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Poly(styrenyl acetal trehalose) (pSAT), composed of trehalose side chains linked to a polystyrene backbone via acetals, stabilizes a variety of proteins and enzymes against fluctuations in temperature. A promising application of pSAT is conjugation of the polymer to therapeutic proteins to reduce renal clearance. To explore this possibility, the safety of the polymer was first studied. Investigation of acute toxicity of pSAT in mice showed that there were no adverse effects of the polymer at a high (10 mg/kg) concentration. The immune response (antipolymer antibody and cytokine production) in mice was also studied. No significant antipolymer IgG was detected for pSAT, and only a transient and low level of IgM was elicited. pSAT was also safe in terms of cytokine response. The polymer was then conjugated to a granulocyte colony stimulating factor (GCSF), a therapeutic protein that is approved by the Federal Drug Administration, in order to study the biodistribution of a pSAT conjugate. A site-selective, two-step synthesis approach was developed for efficient conjugate preparation for the biodistribution study resulting in 90% conjugation efficiency. The organ distribution of GCSF-pSAT was measured by positron emission tomography and compared to controls GCSF and GCSF-poly(ethylene glycol), which confirmed that the trehalose polymer conjugate improved the in vivo half-life of the protein by reducing renal clearance. These findings suggest that trehalose styrenyl polymers are promising for use in therapeutic protein-polymer conjugates for reduced renal clearance of the biomolecule.

Insulin, the oldest U.S. Food and Drug Administration (FDA)-approved recombinant protein and a World Health Organization (WHO) essential medicine for treating diabetes globally, faces challenges due to its storage instability. One approach to stabilize insulin is the addition of poly(trehalose methacrylate) (pTrMA) as an excipient. The polymer increases the stability of the peptide to heat and mechanical agitation and has a low viscosity suitable for injection and pumps. However, the safety and stabilizing mechanism of pTrMA is not yet known and is required to understand the potential suitability of pTrMA as an insulin excipient. Herein is reported the immune response, biodistribution, and insulin plasma lifetime in mice, as well as investigation into insulin stabilization. pTrMA alone or formulated with ovalbumin did not elicit an antibody response over 3 weeks in mice, and there was no observable cytokine production in response to pTrMA. Micropositron emission tomography/microcomputer tomography of

Electrochemical CO2 reduction over Cu could provide value-added multicarbon hydrocarbons and alcohols. Despite recent breakthroughs, it remains a significant challenge to design a catalytic system with high product selectivity. Here we demonstrate that a high selectivity of ethylene (55%) and C2+ products (77%) could be achieved by a highly modular tricomponent copolymer modified Cu electrode, rivaling the best performance using other modified polycrystalline Cu foil catalysts. Such a copolymer can be conveniently prepared by a ring-opening metathesis polymerization, thereby offering a new degree of freedom for tuning the selectivity. Control experiments indicate all three components are essential for the selectivity enhancement. A surface characterization showed that the incorporation of a phenylpyridinium component increased the film robustness against delamination. It was also shown that its superior performance is not due to a morphology change of the Cu underneath. Molecular dynamics (MD) simulations indicate that a combination of increased local CO2 concentration, increased porosity for gas diffusion, and the local electric field effect together contribute to the increased ethylene and C2+ product selectivity.

Summary Shallow defects are mostly benign in covalent semiconductors, such as silicon, given that they do not constitute non-radiative recombination sites. In contrast, the existence of shallow defects in ionic perovskite crystals might have significant repercussions on the long-term stability of perovskite solar cells (PSCs) because of the metastability of the ubiquitous formamidinium lead triiodide (FAPbI3) perovskite and the migration of charged point defects. Here, we show that shallow iodine interstitial defects ( I i ) can be generated unintentionally during commonly used post-fabrication treatments, which can lower the cubic-to-hexagonal transformation barrier of FAPbI3-based perovskites to accelerate its phase degradation. We demonstrate that concurrently avoiding the generation of I i and the more effective passivation of iodine vacancies ( V I ) can improve the thermodynamic stability of the films and operational stability of the PSCs. Our most stable PSC retained 92.1 % of its initial performance after nearly 1,000 h of continuous illumination operational stability testing.

