Laser Scheme for Doppler Cooling of the Hydroxyl Cation (OH+).

We report on a cycling scheme for Doppler cooling of trapped OH+ ions using transitions between the electronic ground state X3Σ- and the first excited triplet state A3Π. We have identified relevant transitions for photon cycling and repumping, have found that coupling into other electronic states is strongly suppressed, and have calculated the number of photon scatterings required to cool OH+ to a temperature where Raman sideband cooling can take over. In contrast to the standard approach, where molecular ions are sympathetically cooled, our scheme does not require co-trapping of another species and opens the door to the creation of pure samples of cold molecular ions with potential applications in quantum information, quantum chemistry, and astrochemistry. The laser cooling scheme identified for OH+ is efficient despite the absence of near-diagonal Franck-Condon factors, suggesting that broader classes of molecules and molecular ions are amenable to laser cooling than commonly assumed.

Development of a bioactive tunable hyaluronic-protein bioconjugate hydrogel for tissue regenerative applications.

Every year, there are approximately 500 000 peripheral nerve injury (PNI) procedures due to trauma in the US alone. Autologous and acellular nerve grafts are among current clinical repair options; however, they are limited largely by the high costs associated with donor nerve tissue harvesting and implant processing, respectively. Therefore, there is a clinical need for an off-the-shelf nerve graft that can recapitulate the native microenvironment of the nerve. In our previous work, we created a hydrogel scaffold that incorporates mechanical and biological cues that mimic the peripheral nerve microenvironment using chemically modified hyaluronic acid (HA). However, with our previous work, the degradation profile and cell adhesivity was not ideal for tissue regeneration, in particular, peripheral nerve regeneration. To improve our previous hydrogel, HA was conjugated with fibrinogen using Michael-addition to assist in cell adhesion and hydrogel degradability. The addition of the fibrinogen linker was found to contribute to faster scaffold degradation via active enzymatic breakdown, compared to HA alone. Additionally, cell count and metabolic activity was significantly higher on HA conjugated fibrinogen compared previous hydrogel formulations. This manuscript discusses the various techniques deployed to characterize our new modified HA fibrinogen chemistry physically, mechanically, and biologically. This work addresses the aforementioned concerns by incorporating controllable degradability and increased cell adhesivity while maintaining incorporation of hyaluronic acid, paving the pathway for use in a variety of applications as a multi-purpose tissue engineering platform.

Caring for Refugees with Mental Health Problems: Difficulties Encountered by Providers Requesting Exemptions from United States Citizenship Examinations.

Mental health providers caring for refugees should be aware that obtaining citizenship is critical to stability and safety for their patients. In the United States (U.S.), obtaining citizenship requires applicants to pass an examination exhibiting working knowledge of English and foundational knowledge of U.S. civics. For refugees with mental health disorders that impair cognition, this may present insurmountable barriers. The United States Customs and Immigration Services (USCIS) offers form N-648 to request exemption from these requirements. However, the form can be difficult to complete in a manner acceptable to USCIS. In this paper, the authors present preliminary data on citizenship-related mental health evaluations and subsequent applications for 40 patients seen in a university-based refugee mental health clinic. We simplify the process into three phases, and present three cases highlighting specific complexities involved. Our experiences and recommendations may help other mental health providers prepare to advocate for their refugee patients.

Deriving instrumental point spread functions from partially occulted images.

The point spread function (PSF) of an imaging system describes the response of the system to a point source. Accurately determining the PSF enables one to correct for the combined effects of focusing and scattering within the imaging system and, thereby, enhance the spatial resolution and dynamic contrast of the resulting images. We present a semi-empirical semi-blind methodology to derive a PSF from partially occulted images. We partition the two-dimensional PSF into multiple segments, set up a multilinear system of equations, and directly fit the system of equations to determine the PSF weight in each segment. The algorithm is guaranteed to converge toward the correct instrumental PSF for a large class of occultations, does not require a predefined functional form of the PSF, and can be applied to a large variety of partially occulted images, such as within laboratory settings, regular calibrations within a production line or in the field, astronomical images of distant clusters of stars, or partial solar eclipse images. We show that the central weight of the PSF, which gives the percentage of photons that are not scattered by the instrument, is accurate to better than 1.2%. The mean absolute percentage error between the reconstructed and true PSF is usually between 0.5 and 5% for the entire PSF, between 0.5 and 5% for the PSF core, and between 0.5 and 3% for the PSF tail.

Atomic-Scale View of Protein-PEG Interactions that Redirect the Thermal Unfolding Pathway of PEGylated Human Galectin-3.

