Controlling the electro-optic response of a semiconducting perovskite coupled to a phonon-resonant cavity.

Optical cavities, resonant with vibrational or electronic transitions of material within the cavity, enable control of light-matter interaction. Previous studies have reported cavity-induced modifications of chemical reactivity, fluorescence, phase behavior, and charge transport. Here, we explore the effect of resonant cavity-phonon coupling on the transient photoconductivity in a hybrid organic-inorganic perovskite. To this end, we measure the ultrafast photoconductivity response of perovskite in a tunable Fabry-Pérot terahertz cavity, designed to be transparent for optical excitation. The terahertz-cavity field-phonon interaction causes apparent Rabi splitting between the perovskite phonon mode and the cavity mode. We explore whether the cavity-phonon interaction affects the material's electron-phonon interaction by determining the charge-carrier mobility through photoconductivity. Despite the apparent hybridization of cavity and phonon modes, we show that the perovskite properties in both ground (phonon response) and excited (photoconductive response) states remain unaffected by the tunable light-matter interaction. Yet the response of the integral perovskite-terahertz optical cavity system depends critically on the interaction strength of the cavity with the phonon: the transient terahertz response to optical excitation can be increased up to threefold by tuning the cavity-perovskite interaction strength. These results enable tunable switches and frequency-controlled induced transparency devices.

An exploratory study on functional connectivity after mild traumatic brain injury: Preserved global but altered local organization.

INTRODUCTION: This study aimed to investigate alterations in whole-brain functional connectivity after a concussion using graph-theory analysis from global and local perspectives and explore the association between changes in the functional network properties and cognitive performance. METHODS: Individuals with mild traumatic brain injury (mTBI, n = 29) within a month after injury, and age- and sex-matched healthy controls (n = 29) were included. Graph-theory measures on functional connectivity assessed using resting state functional magnetic resonance imaging data were acquired from each participant. These included betweenness centrality, strength, clustering coefficient, local efficiency, and global efficiency. Multi-domain cognitive functions were correlated with the graph-theory measures. RESULTS: In comparison to the controls, the mTBI group showed preserved network characteristics at a global level. However, in the local network, we observed decreased betweenness centrality, clustering coefficient, and local efficiency in several brain areas, including the fronto-parietal attention network. Network strength at the local level showed mixed-results in different areas. The betweenness centrality of the right parahippocampus showed a significant positive correlation with the cognitive scores of the verbal learning test only in the mTBI group. CONCLUSION: The intrinsic functional connectivity after mTBI is preserved globally, but is suboptimally organized locally in several areas. This possibly reflects the neurophysiological sequelae of a concussion. The present results may imply that the network property could be used as a potential indicator for clinical outcomes after mTBI.

Robot-assisted gait training with auditory and visual cues in Parkinson's disease: A randomized controlled trial.

BACKGROUND: Robot-assisted gait training (RAGT) may have beneficial effects on Parkinson's disease (PD); however, the evidence to date is inconsistent. OBJECTIVES: This study compared the effects of RAGT and treadmill training (TT) on gait speed, dual-task gait performance, and changes in resting-state brain functional connectivity in individuals with PD. METHODS: In this prospective, single-center, randomized controlled trial with a parallel two-group design, 44 participants were randomly allocated to undergo 12 sessions (3 times per week for 4 weeks) of RAGT or TT. The primary outcome was gait speed on the 10-m walk test (10mWT) under comfortable walking conditions. Secondary outcomes included dual-task interference on gait speed, balance, disability scores, fear of falling, freezing of gait, and brain functional connectivity changes. All clinical outcomes were measured before (T0), immediately after (T1), and 1 month after treatment (T2). RESULTS: The mean (SD) age of the participants was 68.1 (8.1) years, and mean disease duration 108.0 (61.5) months. The groups did not significantly differ on the 10mWT (T0-T1, p = 0.726, Cohen's d = 0.133; T0-T2, p = 0.778, Cohen's d = 0.121). We observed a significant time-by-group interaction (F = 3.236, p = 0.045) for cognitive dual-task interference, controlling for confounders. After treatment, coupling was decreased to a greater extent with RAGT than TT between the visual and dorsal attention networks (p = 0.015), between bilateral fronto-parietal networks (p = 0.043), and between auditory and medial temporal networks (p = 0.018). Improvement in cognitive dual-task interference was positively correlated with enhanced visual and medial temporal network coupling overall (r = 0.386, p = 0.029) and with TT (r = 0.545, p = 0.024) but not RAGT (r = 0.151, p = 0.590). CONCLUSIONS: RAGT was not superior to intensity-matched TT on improving gait functions in individuals with PD but may be beneficial in improving gait ability under cognitive dual-task conditions. The therapeutic mechanism and key functional connectivity changes associated with improvement may differ between treatment strategies. CLINICALTRIALS: GOV: #NCT03490578.

