Noncovalent Conjugation of OVA323 to ELP Micelles Increases Immune Response.

Subunit vaccines would benefit from a safe particle-based adjuvant. Elastin-like polypeptide (ELP)-based micelles are interesting candidate adjuvants due to their well-defined size and easy modification with protein-based cargo. Coiled coils can facilitate noncovalent modifications, while potentially enhancing antigen delivery through interaction with cell membranes. ELP micelles comprise ELP diblock copolymers that self-assemble above a critical micelle temperature. In this study, an amphiphilic ELP was conjugated to peptide "K", which forms a heterodimeric coiled-coil complex with peptide "E". Self-assembled "covalent" micelles containing ELP-OVA323 (i.e., model antigen OVA323 conjugated to ELP), "coiled-coil" micelles containing ELP-K/E-OVA323 and "hybrid" micelles containing ELP-K and ELP-OVA323 were shown to be monodisperse and spherical. Dendritic cells (DCs) were exposed to all micelle compositions, and T-cell proliferation was investigated. The presence of ELP-K enhanced micelle uptake and subsequent DC maturation, resulting in enhanced CD4+ T-cell proliferation, which makes ELPs with coiled coil-associated antigens a promising vaccine platform.

Larger stem to bone diameter ratio predicts lower cemented endoprosthesis failure.

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.

Photoprocessing of cationic triazacoronene: dissociation characteristics of polycyclic aromatic nitrogen heterocycles in interstellar environments.

Polycyclic aromatic nitrogen heterocycles (PANHs) are present in various astronomical environments where they are subjected to intense radiation. Their photodissociation pathways give crucial insights into the cycle of matter in the universe, yet so far only the dissociation characteristics of few PANHs have been investigated. Moreover, most experiments use single photon techniques that only reveal the initial dissociation step, and are thus unsuited to replicate astronomical environments and timescales. In this work, we use the Instrument for the Photodynamics of PAHs (i-PoP) at the Laboratory for Astrophysics to simulate the interstellar photodissociation of a model PANH, cationic triazacoronene (TAC˙+, C21H9N3). Comparing the observed fragments to similar PAHs such as the isoelectronic coronene can give mechanistic insight into PAH dissociation. For coronene the major photodissociation products were found to be C9H+, C10+, and C11+. In contrast, fragmentation in TAC˙+ is initiated by up to three HCN losses often in combination with H- or H2 losses. In the lower mass region, the fragments show similarities to comparable PAHs like coronene, but for TAC˙+ the inclusion of nitrogen atoms into the ionic fragments in the form of e.g. (di)cyanopolyynes is also observed. These nitrogen-containing species may be important tracers of regions in interstellar space where interstellar PANHs are being photodissociated.

Macroscopic and Microscopic Wettability of Graphene.

Interactions between water and graphene can be probed on a macroscopic level through wettability by measuring the water contact angle and on a microscopic level through water desorption kinetic studies using surface science methods. The contact angle studies of graphene pinpointed the critical role of sample preparation and measurement conditions in assessing the wettability of graphene. So far, studies of water desorption from graphene under the conditions of ultrahigh vacuum provided superior control over the environment but disregarded the importance of sample preparation. Here, we systematically examined the effect of the morphology of the growth substrate and of the transfer process on the macroscopic and microscopic wettability of graphene. Remarkably, the macroscopic wetting transparency of graphene does not always translate into microscopic wetting transparency, particularly in the case of an atomically defined Cu(111) substrate. Additionally, subtle differences in the type of substrates significantly alter the interactions between graphene and the first monolayer of adsorbed water but have a negligible effect on the apparent macroscopic wettability. This work looks into the correlations between the wetting properties of graphene, both on the macroscopic and microscopic scales, and highlights the importance of sample preparation in understanding the surface chemistry of graphene.

Ultrasensitive Field-Effect Biosensors Enabled by the Unique Electronic Properties of Graphene.

This review provides a critical overview of current developments on nanoelectronic biochemical sensors based on graphene. Composed of a single layer of conjugated carbon atoms, graphene has outstanding high carrier mobility and low intrinsic electrical noise, but a chemically inert surface. Surface functionalization is therefore crucial to unravel graphene sensitivity and selectivity for the detection of targeted analytes. To achieve optimal performance of graphene transistors for biochemical sensing, the tuning of the graphene surface properties via surface functionalization and passivation is highlighted, as well as the tuning of its electrical operation by utilizing multifrequency ambipolar configuration and a high frequency measurement scheme to overcome the Debye screening to achieve low noise and highly sensitive detection. Potential applications and prospectives of ultrasensitive graphene electronic biochemical sensors ranging from environmental monitoring and food safety, healthcare and medical diagnosis, to life science research, are presented as well.