PEGylation is a promising approach to address the central challenge of applying biologics, i.e., lack of protein stability in the demanding environment of the human body. Wider application is hindered by lack of atomic level understanding of protein-PEG interactions, preventing design of conjugates with predicted properties. We deployed an integrative structural and biophysical approach to address this critical challenge with the PEGylated carbohydrate recognition domain of human galectin-3 (Gal3C), a lectin essential for cell adhesion and potential biologic. PEGylation dramatically increased Gal3C thermal stability, forming a stable intermediate and redirecting its unfolding pathway. Structural details revealed by NMR pointed to a potential role of PEG localization facilitated by charged residues. Replacing these residues subtly altered the protein-PEG interface and thermal unfolding behavior, providing insight into rationally designing conjugates while preserving PEGylation benefits.

Laser Probing of the Rotational Cooling of Molecular Ions by Electron Collisions.

We present state-selected measurements of rotational cooling and excitation rates of CH^{+} molecular ions by inelastic electron collisions. The experiments are carried out at a cryogenic storage ring, making use of a monoenergetic electron beam at matched velocity in combination with state-sensitive laser dissociation of the CH^{+} ions for simultaneous monitoring of the rotational level populations. Employing storage times of up to 600 s, we create conditions where electron-induced cooling to the J=0 ground state dominates over radiative relaxation, allowing for the experimental determination of inelastic electron collision rates to benchmark state-of-the-art theoretical calculations. On a broader scale, our experiments pave the way to probe inelastic electron collisions for a variety of molecular ions relevant in various plasma environments.

Ion energy distribution in an electron beam ion trap inferred from simulations of the trapped ion cloud.

We have inferred the energy distribution of trapped ions in an electron beam ion trap (EBIT) from simulations of the spatial distribution of Fe^{13+} ions and a comparison with measured visible light images of the ion cloud. We simulated the cloud of Fe^{13+} ions by computing ion trajectories in the EBIT for different ion energy distributions used to initialize the trajectories. We then performed a least-squares fit to infer the ion energy distribution that best reproduced the measured ion cloud. These best-fit distributions were typically non-Maxwellian. For electron beam energies of 395-475 eV and electron beam currents of 1-9 mA, we find that the average ion energy is in the range of 10-300 eV. We also find that the average ion energy increases with increasing beam current approximately as 〈E〉≈25I_{e}eV, where I_{e} is the electron beam current in mA. We have also compared our results to Maxwell-Boltzmann-distribution ion clouds. We find that our best-fit non-thermal distributions have an 〈E〉 that is less than half that of the T from the best-fit Maxwell-Boltzmann distributions (〈E〉/q)/T=0.41±0.05.

Recyclable & highly porous organo-aerogel adsorbents from biowaste for organic contaminants' removal.

Selective aerogel has become an attractive adsorbent for removing oil and organic contaminants due to its low density and excellent adsorption capacity. However, aerogels usually use non-sustainable or expensive nanomaterials and require complicated fabrication processes. Herein, using low-cost lignin reclaimed from the biorefinery waste stream as the starting material, we fabricated a highly porous, mechanically strong, and stable aerogel via a simple and one-step method under mild conditions. This aerogel exhibits a controllable micropore structure and achieves quick and efficient adsorption for oil (435% g/g), as well as toxic solvents such as THF (365% g/g). The selective and stable adsorbent can be reused multiple times and the oil adsorption capacity after 5 cycles remained at 89%. This highly efficient, mechanically strong, stable, and regenerable aerogel is a potential candidate for multiple applications such as cleaning up organic contaminants, oil remediation, and oil/water separation. Meanwhile, it also employs a "waste-treat-waste" concept by adding extra value to the biorefinery process for high-efficiency circular bioeconomy.

Glycerol-Based Dendrimer Nanocomposite Film as a Tunable pH-Sensor for Food Packaging.

Large amounts of food are wasted during the food supply chain. This loss is in part due to consumer confusion over dates on food packages that can indicate a variety of quality indicators in the product (e.g., expiration date, "best by" date, "sell by" dates, etc.). To reduce this food loss, much research has been focused on the films that offer simple and easily manipulated indication systems to detect food spoilage. However, these materials are usually hydrophilic biopolymers that can detect the food spoilage in a wide pH range but do not provide highly sensitive real-time measurements. In this work, a glycerol-based nanocomposite core-shell latex film was synthesized to create a responsive packaging material that can provide real-time pH detection of food with high sensitivity. First, the pH-responsive dendrimer comonomer was synthesized from glycerol and diamine. Then, the nanoencapsulation polymerization process via miniemulsion was conducted to form a core-shell structure with tunable nanoshell thickness for a sensible pH-responsive release (<0.5 pH change). Next, the flexible film encapsulated a color-indicative dye that provided highly sensitive and visible color changes as both the pH dropped and the time elapsed in the food. This film also provided a barrier to water and heat and resisted deformation. Ultimately, this nanocomposite flexible film pending a pH sensor has the potential as an intelligent food packaging material for a universal, accurate, easy-to-use, and real-time food spoilage monitoring system to reduce food waste.