Effects of gait training on structural brain changes in Parkinson's disease.

BACKGROUND: Gait training may lead to functional brain changes in Parkinson's disease (PD); however, there is a lack of studies investigating structural brain changes after gait training in PD. OBJECTIVE: To investigate structural brain changes induced by 4 weeks of gait training in individuals with PD. METHODS: Diffusion tensor imaging and structural T1 images were acquired in PD group before and after robot-assisted gait training or treadmill training, and in healthy control group. Tract-based spatial statistics and tensor-based morphometry were conducted to analyze the data. The outcome of gait training was assessed by gait speed and dual-task interference of cognitive or physical tests of the 10-meter walking test representing gait automaticity. The associations between structural brain changes and these outcomes were investigated using correlation analysis. RESULTS: A total of 31 individuals with PD (68.5±8.7 years, the Hoehn & Yahr stage of 2.5 or 3) and 28 healthy controls (66.6±8.8 years) participated in this study. Compared to the controls, PD group at baseline showed a significant increased fractional anisotropy (FA) in the right forceps minor and bilateral brainstem and reduced radial diffusivity (RD) in the right superior longitudinal fasciculus, as well as the expanded structural volumes in the several brain areas. After gait training, FA increased in the left internal capsule and it decreased in the left cerebellum Crus I, while the structural volume did not change. The increased FA in the left internal capsule positively correlated with the baseline gait speed and negatively correlated with gait speed improvement; moreover, the decreased FA in the left cerebellum Crus I negatively correlated with the baseline gait speed during the cognitive task. CONCLUSIONS: Gait training induces white matter changes in the brain of individuals with PD, which suggests the improvement of brain structural pathology to mitigate the impact of neurodegenerative consequences.

Theoretical analysis of glide-Z2 magnetic topological photonic crystals.

Gapped systems with glide symmetry can be characterized by a Z2 topological invariant. We study the magnetic photonic crystal with a gap between the second and third lowest bands, which is characterized by the nontrivial glide-Z2 topological invariant that can be determined by symmetry-based indicators. We show that under the space group No. 230 (I a3¯d), the topological invariant is equal to a half of the number of photonic bands below the gap. Therefore, the band gap between the second and third lowest bands is always topologically nontrivial, and to realize the topological phase, we need to open a gap for the Dirac point at the P point by breaking time-reversal symmetry. With staggered magnetization, the photonic bands are gapped and the photonic crystal becomes topological, whereas with uniform magnetization, a gap does not open, which can be attributed to the minimal band connectivity exceeding two in this case. By introducing the notion of Wyckoff positions, we show how the topological characteristics are determined from the structure of the photonic crystals.

Low-field onset of Wannier-Stark localization in a polycrystalline hybrid organic inorganic perovskite.

Methylammonium lead iodide perovskite (MAPbI3) is renowned for an impressive power conversion efficiency rise and cost-effective fabrication for photovoltaics. In this work, we demonstrate that polycrystalline MAPbI3s undergo drastic changes in optical properties at moderate field strengths with an ultrafast response time, via transient Wannier Stark localization. The distinct band structure of this material - the large lattice periodicity, the narrow electronic energy bandwidths, and the coincidence of these two along the same high-symmetry direction - enables relatively weak fields to bring this material into the Wannier Stark regime. Its polycrystalline nature is not detrimental to the optical switching performance of the material, since the least dispersive direction of the band structure dominates the contribution to the optical response, which favors low-cost fabrication. Together with the outstanding photophysical properties of MAPbI3, this finding highlights the great potential of this material in ultrafast light modulation and novel photonic applications.

