Palladium (Pd)-based catalysts hold promise as an alternative water treatment technology for nitrate (NO3–), but practical application requires a flow-through reactor that efficiently delivers hydrogen (H2) from gas to water. A trickle bed reactor (TBR) packed with a 0.1 percent by weight (wt%) Pd–0.01 wt% In/γ-Al2O3 (indium and porous aluminum oxide) catalyst was evaluated to address this challenge. Catalytic activity generally increased with H2 superficial velocity (0.65–29.6 m/h) and liquid (deionized water) superficial velocities from 14.8 to 26.6 m/h before decreasing at 38.5 m/h. This decrease corresponded to a change in flow regime and suggests that optimal TBR performance occurs at the transition from pulse to bubble flow. An optimal TBR activity of 19.5 ± 1.3 mg NO3–/min-g Pd was obtained; this is only ~18% of the batch reactor activity as a result of H2 mass transfer limitations, but three to 15 times greater than activities obtained with previous flow-through reactors. Catalyst deactivation occurred in the TBR after 41 days of operation, motivating the need for improved fouling mitigation strategies.
Immune checkpoint therapy has become the first widely adopted immunotherapy for patients with late stage malignant melanoma, with potential for a wide range of cancers. While some patients can experience long term disease remission, this is limited only to a subset of patients and tumor types. The path forward to expand this therapy to more patients and tumor types is currently thought to be combinatorial treatments, the combination of immunotherapy with other treatments. In this review, the combinatorial approach of immune checkpoint therapy combined with nanoparticle-assisted localized hyperthermia is discussed, starting with an overview of the different nanoparticle hyperthermia approaches in development, an overview of the state of immune checkpoint therapy, recent reports of immune checkpoint therapy and nanoparticle-assisted hyperthermia in a combinatorial approach, and finally a discussion of future research topics and areas to be explored in this new combinatorial approach to cancer treatment.
Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4'-[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenyle ne] bis(oxy)dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of <100 nm diameter as determined by dynamic light scattering and electron microscopy. Both types of nanoparticles show strong absorption of light in the near infrared region, with absorption peaks at 780 nm for P1 and 750 nm for PEDOT, as well as high photothermal conversion efficiencies ( 50%), that is higher than commercially available gold-based photothermal ablation agents. The nanoparticles show significant photostability as determined by their ability to achieve consistent temperatures and to maintain their morphology upon repeated cycles of laser irradiation. In vitro studies in MDA-MB-231 breast cancer cells demonstrate the cytocompatibility of the CPNPs and their ability to mediate complete cancer cell ablation upon irradiation with an 808-nm laser, thereby establishing the potential of these systems as agents for laser-induced photothermal therapy.
To explain the effects of cationic amino acids and other co-solutes on the viscosity, stability and protein-protein interactions (PPI) of highly concentrated (≥200 mg/ml) monoclonal antibody (mAb) solutions to advance subcutaneous injection.
The viscosities of ≥200 mg/ml mAb1 solutions with various co-solutes and pH were measured by capillary rheometry in some cases up to 70,000 s−1. The viscosities are analyzed in terms of dilute PPI characterized by diffusion interaction parameters (kD) from dynamic light scattering (DLS). MAb stability was measured by turbidity and size exclusion chromatography (SEC) after 4 weeks of 40°C storage.
Viscosity reductions were achieved by reducing the pH, or adding histidine, arginine, imidazole or camphorsulfonic acid, each of which contains a hydrophobic moiety. The addition of inorganic electrolytes or neutral osmolytes only weakly affected viscosity. Systems with reduced viscosities also tended to be Newtonian, while more viscous systems were shear thinning.
Viscosity reduction down to 20 cP at 220 mg/ml mAb1 was achieved with co-solutes that are both charged and contain a hydrophobic interaction domain for sufficient binding to the protein surface. These reductions are related to the DLS diffusion interaction parameter, kD, only after normalization to remove the effect of charge screening. Shear rate profiles demonstrate that select co-solutes reduce protein network formation.
We present a time-depth relationship for Integrated Ocean Drilling Program (IODP) Expedition 341 Southern Alaska Margin Sites U1420 and U1421 using high-resolution multichannel seismic, core, and logging data. Calibrating and combining core and logging data at each site minimizes data gaps in physical properties information. Remaining data gaps were interpolated using spline fitting in order to provide continuous estimates of bulk density and compressional wave velocity for the full drilled interval. We use the interpolated physical property curves for bulk density and compressional wave velocity at each site to generate synthetic seismic traces. At Site U1421, vertical seismic profiling further constrained the time-depth relationship and was used to calibrate the velocity curve and provide input for the initial velocity model during the tie. Finally, we matched simulated reflectors in the synthetic trace with events in the nearby seismic traces and established a time-depth relationship at each site.
Nanoimprint lithography manufacturing utilizes a patterning technology that involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. The technology faithfully reproduces patterns with a higher resolution and greater uniformity compared to those produced by photolithography equipment. Throughputs of 80 wph have been demonstrated, and mix and match overlay of 3.7nm 3 sigma has been achieved. The technology has already been successfully applied as a demonstration to the fabrication of advanced NAND Flash memory devices. A similar approach can also be applied however to remove topography on an existing wafer, thereby creating a planar surface on which to pattern. In this paper, a novel adaptive planarization process is presented that addresses the problems associated with planarization of varying pattern densities, even in the presence of pre-existing substrate topography. The process is called Inkjet-enabled Adaptive Planarization (IAP). The IAP process uses an inverse optimization scheme, built around a validated fluid mechanics-based forward model that takes the pre-existing substrate topography and pattern layout as inputs. It then generates an inkjet drop pattern with a material distribution that is correlated with the desired planarization film profile. This allows a contiguous film to be formed with the desired thickness variation to cater to the topography and any parasitic signatures caused by the pattern layout. In this work, it was demonstrated that planarization efficiencies of up to 99.5% could be achieved, thereby reducing an initial similar to 100nm wafer topography down to as little as 0.6nm.