In this article, finite element method (FEM) based tool stress analysis and breakage prediction are advanced for meso-scale shoulder milling of hardened stainless steel. Rather than using simplified line loads or uniformly distributed loads, the tool stress analyses are conducted with realistic chip load predicted by the previously developed 3D coupled Eulerian-Lagrangian (CEL) FEM model. A reliable distribution of contact forces obtained with a continuous tool-chip contact region is transferred to a static FEM model for tool stress analysis and breakage prediction at each angular location of an end mill. The simulation results are validated through dedicated cutting experiments with short cutting distances under various cutting conditions. The developed FEM models are found to be capable of making accurate predictions of tool breakage. Some key features of feed rate-related tool breakage are identified. It is found that the maximum tensile stress in the tool does not coincide with the maximum resultant cutting force in terms of cutter rotation. The tensile stress in the tool is not positively correlated with the resultant cutting force. In down milling, the maximum tensile stress is found to occur just after the tool starts to contact with the workpiece. It is also observed that the tensile stresses of the tool are much smaller in up milling configuration compared to down milling processes.

Polymers that stabilize biomolecules are important as excipients in protein formulation. Herein, we describe a class of degradable polymers that have tunable degradation rates depending on the polymer backbone and are able to stabilize proteins to aggregation. Specifically, zwitterion- and trehalose-substituted polycaprolactone, polyvalerolactone, polycarbonate, and polylactide were prepared and characterized with regards to their hydrolytic degradation and ability to stabilize insulin to mechanical agitation during heat. Ring-opening polymerization (ROP) of allyl-substituted monomers was carried out using organocatalysis, resulting in well-defined alkene-substituted polymers with good control over molecular weight and dispersity. The polymers were then modified using photocatalyzed thiol-ene reactions to install protein-stabilizing carboxybetaine and trehalose side chains. The resulting polymers were water-soluble and exhibited a wide range of half-lives, from 12 hours to more than 4 months. The polymers maintained the ability to stabilize the therapeutic protein insulin from activity loss due to aggregation, demonstrating their potential as degradable excipients for protein formulation.

Traceless self-immolative linkers are widely used for the reversible modification of proteins and peptides. This article describes a new class of traceless linkers based on

α-Oxygenated Z -olefins are ubiquitous in biologically active molecules and serve as versatile handles for organic synthesis, but their syntheses are often tedious and less selective. Here we report the efficient Z -selective metathesis of various terminal acrylates and allyl alcohols, which enables facile and selective construction of high value-added α-oxygenated Z -olefins from readily available feedstock chemicals. These challenging metathesis transformations are enabled by novel cyclometalated Ru-carbene-nitrate complexes bearing bulky-yet-flexible side arms, whose assembly was unlocked by new organometallic syntheses.

In liquid crystal (LC) displays, deriving an optimum resistance level of an LC alignment polyimide (PI) layer is important because of the trade-off between the voltage holding and surface-discharging properties. In particular, to apply a power-saving low-frequency operation scheme to fringe-field switching (FFS) LC modes with negative dielectric LC (n-LC), delicate material engineering is required to avoid surface-charge-dependent image flickering and sticking problems, which severely degrade with lowering operation frequency. Therefore, this paper proposes a photocontrolled variable-resistivity PI layer in order to systematically investigate the voltage holding and discharging properties of the FFS n-LC modes, according to the PI resistivity (ρ) levels. By doping fullerene into the high-ρ PI as the photoexcited charge-generating nanoparticles, the ρ levels of the PI were continuously controllable with a wide tunable range (0.95 × 1015 Ω∙cm to 5.36 × 1013 Ω∙cm) through Ar laser irradiation under the same LC and LC alignment conditions. The frequency-dependent voltage holding and discharge behaviors were analyzed with photocontrolled ρ variation. Thus, the proposed experimental scheme is a feasible approach in PI engineering for a power-saving low-frequency FFS n-LC mode without the image flickering and image sticking issues.

Electrochemical CO

The efficient Z-selective cross-metathesis between acrylamides and common terminal olefins has been developed by the use of novel cyclometalated ruthenium catalysts with bulky N-heterocyclic carbene (NHC) ligands. Superior reactivity and stereoselectivity are realized for the first time in this challenging transformation, allowing streamlined access to an important class of cis-Michael acceptors from readily available feedstocks. The kinetic preference for cross-metathesis is enabled by a pivalate anionic ligand, and the origin of this effect is elucidated by density functional theory calculations.