Cognitive Training Using Fully Immersive, Enriched Environment Virtual Reality for Patients With Mild Cognitive Impairment and Mild Dementia: Feasibility and Usability Study.

BACKGROUND: Cognitive training using virtual reality (VR) may result in motivational and playful training for patients with mild cognitive impairment and mild dementia. Fully immersive VR sets patients free from external interference and thus encourages patients with cognitive impairment to maintain selective attention. The enriched environment, which refers to a rich and stimulating environment, has a positive effect on cognitive function and mood. OBJECTIVE: The aim of this study was to investigate the feasibility and usability of cognitive training using fully immersive VR programs in enriched environments with physiatrists, occupational therapists (OTs), and patients with mild cognitive impairment and mild dementia. METHODS: The VR interface system consisted of a commercialized head-mounted display and a custom-made hand motion tracking module. We developed the virtual harvest and cook programs in enriched environments representing rural scenery. Physiatrists, OTs, and patients with mild cognitive impairment and mild dementia received 30 minutes of VR training to evaluate the feasibility and usability of the test for cognitive training. At the end of the test, the usability and feasibility were assessed by a self-report questionnaire based on a 7-point Likert-type scale. Response time and finger tapping were measured in patients before and after the test. RESULTS: Participants included 10 physiatrists, 6 OTs, and 11 patients with mild cognitive impairment and mild dementia. The mean scores for overall satisfaction with the program were 5.75 (SD 1.00) for rehabilitation specialists and 5.64 (SD 1.43) for patients. The response time of the dominant hand in patients decreased after the single session of cognitive training using VR, but this was not statistically significant (P=.25). There was no significant change in finger tapping in either the right or left hand (P=.48 and P=.42, respectively). None of the participants reported headaches, dizziness, or any other motion sickness after the test. CONCLUSIONS: A fully immersive VR cognitive training program may be feasible and usable in patients with mild cognitive impairment and mild dementia based on the positive satisfaction and willingness to use the program reported by physiatrists, OTs, and patients. Although not statistically significant, decreased response time without a change in finger tapping rate may reflect a temporary increase in attention after the test. Additional clinical trials are needed to investigate the effect on cognitive function, mood, and physical outcomes.

Effects of leucine-enriched essential amino acid supplementation on muscular fatigue and inflammatory cytokines in wheelchair basketball players.

PURPOSE: This study aimed to investigate the effects of leucine-enriched essential amino acid (LEAA) supplementation on muscle fatigue and the level of inflammatory cytokines in wheelchair basketball players after a basketball game and interval training. METHODS: Of the ten recruited wheelchair basketball players (aged 34.5±8.9 years; lean body mass of 34.3±10.0 kg) who had spinal cord injury (SCI) and had undergone amputation, nine participated in the final test. These nine athletes received LEAA supplements (3 times 4.0 g/day) or placebo treatment in a double-blind, randomized, crossover study. We measured variables related to muscular fatigue and inflammatory response before the intense exercise and 4 days after recovery. RESULTS: The significant effect of LEAA supplementation was inhibition of circulating IL-6 levels in the LEAA-treated group compared with the placebo group (P < .05). However, no changes were observed in the TNF-α and creatinine kinase levels. Moreover, analysis of variance analysis showed no significant difference in the relative values of muscle soreness. However, the effect size analysis with Cohen's d reported a significant improvement in the relative values of whole body and back muscle soreness. CONCLUSION: Our results revealed that LEAA supplementation before and after intense exercise could help reduce muscle soreness and IL-6 levels in wheelchair basketball players.

Effects of 8-week Pilates training program on hamstring/quadriceps ratio and trunk strength in adolescent baseball players: a pilot case study.

