Search for: All records

The Caribbean Through-Flow (CTF) is a critical chokepoint for North and South Atlantic waters that form the North Atlantic western boundary current system and the upper ocean limb of the Atlantic Meridional Overturning Circulation. While the circulation and energetics of the CTF have been well studied, its water mass transformations remain poorly constrained. Using over 7700 Argo float profiles from 2014 to 2024, we document a prominent westward modification in water mass structure across the Caribbean Sea. From the eastern to western Caribbean, we observe systematic increases in ocean heat content, a deepening of isopycnals, and a freshening and deepening of the subsurface salinity maximum. These changes result in a net mid-depth (~50–500 m) density reduction of 0.40 ± 0.27 kg m-3. We hypothesize that regional variations in mesoscale eddy activity, complex bathymetry, and meridional wind stress curl gradients drive this transformation. The resulting water mass structure has critical implications for regional climate, weather, ecosystems, and sea level rise, as it modifies the density and stratification of source waters entering the Gulf of Mexico and North Atlantic western boundary current system. Our findings highlight the importance of internal Caribbean processes in shaping upper-ocean heat and salt transport in the Atlantic and underscore the need for sustained in situ observations in the region and targeted modeling analyses of the underlying modification processes. 

ABSTRACT Technologies for large‐scale manufacturing of viral vectors for gene therapies, such as tangential flow filtration and membrane chromatography, are under development. In these early stages of process development, techno‐economic analyses are useful for identifying membrane properties yielding the greatest impact on process performance. In this study, we adapted a techno‐economic framework used for monoclonal antibody capture for adeno‐associated viral vector purification. We added mechanistic models to simulate flux decline during harvesting and separating full and empty capsids during polishing. Graphical user interfaces were added to help users explore the design search space. We selected a base process and manipulated selected variables to see their impact on large‐scale manufacturing performance. These sensitivity analyses revealed that, under the selected process conditions, increasing module capacity reduces cost of goods more effectively than increasing operational flux in tangential flow membrane filtration modules for virus harvesting. Membrane chromatography columns with relatively low dynamic binding capacity (DBC) and short residence time (RT) offered similar or better economic performance than those with high DBC and long RT. Additionally, the difference in equilibrium solid‐phase concentration between full and empty capsids as a function of salt concentration significantly affects purity. 

Abstract Continuous manufacturing platforms and membrane chromatography are process technologies with the potential to reduce production costs and minimize process variability in monoclonal antibody production. This study presents a simulation and optimization framework to perform techno‐economic analyses of these strategies. Multi‐objective optimization was used to compare batch and continuous multicolumn operating modes and membrane and resin process alternatives, revealing performance differences in productivity and cost of goods attributed to variations in dynamic binding capacity, media geometry, and process residence time. From the set of optimal process configurations, we selected one membrane and one resin platform alternative yielding the highest net present values to undergo sensitivity analyses involving variations in batch cadence and product selling price. For the scenarios considered in this work, membrane continuous platforms showed benefits in the cost of goods and process mass intensity. Their shorter residence time compared to resins positions them as a viable alternative for single‐use capture chromatography. Moreover, this low residence time makes membrane platforms more flexible to changes in throughput, an essential feature for integrating capture into fully continuous processes. 

Time-resolved spectroscopy is an important tool for probing photochemically induced nonequilibrium dynamics and energy transfer. Herein, a method is developed for the ab initio simulation of vibronic spectra and dynamical processes. This framework utilizes the recently developed nuclear–electronic orbital time-dependent configuration interaction (NEO-TDCI) approach, which treats all electrons and specified nuclei quantum mechanically on the same footing. A strategy is presented for calculating time-resolved vibrational and electronic absorption spectra from any initial condition. Although this strategy is general for any TDCI implementation, utilizing the NEO framework allows for the explicit inclusion of quantized nuclei, as illustrated through the calculation of vibrationally hot spectra. Time-resolved spectra produced by either vibrational or electronic Rabi oscillations capture ground-state absorption, stimulated emission, and excited-state absorption between vibronic states. This methodology provides the foundation for fully ab initio simulations of multidimensional spectroscopic experiments. 

Abstract We report the discovery of CHIME J1634+44, a long-period radio transient (LPT) unique for two aspects: it is the first known LPT to emit fully circularly polarized radio bursts, and it is the first LPT with a significant spin-up. Given that high circular polarization (>90%) has been observed in FRB 20201124A and in some giant pulses of PSR B1937+21, we discuss the implications of the high circular polarization of CHIME J1634+44 and conclude its emission mechanism is likely to be “pulsar-like.” While CHIME J1634+44 has a pulse period of 841 s, its burst arrival patterns are indicative of a secondary 4206 s period, probably associated with binary activity. The timing properties suggest it has a significantly negative period derivative of $\dot{P}=-9.03\left(0.11\right)\times {10}^{-12}$s s⁻¹. Few systems have been known to spin up, most notably transitional millisecond pulsars and cataclysmic binaries, both of which seem unlikely progenitors for CHIME J1634+44. If the period was only associated with the spin of the object, then the spin-up is likely generated by accretion of material from a companion. If, however, the radio pulse period and the orbital period are locked, as appears to be the case for two other LPTs, the spin-up of CHIME J1634+44 could be driven by gravitational-wave radiation. 

Adeno-associated viral vectors (AAVs) are the predominant viral vectors used for gene therapy applications. A significant challenge in obtaining effective doses is removing non-therapeutic empty viral capsids lacking DNA cargo. Current methods for separating full (gene-containing) and empty capsids are challenging to scale, produce low product yields, are slow, and are difficult to operationalize for continuous biomanufacturing. This communication demonstrates the feasibility of separating full and empty capsids by ultrafiltration. Separation performance was quantified by measuring the sieving coefficients for full and empty capsids using ELISA, qPCR, and an infectivity assay based on the live cell imaging of green fluorescent protein expression. We demonstrated that polycarbonate track-etched membranes with a pore size of 30 nm selectively permeated empty capsids to full capsids, with a high recovery yield (89%) for full capsids. The average sieving coefficients of full and empty capsids obtained through ELISA/qPCR were calculated as 0.25 and 0.49, indicating that empty capsids were about twice as permeable as full capsids. Establishing ultrafiltration as a viable unit operation for separating full and empty AAV capsids has implications for developing the scale-free continuous purification of AAVs.