3D printed reactors and Kessil lamp holders for flow photochemistry: design and system standardization

A low-cost 3D printed standardized flow-photochemistry setup has been designed and developed for use with a pressure-driven flow system using photochemistry lamps available in most laboratories. In this research, photochemical reactors were 3D printed from polypropylene which facilitated rapid optimization of both reactor geometry and experimental setup of the lamp housing system. To exemplify the rapidity of this approach to optimization, a Kessil LED lamp was used in the bromination of a range of toluenes in the 3D printed reactors in good yields with residence times as low as 27 s. The reaction compared favorably with the batch photochemical procedure and was able to be scaled up to a productivity of 75 mmol h−1

Digitisation of a modular plug and play 3D printed continuous flow system for chemical synthesis

We describe the development of a digital modular 3D printed continuous flow system to carry out both classical and photochemical synthesis that uses a novel PC based software interface for communication. Using this system, we describe how we were able to both control and monitor reaction conditions at the same time. The system integrates in-line sensors via a simple cassette based system that is analogous to a retro-games console enabling hot-swapping of modules by a user. A PC-interface platform was created to automate both its functional control, including the injection of solvents, and the visualization of sensor-reported data. The utility of the system was demonstrated by performing a series of reactions highlighting the importance that precise control of solvent flow rate and accurate reporting of reaction temperatures can have on standardization and reproducibility and that the system can be easily modified to allow for scale-up synthesis

Classifying High-cadence Microlensing Light Curves I; Defining Features

Microlensing is a powerful tool for discovering cold exoplanets, and the The Roman Space Telescope microlensing survey will discover over 1000 such planets. Rapid, automated classification of Roman's microlensing events can be used to prioritize follow-up observations of the most interesting events. Machine learning is now often used for classification problems in astronomy, but the success of such algorithms can rely on the definition of appropriate features that capture essential elements of the observations that can map to parameters of interest. In this paper, we introduce tools that we have developed to capture features in simulated Roman light curves of different types of microlensing events, and evaluate their effectiveness in classifying microlensing light curves. These features are quantified as parameters that can be used to decide the likelihood that a given light curve is due to a specific type of microlensing event. This method leaves us with a list of parameters that describe features like the smoothness of the peak, symmetry, the number of peaks, and width and height of small deviations from the main peak. This will allow us to quickly analyze a set of microlensing light curves and later use the resulting parameters as input to machine learning algorithms to classify the events.Comment: 29 Pages, 30 Figures, 3 Tables, Accepted to the Astronomical Journa

3D Printed Tetrakis(triphenylphosphine)palladium (0) Impregnated Stirrer Devices for Suzuki-Miyaura Cross-Coupling Reactions

3D printed materials can be readily modified to create bespoke structures that incorporate a range of catalysts at the point of printing. In this present study we report on the design and 3D printing of tetrakis (triphenylphosphine) palladium (0) im-pregnated 3D printed stirrer devices that were used to catalyze a Suzuki-Miyaura reaction between biaryl compounds in a batch-based approach. It was shown that the devices themselves are reusable, easy to use, air-stable, give access to an array of biaryl compounds in excellent yields and lead to low levels of palladium loss into the reaction. Simple modification of the device’s design by size reduction, meant that they could also be used to reduce the time of the Suzuki-Miyaura reaction by microwave enhanced heating. At the end of the reaction, devices can simply be removed from the flask, washed and reused, analogous to stirrer bead workflows. This makes the overall process of setting up multiple reactions simpler by obviating the need to weigh out catalysts for reactions and the device, once used, can be simply removed from the reaction media at the end of the reaction

Supporting‐electrolyte‐free electrochemical methoxymethylation of alcohols using a 3D‐printed electrosynthesis continuous flow cell system

We describe the development of a novel low‐cost small‐footprint 3D‐printed electrosynthesis continuous flow cell system that was designed and adapted to fit a commercially available Electrasyn 2.0. The utility and effectiveness of the combined flow/electrochemistry system over the batch process was demonstrated in the development of an improved and supporting‐electrolyte‐free version of our anodic methoxymethylation of alcohols