The purpose of this pilot case study is to investigate the effects of Pilates training on hamstring/quadriceps ratio, trunk strength, shoulder strength, and body composition in adolescent baseball players. Eight adolescent baseball players, 15 years of age, participated in Pilates program (supervised training, 50 min per session for three times a week for 8 weeks) using reformer and Cadillac. The intensity of the program was progressively increased by applying beginner level for 1-2 weeks, intermediate level for 3-6 weeks, and advance level for 7-8 weeks. To verify the effect of the Pilates program on hamstring/quadriceps ratio, trunk strength, shoulder strength and body composition, participants performed bioelectrical impedance analysis and isokinetic testing at pre- and posttraining. After the Pilates training, there were significant increases in body weight (P<0.01), left arm muscle mass (P<0.01), and trunk muscle mass (P<0.01). In addition, there were significant increases in left and right knee flexion peak torque (P<0.01 and P<0.05, respectively), right knee extension peak torque (P<0.05), left and right hamstring/quadriceps ratio (both P<0.01), trunk flexion peak torque (P<0.05) and shoulder flexion peak torque (P<0.05) after 8 weeks of training. Therefore, Pilates training increased muscle mass, hamstring/quadriceps ratio, trunk and shoulder strength, suggesting that it may help baseball players do better performance and prevent future injuries in adolescent players.

Tunable modulation of antibody-antigen interaction by protease cleavage of protein M.

While immunoglobulins find ubiquitous use in biotechnology as static binders, recent developments have created proantibodies that enable orthogonal switch-like behavior to antibody function. Previously, peptides with low binding affinity have been genetically fused to antibodies, to proteolytically control binding function by blocking the antigen-binding site. However, development of these artificial blockers requires panning for peptide sequences that reversibly affect antigen affinity for each antibody. Instead, a more general strategy to achieve dynamic control over antibody affinity may be feasible using protein M (ProtM) from Mycoplasma genitalium, a newly identified polyspecific immunity evasion protein that is capable of blocking antigen binding for a wide range of antibodies. Using C-terminus truncation to identify ProtM variants that are still capable of binding to antibodies without the ability to block antigens, we developed a novel and universal biological switch for antibodies. Using a site-specifically placed thrombin cut site, antibody affinity can be modulated by cleavage of the two distinct antibody-binding and antigen-blocking domains of ProtM. Because of the high affinity of ProtM toward a large variety of IgG subtypes, this strategy may be used as a universal approach to create proantibodies that are conditionally activated by disease-specific proteases such as matrix metalloproteinases.

Removal of Surface Oxygen Vacancies Increases Conductance Through TiO2 Thin Films for Perovskite Solar Cells.

We report that UV-ozone treatment of TiO2 anatase thin films is an efficient method to increase the conductance through the film by more than 2 orders of magnitude. The increase in conductance is quantified via conductive scanning force microscopy on freshly annealed and UV-ozone-treated TiO2 anatase thin films on fluorine-doped tin oxide substrates. The increased conductance of TiO2 anatase thin films results in a 2% increase of the average power conversion efficiency (PCE) of methylammonium lead iodide-based perovskite solar cells. PCE values up to 19.5% for mesoporous solar cells are realized. The additional UV-ozone treatment results in a reduced number of oxygen vacancies at the surface, inferred from X-ray photoelectron spectroscopy. These oxygen vacancies at the surface act as charge carrier traps and hinder charge extraction from the adjacent material. Terahertz measurements indicate only minor changes of the bulk conductance, which underlines the importance of UV-ozone treatment to control surface-based defects.

Effects of aerobic exercise training on the risk factors for liver diseases in elderly women with obesity and impaired fasting glucose: A pilot study.