Allomelanin: A Biopolymer of Intrinsic Microporosity.

Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find artificial allomelanin analogues exhibit high intrinsic microporosity and describe an approach for further increasing and tuning that porosity. Notably, the synthetic method involves an oxidative polymerization of 1,8-DHN in water, negating the need for multiple complex templating steps and avoiding expensive or complex chemical precursors. The well-defined morphologies of these nanomaterials were elucidated by a combination of electron microscopy and scattering methods, yielding to high-resolution 3D reconstruction based on small-angle X-ray scattering (SAXS) results. Synthetic allomelanin nanoparticles exhibit high BET areas, up to 860 m2/g, and are capable of ammonia capture up to 17.0 mmol/g at 1 bar. In addition, these nanomaterials can adsorb nerve agent simulants in solution and as a coating on fabrics with high breathability where they prevent breakthrough. We also confirmed that naturally derived fungal melanin can adsorb nerve gas simulants in solution efficiently despite lower porosity than synthetic analogues. Our approach inspires further analysis of yet to be discovered biological materials of this class where melanins with intrinsic microporosity may be linked to evolutionary advantages in relevant organisms and may in turn inspire the design of new high surface area materials.

Entrepreneurship in Polymer Chemistry.

Launching a startup company is like synthesizing a new molecule. There is a starting point and a general concept for how to achieve the desired end. Known steps may be taken, but a successful synthesis is rarely the result of the original plan and relies on perseverance and creativity. If done well, the starting molecule (idea) gives rise to a new final product (business). Having personally lived these journeys, the authors of this viewpoint distilled their combined experiences into relevant topics for scientific entrepreneurs. This viewpoint is not a how-to guide for launching a startup. Instead, relatable personal insights and potential best practices are shared to catalyze discussions around a topic of growing relevance to both the polymer community and workforce of the future.

Experimental study of the proton-transfer reaction C + H2+ → CH+ + H and its isotopic variant (D2+).

We report absolute integral cross section (ICS) measurements using a dual-source merged-fast-beams apparatus to study the titular reactions over the relative translational energy range of Er ∼ 0.01-10 eV. We used photodetachment of C- to produce a pure beam of atomic C in the ground electronic 3P term, with statistically populated fine-structure levels. The H2+ and D2+ were formed in an electron impact ionization source, with well known vibrational and rotational distributions. The experimental work is complemented by a theoretical study of the CH2+ electronic system in the reactant and product channels, which helps to clarify the possible reaction mechanisms underlying the ICS measurements. Our measurements provide evidence that the reactions are barrierless and exoergic. They also indicate the apparent absence of an intermolecular isotope effect, to within the total experimental uncertainties. Capture models, taking into account either the charge-induced dipole interaction potential or the combined charge-quadrupole and charge-induced dipole interaction potentials, produce reaction cross sections that lie a factor of ∼4 above the experimental results. Based on our theoretical study, we hypothesize that the reaction is most likely to proceed adiabatically through the 14A' and 14A'' states of CH2+via the reaction C(3P) + H2+(2Σ+g) → CH+(3Π) + H(2S). We also hypothesize that at low collision energies only H2+(v ≤ 2) and D2+(v ≤ 3) contribute to the titular reactions, due to the onset of dissociative charge transfer for higher vibrational v levels. Incorporating these assumptions into the capture models brings them into better agreement with the experimental results. Still, for energies ⪅0.1 eV where capture models are most relevant, the modified charge-induced dipole model yields reaction cross sections with an incorrect energy dependence and lying ∼10% below the experimental results. The capture cross section obtained from the combined charge-quadrupole and charge-induced dipole model better matches the measured energy dependence but lies ∼30-50% above the experimental results. These findings provide important guidance for future quasiclassical trajectory and quantum mechanical treatments of this reaction.

Modular Genetic Code Expansion Platform and PISA Yield Well-Defined Protein-Polymer Assemblies.