The efficient

The Lewis acid–base adduct approach has been widely used to form uniform perovskite films, which has provided a methodological base for the development of high-performance perovskite solar cells. However, its incompatibility with formamidinium (FA)-based perovskites has impeded further enhancement of photovoltaic performance and stability. Here, we report an efficient and reproducible method to fabricate highly uniform FAPbI3 films via the adduct approach. Replacement of the typical Lewis base dimethyl sulfoxide (DMSO) with N-methyl-2-pyrrolidone (NMP) enabled the formation of a stable intermediate adduct phase, which can be converted into a uniform and pinhole-free FAPbI3 film. Infrared and computational analyses revealed a stronger interaction between NMP with the FA cation than DMSO, which facilitates the formation of a stable FAI·PbI2·NMP adduct. On the basis of the molecular interactions with different Lewis bases, we proposed criteria for selecting the Lewis bases. Owed to the high film quality, per...

In this article, a 3-dimensional Eulerian finite element method (FEM) model is introduced for simulation of end milling processes based on Abaqus/Explicit. Through the Coupled Eulerian Lagrangian (CEL) approach in model formulation, the chip formation process does not rely on the degradation of material or continuous remeshing algorithms to achieve chip separation. The process under investigation is the slot milling of Al6061-T6. A linear motion of the workpiece is adopted as a simplification of the trochoidal motion of the end mill. The workpiece is given a sinusoidal profile to achieve a varying uncut chip thickness in the cutting process. With a stationary tool and a confined region of mesh refinement, the computational cost of the model can be minimized. The model demonstrates good accuracy in cutting force predictions. The prediction error of the resultant cutting forces can be controlled within 12%. The proposed model also gives accurate predictions in terms of the morphology of chips. The excessive curling of chips in the early stages of chip formation can be predicted in the simulation process. The information obtained from the FEM model will provide more insights into the interactions between the cutting tool and the workpiece.

In this article, the dynamic modelling of machining process for high aspect ratio workpiece is presented considering the tool-workpiece compliance. The geometric surface of high aspect ratio workpiece is digitized and the dynamic interaction between cutting tool and workpiece is calculated in time domain. The transfer function from both cutting tool and workpiece is integrated with directional coefficients derived from forces and dynamic uncut chip thickness equations. The integrated time domain model considers three directional vibrations with consideration of workpiece and tooling vibration modes. Since workpiece movement continuously changes the dynamic uncut chip thickness in conjunction with tool movement, the workpiece surface nodes need to be continually updated for the prediction of the regenerative chatter. Especially the small diameter of workpiece may cause the dynamic shift in conjunction with cutting conditions. Traditional frequency domain models with simplified directional coefficients have limitations in the prediction of machining stability for high aspect ratio workpiece due to the nonlinear factors in directional coefficients. Finally, the predictions from the time domain model are compared with the experimental results.

Proteins are an important class of therapeutics that have advantages including high target specificity, but challenges to their use include rapid clearance and low physical stability. Conjugation of synthetic polymers is an effective approach to address the drawbacks and enhance other properties such as solubility. In this review, we present various considerations in synthesizing protein-polymer conjugates for therapeutic applications with a focus on the choice of polymer, protein, and conjugation method, as well as characterization and evaluation of the resulting conjugate in order to maximize the therapeutic potential of the protein drug.

Fluorine-containing polymers have potential for use in medicine and other applications, but the synthesis of degradable fluorous polymers is underexplored. In this report, we present a facile route to degradable fluorinated polymers and characterize the effect of fluorous comonomer identity on the polymerization as well as the degradation kinetics of the resulting polymer. Copolymers of poly(ethylene glycol methyl ether methacrylate) (PEGMA), fluorous methacrylate (1H,1H,2H,2H-perfluorooctyl or 1H,1H,2H,2H,3H,3H-perfluoropentyl methacrylate), and cyclic ketene acetal 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) were synthesized via ruthenium-catalyzed living radical polymerization. It was observed that increasing the fluorous monomer content led to enhanced BMDO incorporation in the resulting polymer. Density functional theory calculations suggest that this is due to the decreased energy gap between the singly occupied molecular orbital (SOMO) of the methacrylate radical and the highest occupied molecular o...