PURPOSE: In the present pilot study, we aimed to investigate the effects of the Silverrobics exercise program, which is similar to aerobic dance, on the factors related to glucose metabolism and liver enzymes. METHODS: Eight elderly women with obesity and impaired fasting glucose participated in the Silverrobics exercise program (60 minutes per session for five times a week for 8 weeks). The program was conducted at 50-60% of the heart rate reserve at 1 to 2 weeks and at 60-80% of the heart rate reserve at 3 to 8 weeks. To verify the effect of this 8-week exercise program on glucose metabolism and liver enzymes, blood analysis at pre- and post-training was performed. RESULTS: After the Silverrobics exercise program, there were significant decreases in the glucose (p<0.05), glycated hemoglobin A1c (p<0.05), 1,5-anhydroglucitol (p<0.05), and insulin levels (p<0.01) and homeostatic model assessment of insulin resistance score (p<0.05). However, there were no significant effects on the liver enzymes, except for alkaline phosphatase. The alkaline phosphatase level increased after the Silverrobics exercise program (p<0.05). CONCLUSION: Although the Silverrobics exercise program had no beneficial effects on the liver enzymes, it may play an important role in preventing liver diseases considering the effects on glucose metabolism.

Isolated hook of hamate fracture in sports that require a strong grip comprehensive literature review.

BACKGROUND: The aim of the study was to report characteristics of isolated hook of hamate fractures related to sports that require a strong grip and to identify factors affecting early diagnosis and recovery period. METHODS: A comprehensive literature search was conducted using MEDLINE, EMBASE, SCOPUS, Web of Science, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and the clinical trials registry and database of the US National Institutes of Health (ClinicalTrials.gov). There were no limits on the language or year of publication.This article included case reports and literature reviews for patients with isolated hook of hamate fractures related to sports that require a strong grip from 1977 to 2016.Two experienced reviewers extracted data from each study. The following data were extracted: sample size, patient's characteristics, cause of injury, injury side, time to diagnosis and symptoms, physical examination results, diagnostic work-up, treatment, complications, and recovery period. RESULTS: A total of 21 case reports and literature reviews with 120 patients satisfied our inclusion criteria. There was no significant difference in the time to diagnosis between the group before computed tomography (CT) was widely used and the group after CT was widely used. Recovery period showed a positive relationship with age (coefficient = 0.418, P < .01), time from injury to diagnosis or surgery (coefficient = 0.206, P < .05), and type of athlete (coefficient = 0.270, P < .01). On multiple stepwise regression analysis, recovery period was significantly associated with age (ß = 0.418, P = .00), but not with time from injury to diagnosis or surgery. CONCLUSIONS: Advance in diagnostic techniques does not guarantee early diagnosis of hook of hamate fractures. Strong suspicion of the disease with physical examination and carefully hearing patient's history are important for early diagnosis and management for patients with hook of hamate fractures.

Vibrational Coupling between Organic and Inorganic Sublattices of Hybrid Perovskites.

The interplay of electronic and nuclear degrees of freedom in semiconductor hybrid organic-inorganic perovskites determines many of their fundamental photophysical properties. For instance, charge carriers are dressed with phonons, that is, form polarons, and combination modes composed of strongly mixed localized vibrations and delocalized phonons can provide pathways for electronic energy relaxation and dissipation. Mixing of the different types of nuclear motion in vibrational combination modes requires their strong coupling. The direct measurement of coupling between the high-frequency N-H stretch modes of the organic methylammonium and formamidinium ions and low-frequency Pb-I phonon modes of the inorganic sub-lattice in hybrid organic-inorganic perovskites is presented. The results reveal direct and substantial coupling between the non-covalently interacting organic and inorganic sub-lattices.

Effect of Spatone Supplement on Endurance Capacity and Inflammatory Cytokines in a Rapid Weight Control Program in University Wrestlers: A Pilot Study.