We present a modular platform from which biohybrid protein-polymer nanostructures can be generated in a straightforward and facile manner. Specifically, an aqueous polymerization-induced self-assembly (PISA) AB block copolymerization system was derived from a mutant superfolder green fluorescent protein (sfGFP) as the solvophilic, stabilizing A block. By genetically encoding sfGFP with an isobutyryl bromide functionality, we grafted a quintessential atom-transfer radical polymerization initiation site with hydroxypropyl methacrylate (HPMA) to form the solvophobic B block. Monitoring nanostructure formation using dynamic light scattering, gel permeation chromatography, and transmission electron microscopy revealed uniform micellar morphologies. The radii of the micelles increased with increasing HPMA block length, resulting in nanoparticle sizes ranging from 15 to 48 nm. Solvophilic stabilization afforded by the encoded sfGFP makes this an ideal PISA initiator, and we posit this platform has potential for generating complex biohybrid nanostructures for other protein-polymer systems.

Darunavir-Resistant HIV-1 Protease Constructs Uphold a Conformational Selection Hypothesis for Drug Resistance.

Multidrug resistance continues to be a barrier to the effectiveness of highly active antiretroviral therapy in the treatment of human immunodeficiency virus 1 (HIV-1) infection. Darunavir (DRV) is a highly potent protease inhibitor (PI) that is oftentimes effective when drug resistance has emerged against first-generation inhibitors. Resistance to darunavir does evolve and requires 10-20 amino acid substitutions. The conformational landscapes of six highly characterized HIV-1 protease (PR) constructs that harbor up to 19 DRV-associated mutations were characterized by distance measurements with pulsed electron double resonance (PELDOR) paramagnetic resonance spectroscopy, namely double electron-electron resonance (DEER). The results show that the accumulated substitutions alter the conformational landscape compared to PI-naïve protease where the semi-open conformation is destabilized as the dominant population with open-like states becoming prevalent in many cases. A linear correlation is found between values of the DRV inhibition parameter Ki and the open-like to closed-state population ratio determined from DEER. The nearly 50% decrease in occupancy of the semi-open conformation is associated with reduced enzymatic activity, characterized previously in the literature.

Toxicity assessment of a novel oil dispersant based on silica nanoparticles using Fathead minnow.

Oil spill accidents are a major concern for aquatic organisms. In recent history, the Deepwater Horizon blowout spilled 500 million liters of crude oil into the Gulf of Mexico. Corexit 9500A was used to disperse the oil since it was the method approved at that time, despite safety concerns about its use. A better solution is necessary for dispersing oil from spills that reduces the toxicity to exposed aquatic organisms. To address this challenge, novel engineered nanoparticles were designed using silica cores grafted with hyperbranched poly(glycidol) branches. Because the silica core and polymers are known to be biocompatible, we hypothesized that these particles are nontoxic to fathead minnows (Pimephales promelas) and would decrease their exposure to oil polyaromatic hydrocarbons. Fathead minnow embryos, juveniles and adult stages were exposed to the particles alone or in combination with a water-accommodated fraction of oil. Acute toxicity of nanoparticles to fish was tested by measuring mortality. Sub-lethal effects were also measured including gene expression of cytochrome P450 1a (cyp1a) mRNA and heart rate in embryos. In addition, a mixture of particles plus the water-accommodated fraction was directly introduced to adult female fathead minnows by gavage. Three different nanoparticle concentrations were used (2, 10, and 50 mg/L) in either artificial fresh water or the water-accommodated fraction of the oil. In addition, nanoparticle-free controls were carried out in the two solutions. No significant mortality was observed for any age group or nanoparticle concentration, suggesting the safety of the nanoparticles. In the presence of the water-accommodated fraction alone, juvenile and adult fathead minnows responded by increasing expression of cyp1a. The addition of nanoparticles to the water-accommodated fraction reduced cyp1a gene expression in treatments. Heart rate was also restored to normal parameters in embryos co-exposed to nanoparticles and to the water-accommodated fraction. Measurement of polyaromatic hydrocarbons confirmed their presence in the tested solutions and the reduction of available PAH in WAF treated with the nanoparticles. Our findings suggest the engineered nanoparticles may be protecting the fish by sequestering polyaromatic hydrocarbons from oil, measured indirectly by the induction of cypa1 mRNAs. Furthermore, chemical analysis showed a reduction in PAH content in the water accommodated fraction with the presence of nanoparticles.

Synthesis and Characterization of a Leucine-Based Block Co-Polypeptide: The Effect of the Leucine Zipper on Self-Assembly.

