scale LPBF test bed designed to accommodate diffraction and imaging experiments at a synchrotron X-ray source during LPBF operation. We also present experimental results using Ti-6Al-4V, a widely used aerospace alloy, as a model system. Both imaging and diffraction experiments were carried out at the Stanford Synchrotron Radiation Lightsource. Melt pool dynamics were imaged at frame rates up to 4 kHz with a ∼1.1 µm effective pixel size and revealed the formation of keyhole pores along the melt track due to vapor recoil forces. Diffraction experiments at sampling rates of 1 kHz captured phase evolution and lattice contraction during the rapid cooling present in LPBF within a ∼50 × 100 µm area. We also discuss the utility of these measurements for model validation and process improvement.

Continuous-scan capability at SSRL and applications to X-ray diffraction.

Typical X-ray diffraction measurements are made by moving a detector to discrete positions in space and then measuring the signal at each stationary position. This step-scanning method can be time-consuming, and may induce vibrations in the measurement system when the motors are accelerated and decelerated at each position. Furthermore, diffraction information between the data points may be missed unless a fine step-scanning is used, which further increases the total measurement time. To utilize beam time efficiently, the motor acceleration and deceleration time should be minimized, and the signal-to-noise ratio should be maximized. To accomplish this, an integrated continuous-scan system was developed at the Stanford Synchrotron Radiation Lightsource (SSRL). The continuous-scan system uses an in-house integrated motor controller system and counter/timer electronics. SPEC software is used to control both the hardware and data acquisition systems. The time efficiency and repeatability of the continuous-scan system were tested using X-ray diffraction from a ZnO powder and compared with the step-scan technique. Advantages and limitations of the continuous-scan system and a demonstration of variable-velocity continuous scan are discussed.

In situ heater design for nanoscale synchrotron-based full-field transmission X-ray microscopy.

The oxidation of nickel powder under a controlled gas and temperature environment was studied using synchrotron-based full-field transmission X-ray microscopy. The use of this technique allowed for the reaction to be imaged in situ at 55 nm resolution. The setup was designed to fit in the limited working distance of the microscope and to provide the gas and temperature environments analogous to solid oxide fuel cell operating conditions. Chemical conversion from nickel to nickel oxide was confirmed using X-ray absorption near-edge structure. Using an unreacted core model, the reaction rate as a function of temperature and activation energy were calculated. This method can be applied to study many other chemical reactions requiring similar environmental conditions.

Evaluation of serum biomarkers IL-17 and CTX for BRONJ: a pilot clinical case-control study.

A serious complication of bisphosphonate (BP) therapy is BP-related osteonecrosis of the jaw (BRONJ). Currently, no biomarkers exist to identify patients at risk. We evaluated whether interleukin-17 and C-telopeptide correlate with BRONJ development. We conducted a case-control study using patients with a history of BP therapy. Quantitative enzyme-linked immunosorbent assay and Student's t-test were done. Both markers were significantly higher in BRONJ, suggesting altered immune responses and bone remodeling may play roles in BRONJ development.

Three-dimensional microstructural imaging methods for energy materials.

Advances in the design of materials for energy storage and conversion (i.e., "energy materials") increasingly rely on understanding the dependence of a material's performance and longevity on three-dimensional characteristics of its microstructure. Three-dimensional imaging techniques permit the direct measurement of microstructural properties that significantly influence material function and durability, such as interface area, tortuosity, triple phase boundary length and local curvature. Furthermore, digital representations of imaged microstructures offer realistic domains for modeling. This article reviews state-of-the-art methods, across a spectrum of length scales ranging from atomic to micron, for three-dimensional microstructural imaging of energy materials. The review concludes with an assessment of the continuing role of three-dimensional imaging in the development of novel materials for energy applications.

Population pharmacokinetic and pharmacodynamic modeling for assessing risk of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: We hypothesized that patients with bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) accumulate higher levels of BP in bone than those without BRONJ. STUDY DESIGN: Using the Pmetrics package and published data, we designed a population pharmacokinetic model of pamidronate concentration in plasma and bone and derived a toxic bone BP threshold of 0.2 mmol/L. With the model, and using patient individual BP duration and bone mineral content estimated from lean body weight, we calculated bone BP levels in 153 subjects. RESULTS: Mean bone BP in 69 BRONJ cases was higher than in 84 controls (0.20 vs 0.10 mmol/L, P < 0.001), consistent with the toxic bone threshold of 0.2 mmol/L. BRONJ was also associated with longer duration BP therapy (5.3 vs 2.7 years, P < 0.001), older age (76 vs 70 years, P < 0.001), and Asian race (49% vs 14%, P < 0.001). CONCLUSIONS: Our model accurately discriminated BRONJ cases from controls among patients on BP therapy.

Nondestructive volumetric 3-D chemical mapping of nickel-sulfur compounds at the nanoscale.

Nano-structures of nickel (Ni) and nickel subsulfide (Ni(3)S(2)) materials were studied and mapped in 3D with high-resolution x-ray nanotomography combined with full field XANES spectroscopy. This method for characterizing these phases in complex microstructures is an important new analytical imaging technique, applicable to a wide range of nanoscale and mesoscale electrochemical systems.

Dissecting amelogenin protein nanospheres: characterization of metastable oligomers.

Amelogenin self-assembles to form an extracellular protein matrix, which serves as a template for the continuously growing enamel apatite crystals. To gain further insight into the molecular mechanism of amelogenin nanosphere formation, we manipulated the interactions between amelogenin monomers by altering pH, temperature, and protein concentration to create isolated metastable amelogenin oligomers. Recombinant porcine amelogenins (rP172 and rP148) and three different mutants containing only a single tryptophan (Trp(161), Trp(45), and Trp(25)) were used. Dynamic light scattering and fluorescence studies demonstrated that oligomers were metastable and in constant equilibrium with monomers. Stable oligomers with an average hydrodynamic radius (R(H)) of 7.5 nm were observed at pH 5.5 between 4 and 10 mg · ml(-1). We did not find any evidence of a significant increase in folding upon self-association of the monomers into oligomers, indicating that they are disordered. Fluorescence experiments with single tryptophan amelogenins revealed that upon oligomerization the C terminus of amelogenin (around residue Trp(161)) is exposed at the surface of the oligomers, whereas the N-terminal region around Trp(25) and Trp(45) is involved in protein-protein interaction. The truncated rP148 formed similar but smaller oligomers, suggesting that the C terminus is not critical for amelogenin oligomerization. We propose a model for nanosphere formation via oligomers, and we predict that nanospheres will break up to form oligomers in mildly acidic environments via histidine protonation. We further suggest that oligomeric structures might be functional components during maturation of enamel apatite.