In this pilot study, we investigated the effect of spatone, a naturally occurring mineral water supplement, on endurance capacity and inflammatory cytokines in wrestlers undergoing a rapid weight control program. Nine amateur university wrestlers participated and were randomly divided into placebo- and spatone-treated groups. The study used a crossover design, including a 4-week washout period. The rapid weight control program was focused on body weight loss, while maintaining their athletic performance (muscular strength and cardiovascular endurance). The initial body weight was 87.19 ± 2.45 kg in the spatone-treated group and 86.60 ± 3.01 kg in the placebo group. After the rapid weight control program, the body weight decreased to 83.56 ± 2.71 kg (4.21% decrease) in the spatone-treated group and 82.95 ± 2.97 kg (4.16% decrease) in the placebo group. However, there were no significant differences in body weight or body composition between placebo- and spatone-treated groups. Endurance capacity improved significantly in terms of VO2max and lactate accumulation after spatone supplement. The interleukin (IL)-10, tumor necrosis factor (TNF)-alpha, and IL-6 concentrations were not altered with spatone treatment or placebo in the rapid weight-loss condition; however, a positive relationship (R = 0.643, P = .023) was observed between the change in IL-6 and VO2max. Thus, our results are consistent with prior studies in that spatone supplementation could protect against iron loss induced by intense training, considering that spatone affects the modulation of inflammatory cytokines and exercise capacity. These preliminary results serve to facilitate the planning for the nutritional application of spatone with their exercise program for wrestlers.

Effect of Whole Body Horizontal Vibration Exercise in Chronic Low Back Pain Patients: Vertical Versus Horizontal Vibration Exercise.

OBJECTIVE: To elucidate the effect of a 12-week horizontal vibration exercise (HVE) in chronic low back pain (CLBP) patients as compared to vertical vibration exercise (VVE). METHODS: Twenty-eight CLBP patients were randomly assigned to either the HVE or VVE group. All participants performed the exercise for 30 minutes each day, three times a week, for a total of 12 weeks. Altered pain and functional ability were evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI), respectively. Changes in lumbar muscle strength, transverse abdominis (TrA) and multifidus muscle thicknesses, and standing balance were measured using an isokinetic dynamometer, ultrasonography, and balance parameters, respectively. These assessments were evaluated prior to treatment, 6 weeks and 12 weeks after the first treatment, and 4 weeks after the end of treatment (that is, 16 weeks after the first treatment). RESULTS: According to the repeated-measures analysis of variance, there were significant improvements with time on VAS, ODI, standing balance score, lumbar flexor, and extensor muscle strength (all p<0.001 in both groups) without any significant changes in TrA (p=0.153 in HVE, p=0.561 in VVE group) or multifidus (p=0.737 in HVE, p=0.380 in VVE group) muscle thickness. Further, there were no significant differences between groups according to time in any of the assessments. No adverse events were noticed during treatment in either group. CONCLUSION: HVE is as effective as VVE in reducing pain, strengthening the lumbar muscle, and improving the balance and functional abilities of CLBP patients. Vibrational exercise increases muscle strength without inducing muscle hypertrophy.

Resistance training increases fibroblast growth factor-21 and irisin levels in the skeletal muscle of Zucker diabetic fatty rats.

PURPOSE: Although the fibroblast growth factor-21 (FGF-21) and irisin roles are well demonstrated in metabolic disease, there have been no reports investigating the effect of resistance exercise on FGF-21 and irisin levels in diabetic skeletal muscles. Therefore, this study aimed to investigate the change of FGF-21 and irisin levels in various skeletal muscles, and their association with muscle strength, following 8 weeks of resistance training using Zucker diabetic fatty rats (type 2 diabetic animal models). METHODS: Twenty-four male lean (Zucker lean control, ZLC) and diabetic (Zucker diabetic fatty, ZDF) rats (age, 8 weeks old) were separated into 3 groups, lean control (ZLC-Con, n=8), diabetic control (ZDF-Con, n=8), and diabetic exercise-trained groups (ZDF-Ex, n=8). The rats in ZDF-Ex were trained to climb a 1-m vertical (85 degrees inclined) ladder with weights. Resistance training was performed with 10 repetitions/day for 12 weeks (3 days/week). The skeletal muscle levels of FGF-21 and irisin were measured using enzyme-linked immunosorbent assays. RESULTS: The levels of FGF-21 in the soleus (SOL) and extensor digitorum longus muscles of ZDF-Ex were higher (p<0.05) compared to levels in ZDF-Con. Additionally, we found a significantly higher irisin level in the SOL muscles of ZDF-Ex compared to that in ZDF-Con. Moreover, we found that the levels of FGF-21 (R=0.532, p=0.02) and irisin (R=0.498, p=0.03) had significant correlations with grip strength. CONCLUSION: Based on these results, resistance training may be an efficient intervention for increasing FGF-21 and irisin levels in type 2 diabetic (T2DM) skeletal muscles.