The self-assembly behavior of an ABC triblock copolypeptide consisting of poly(ethylene oxide-b-(leucine-s-valine)-b-lysine) (PEO-PLV-PK) was examined via dynamic light scattering in dilute aqueous solution. Leucine is a hydrophobic, α-helix forming polypeptide that exhibits a "zipper effect" in coiled-coil dimers. We hypothesize that the specific interaction afforded by the leucine zipper dominates the thermodynamics of self-assembly through the side-by-side ordering of α-helices, which drives vesicle formation in a polymer with only 6 wt % hydrophobic content. Additionally, a multitude of assembly sizes and morphologies were attainable from a single polymer, depending on the solution processing method. Thermodynamic effects of the leucine zipper can be interpreted, in part, from solubility parameters determined from molecular modeling. The combination of synthesis, solvent processing, and computational studies helps to elucidate the thermodynamic effects of this unique assembly motif on classical self-assembly processes.

Hierarchical Fractal Assemblies from Poly(ethylene oxide- b-lysine- b-leucine).

Poly(ethylene oxide43- b-lysine62- b-leucine72) (wherein subscripts denote the degree of polymerization) was synthesized via ring-opening polymerization of N-carboxyanhydrides using an amine-terminated poly(ethylene oxide) macroinitiator, with polypeptide blocks produced by sequential monomer addition. Infrared and circular dichroism spectroscopy indicated that the peptide blocks in this polymer formed α-helices in the solid and solution states, respectively. In the aqueous solution, this polymer self-assembled into spherical micelles with a hydrodynamic radius of approximately 90 nm at concentrations between 0.05 and 0.20% w/w and pH values between 2 and 6.5. Upon preparation of transmission electron microscopy (TEM) grids, the micelles at pH 2 underwent hierarchical assembly to produce fractal assemblies, whereas small clusters were observed for micellar solutions at pH 6.5. Cryogenic-TEM of solutions showed spherical micelles, and dynamic light scattering showed no large (∼1 µm) aggregates in the solution, which suggests that fractal formation was a result of the drying process, and that fractals were not present in the solution. This system provides a facile route to nanostructured surfaces, which can be used for applications such as modulating cell adhesion or promoting the growth of neurons.

Learning from Our Patients: Training Psychiatry Residents in Refugee Mental Health.

OBJECTIVE: Psychiatric residents are increasingly called upon to work cross-culturally, serving diverse populations including refugees. This study aims to (1) understand the training experience of psychiatry residents working with refugees and (2) assess the level of satisfaction of refugees, most of whom are Iraqi, who seek psychological treatment at the University of Colorado Hospital (UCH)'s Refugee Mental Health Program of Colorado (RMHPC). METHODS: Using qualitative methodology, over a 1-year period, independent evaluators interviewed a group of nine residents who chose to participate in an RMHPC elective and also interviewed ten Iraqi refugee patients who sought services at the clinic. Recordings of the interviews were transcribed and analyzed using thematic analysis. Emerging themes were identified for both resident and refugee patient interviews. RESULTS: Five major themes emerged summarizing residents' experiences: (1) adapting practices to meet refugee needs, (2) value of supervision, (3) cultural barriers, (4) need for extra resources, and (5) effect on future practice. Four major themes emerged summarizing Iraqi refugees' experiences: (1) reasons for seeking treatment, (2) barriers to treatment, (3) residents' knowledge of culture and needs, and (4) quality of treatment. CONCLUSIONS: This study's findings highlight the complexities of effectively treating refugee patients and suggest ideas for training residents. Additionally, they offer important frameworks for developing, implementing, and evaluating culturally responsive practices in the context of training psychiatry residents and other mental health professionals. An essential key to this process was giving voice to refugees who accessed and engaged our services.

Quantitative relationship between cavitation and shear rheology.

Cavitation rheology is a powerful, simple, and inexpensive technique to study the moduli of polymer gels, however its use has not yet become widespread because few studies to date have directly compared this technique to traditional oscillatory shear rheology. Herein, we report a quantitative relationship between the gel modulus determined using cavitation and shear rheology for three series of model gels whose networks are composed of (1) permanently covalent, (2) dynamic-covalent, and (3) physical hydrogen-bond crosslinks. We determine a simple proportionality constant that allows for conversion of the moduli obtained from both types of experiments and is highly dependent on the bond energy responsible for gelation. This study provides a framework for researchers in a broad range of disciplines who can exploit the ease of cavitation rheology and place their results in the context of traditional oscillatory shear rheology.