3D-printed Franz cells - update on optimization of manufacture and evaluation

OBJECTIVES: Laboratory in vitro permeation processes require the use of modified Franz type diffusion cells which are conventionally fabricated from glass. Fragility and high cost are frequently associated with this type of laboratory apparatus. The purpose of our present research was to develop a simple, economical and versatile approach to manufacture Franz type cells using additive manufacturing (AM). METHODS: Graphical Franz diffusion cell designs were reproduced with a stereolithography (SLA) 3D printer and assessed over a minimum period of 24 h. The surface morphology of AM printouts was analysed before and after compatibility studies using scanning electron microscopy (SEM). Comparative permeation studies in both glass and AM Franz type diffusion cells were conducted using a caffeine solution (1.5 mg mL‑1), applied to a model silicone membrane. RESULTS: Testing of the 3D printed scaffolds confirmed similar recovery of the permeant when compared to glass cells: 1.49 ± 0.01 and 1.50 ± 0.01 mg mL‑1, respectively, after 72 h. No significant differences were visible from the SEM micrographs demonstrating consistent, smooth and non-porous surfaces of the AM Franz cells’ core structure. Permeation studies using transparent 3D printed constructs resulted in 12.85 ± 0.53 μg cm ‑2 caffeine recovery in the receptor solution after 180 min with comparable permeant recovery, 11.49 ± 1.04 μg cm ‑2, for the glass homologues. CONCLUSION: AM constructs can be considered as viable alternatives to the use of conventional glass apparatus offering a simple, reproducible and cost-effective method of replicating specialised laboratory glassware. A wider range of permeants will be investigated in future studies with these novel 3D printed Franz diffusion cells

The ATG5-binding and coiled coil domains of ATG16L1 maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3 associated phagocytosis

Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion with lysosomes. An autophagy-related pathway called LC3-associated phagocytosis (LAP) targets LC3 to phagosome and endosome membranes during uptake of bacterial and fungal pathogens, and targets LC3 to swollen endosomes containing particulate material or apoptotic cells. We have investigated the roles played by autophagy and LAP in vivo by exploiting the observation that the WD domain of ATG16L1 is required for LAP, but not autophagy. Mice lacking the linker and WD domains, activate autophagy, but are deficient in LAP. The LAP −/- mice survive postnatal starvation, grow at the same rate as littermate controls, and are fertile. The liver, kidney, brain and muscle of these mice maintain levels of autophagy cargoes such as LC3 and SQSTM1/p62 similar to littermate controls, and prevent accumulation of SQSTM1 inclusions and tissue damage associated with loss of autophagy. The results suggest that autophagy maintains tissue homeostasis in mice independently of LC3-associated phagocytosis. Further deletion of glutamate E230 in the coiled-coil domain required for WIPI2 binding produced mice with defective autophagy that survived neonatal starvation. Analysis of brain lysates suggested that interactions between WIPI2 and ATG16L1 were less critical for autophagy in the brain, which may allow a low level of autophagy to overcome neonatal lethality. Abbreviations: CCD: coiled-coil domain; CYBB/NOX2: cytochrome b-245: beta polypeptide; GPT/ALT: glutamic pyruvic transaminase: soluble; LAP: LC3-associated phagocytosis; LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; NOD: nucleotide-binding oligomerization domain; NADPH: nicotinamide adenine dinucleotide phosphate; RUBCN/Rubicon: RUN domain and cysteine-rich domain containing Beclin 1-interacting protein; SLE: systemic lupus erythematosus; SQSTM1/p62: sequestosome 1; TLR: toll-like receptor; TMEM: transmembrane protein; TRIM: tripartite motif-containing protein; UVRAG: UV radiation resistance associated gene; WD: tryptophan-aspartic acid; WIPI: WD 40 repeat domain: phosphoinositide interacting

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Three-Dimensional Printing of a Scalable Molecular Model and Orbital Kit for Organic Chemistry Teaching and Learning

Three-dimensional (3D) chemical models are a well-established learning tool used to enhance the understanding of chemical structures by converting two-dimensional paper or screen outputs into realistic three-dimensional objects. While commercial atom model kits are readily available, there is a surprising lack of large molecular and orbital models that could be used in large spaces. As part of a program investigating the utility of 3D printing in teaching, a modular size-adjustable molecular model and orbital kit was developed and produced using 3D printing and was used to enhance the teaching of stereochemistry, isomerism, hybridization, and orbitals