Direct observation of mode-specific phonon-band gap coupling in methylammonium lead halide perovskites.

Methylammonium lead iodide perovskite is an outstanding semiconductor for photovoltaics. One of its intriguing peculiarities is that the band gap of this perovskite increases with increasing lattice temperature. Despite the presence of various thermally accessible phonon modes in this soft material, the understanding of how precisely these phonons affect macroscopic material properties and lead to the peculiar temperature dependence of the band gap has remained elusive. Here, we report a strong coupling of a single phonon mode at the frequency of ~ 1 THz to the optical band gap by monitoring the transient band edge absorption after ultrafast resonant THz phonon excitation. Excitation of the 1 THz phonon causes a blue shift of the band gap over the temperature range of 185 ~ 300 K. Our results uncover the mode-specific coupling between one phonon and the optical properties, which contributes to the temperature dependence of the gap in the tetragonal phase.Methylammonium lead iodide perovskite, a promising material for efficient photovoltaics, shows a unique temperature dependence of its optical properties. Kim et al. quantify the coupling between the optical gap and a lattice phonon at 1 THz, which favorably contributes to the thermal variation of the gap.

Complexity in Acid-Base Titrations: Multimer Formation Between Phosphoric Acids and Imines.

Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid-base aggregates challenging. Here, we track such acid-base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid-base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid-base association constant is only around six times larger than that for the acid binding to an acid-base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis.

Bio-orthogonal conjugation and enzymatically triggered release of proteins within multi-layered hydrogels.

Hydrogels are facile architectures for the controlled presentation of proteins with far-reaching applications, from fundamental biological studies in three-dimensional culture to new regenerative medicine and therapeutic delivery strategies. Here, we demonstrate a versatile approach for spatially-defined presentation of engineered proteins within hydrogels through i) immobilization using bio-orthogonal strain-promoted alkyne-azide click chemistry and ii) dynamic protease-driven protein release using exogenously applied enzyme. Model fluorescent proteins were expressed using nonsense codon replacement to incorporate azide-containing unnatural amino acids in a site-specific manner toward maintaining protein activity: here, cyan fluorescent protein (AzCFP), mCherry fluorescent protein (AzmCh), and mCh decorated with a thrombin cut-site. (AzTMBmCh). Eight-arm poly(ethylene glycol) (PEG) was modified with dibenzylcyclooctyne (DBCO) groups and reacted with azide functionalized PEG in aqueous solution for rapid formation of hydrogels. Azide functionalized full-length fluorescent proteins were successfully incorporated into the hydrogel network by reaction with PEG-DBCO prior to gel formation. Temporal release and removal of select proteins (AzTMBmCh) was triggered with the application of thrombin and monitored in real-time with confocal microscopy, providing a responsive handle for controlling matrix properties. Hydrogels with regions of different protein compositions were created using a layering technique with thicknesses of hundreds of micrometers, affording opportunities for the creation of complex geometries on size scales relevant for controlling cellular microenvironments. STATEMENT OF SIGNIFICANCE: Controlling protein presentation within biomaterials is important for modulating interactions with biological systems. For example, native tissues are composed of subunits with different matrix compositions (proteins, stiffness) that dynamically interact with cells, influencing function and fate. Toward mimicking such temporally-regulated and spatially-defined microenvironments, we utilize bio-orthogonal click chemistry and protein engineering to create hydrogels with distinct regions of proteins and modify them over time. Through nonsense codon replacement, we site-specifically functionalize large proteins with i) azides for covalent conjugation and ii) an enzymatic cleavage site for user-defined release from hydrogels. Our results exemplify not only the ability to create unique bio-functionalized hydrogels with controlled mechanical properties, but also the potential for creating interesting interfaces for cell culture and tissue engineering applications.