An easy-to-implement science outreach demonstration featuring a mechanically and photochemically color-changing polymer is described. The active polymeric material is a filled poly(dimethylsiloxane) (PDMS) elastomer that is covalently functionalized with spiropyran (SP), which is both a photochemical and mechanochemical switch. The material can be reversibly changed from colorless to dark purple by exposing it to light from a blue laser pointer or providing a mechanical stimulus such as hitting the polymer with a hammer or dragging a blunt object across the surface. The keynote demonstration is a PDMS chemical-drawing board that allows children literally to “write without ink” using a laser pointer or a blunt stylus. Collectively, these demonstrations are suitable for various student groups and encompass concepts in polymer and materials chemistry, photochemistry, and mechanochemistry. This demonstration has been successfully employed dozens of times in multiple universities across North America.

There is considerable interest in the use of proteins as therapeutics and as chemical and biochemical reagents. However, many proteins are unstable and aggregate when exposed to stressors, including increased temperature, pH change, agitation, and desiccation. Polymers with side chain trehalose units were shown to be effective protein stabilizers, preventing aggregation and prolonging activity. Herein, we report the synthesis and characterization of four trehalose regioisomers containing a vinylbenzyl ether moiety at either the 2-O, 3-O, 4-O, or 6-O position. Computational analysis of these regioisomers suggested that they differ in their conformational flexibility, but all retained the native clam shell conformation of trehalose. Polymers were synthesized from the monomers separately via free radical polymerization and one polymer was prepared containing all of the regioisomers. The polymers were tested for their ability to stabilize insulin, and were found to prevent agitation-induced aggregation comparably. The results show that for insulin the effect of trehalose positional modification is minimal and suggest that the clam shell conformation itself may be more important than the polymer backbone attachment site for stabilization of proteins.

This work presents a novel fabrication method for submicron to micro size textures on flat surfaces using the backside patterned texturing (BPT). The proposed method utilizes the pre-fabricated macro-features on the backside of work material, and thereafter the front side is face turned with a single point diamond tool to generate textured surfaces. Different from existing texturing methods, BPT produces textured surfaces from submicron to micro scale without any external gadgets such as vibration assisted machining or synchronized tool-spindle motion. The miniature feature arises on the diamond turned surface due to the induced residual stresses when the specimen is unleashed from the machine. To demonstrate the efficacy of the method, a series of machining experiments were conducted to fabricate various types of freeform surface textures like water-drop freeform, cylindrical freeform surfaces, etc. The fabrication methodology of different sizes of bumps with precisely controlled surface quality is illustrated. The texture profiles comprising the deformation height from hundreds of nanometer to few micrometers with mirror surface quality were successfully fabricated on the diamond machined surface. The experimental results suggest that the pre-fabricated pattern, workpiece thickness and machining condition play a critical role to determine the final shape and geometry of generated textures. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version

The dynamics of machine tools are greatly dependent on joints, since they add flexibility and damping to structures. In this study, the linear stiffness and damping of a joint in the transverse direction are obtained using two different methods: the inverse receptance coupling method and the new analytical joint identification (AJI) approach. The former approach finds the joint frequency response function by determining the difference between the response of the assembled structure and those of the substructures. However, the only required data for the AJI method are modal parameters of the assembled structure, which can be measured using experimental modal analysis. The accuracy of these methods is first investigated using numerical simulations. Experiments are then conducted on a structure consisting of two beams attached to one another in a lap joint. The proposed methods are utilized to experimentally extract the joint parameters in the transverse direction. Finally, the effects of varying the joint conditions, including surface roughness and the addition of interfacial materials, are investigated.

We derived a new analytic physical model for describing the temperature-dependent dielectric permittivities ee(T) and eo(T) in anisotropic mesophase molecules of nematic liquid crystals (NLCs). These temperature-dependent dielectric properties of NLCs could be explained by a six-parameter dielectric permittivity model, where the analytic dielectric permittivity curves of ee(T), eo(T), and Δe(T) from the model using the six parameters e*, Ae, Be, (Δe)o, λe, and T* showed excellent agreement with experimental data. The six-parameter dielectric permittivity model was compared to the conventional four-parameter refractive index model. To systematically investigate the temperature-dependent properties of the refractive indices (ne(T) and no(T)) and dielectric permittivities according to the molecular structure of the NLCs, four similar types of fluorinated phenyl bicyclohexane NLCs were selected. Using the presented models, the temperature-dependent behaviour of these four fluorinated NLCs was discussed, according to the molecular length of the alkyl chains and the positions of the fluorine substituents. In particular, two fitting equations for the temperature-dependent properties of threshold voltage and splay elastic LC constant could also be developed using the physical coefficients extracted from the six-parameter dielectric permittivity model, and these equations coincided well with experimental results.