Encapsulation of Graphene in the Hydrophobic Core of a Lipid Bilayer.

Theoretical simulations have predicted that a lipid bilayer forms a stable superstructure when a sheet of graphene is inserted in its hydrophobic core. We experimentally produced for the first time a lipid-graphene-lipid assembly by combining the Langmuir-Blodgett and the Langmuir-Schaefer methods. Graphene is sandwiched and remains flat within the hydrophobic core of the lipid bilayer. Using infrared spectroscopy, ellipsometry, and neutron reflectometry, we characterized the superstructure at every fabrication step. The hybrid superstructure is mechanically stable and graphene does not disturb the natural lipid bilayer structure.

Narrative Medicine Rounds: Promoting Student Well-Being during the Third Year of Medical School.

OBJECTIVES: Narrative medicine allows physicians and other health providers to share stories and reflect on the practice of medicine. Through the process of reflection and shared storytelling, narrative medicine may promote strategies for well-being and the prevention of physician burnout. Designed to foster skills to promote physician wellness, the required narrative medicine rounds activity during the family medicine clerkship at the Herbert Wertheim College of Medicine at Florida International University includes a written assignment and a small group session, during which students share their stories with their peers. METHODS: During the 2018-2019 academic year, a postsession survey asked students to identify strategies learned in the session that could be applied to future patient care and personal well-being; a thematic analysis of students' responses was conducted using inductive coding. Likert-style questions asked whether students learned something about themselves in this session, believed that they would write in the future, and understood the value of discussing significant patient encounters with peers. RESULTS: Identified themes for strategies for patient care fell into two categories: approaches to improve the patient care experience and methods for reflecting on patient interactions. Themes for strategies for future well-being fell into three categories: strategies to promote mental health, changes to interpersonal interactions, and self-reflection. Most students "strongly agreed" or "agreed" that this session taught them something about themselves and showed them the value of discussing significant patient encounters with peers, and that they would be likely to write about patient cases in the future. CONCLUSIONS: There was significant overlap in the themes related to strategies for personal well-being and those for patient care. Students were able to identify multiple, specific strategies to promote their own future well-being. These findings suggest that even a brief narrative medicine session may have an impact on students' understanding of strategies to prevent burnout and improve future patient care.

Ligand Identity-Induced Generation of Enhanced Oxidative Hydrogen Atom Transfer Reactivity for a CuII2(O2•-) Complex Driven by Formation of a CuII2(-OOH) Compound with a Strong O-H Bond.

A superoxide-bridged dicopper(II) complex, [CuII2(XYLO)(O2•-)]2+ (1) (XYLO = binucleating m-xylyl derivative with a bridging phenolate ligand donor and two bis(2-{2-pyridyl}ethyl)amine arms), was generated from chemical oxidation of the peroxide-bridged dicopper(II) complex [CuII2(XYLO)(O22-)]+ (2), using ferrocenium (Fc+) derivatives, in 2-methyltetrahydrofuran (MeTHF) at -125 °C. Using Me10Fc+, a 1 ⇆ 2 equilibrium was established, allowing for calculation of the reduction potential of 1 as -0.525 ± 0.01 V vs Fc+/0. Addition of 1 equiv of strong acid to 2 afforded the hydroperoxide-bridged dicopper(II) species [CuII2(XYLO)(OOH)]2+ (3). An acid-base equilibrium between 3 and 2 was achieved through spectral titrations using a derivatized phosphazene base. The pKa of 3 was thus determined to be 24 ± 0.6 in MeTHF at -125 °C. Using a thermodynamic square scheme and the Bordwell relationship, the hydroperoxo complex (3) O-H bond dissociation free energy (BDFE) was calculated as 81.8 ± 1.5 (BDE = 86.8) kcal/mol. The observed oxidizing capability of [CuII2(XYLO)(O2•-)]2+ (1), as demonstrated in H atom abstraction reactions with certain phenolic ArO-H and hydrocarbon C-H substrates, provides direct support for this experimentally determined O-H BDFE. A kinetic study reveals a very fast reaction of TEMPO-H with 1 in MeTHF, with k (-100 °C) = 5.6 M-1 s-1. Density functional theory (DFT) calculations reveal how the structure of 1 may minimize stabilization of the superoxide moiety, resulting in its enhanced reactivity. The thermodynamic insights obtained herein highlight the importance of the interplay between ligand design and the generation and properties of copper (or other metal ion) bound O2-derived reduced species, such as pKa, reduction potential, and BDFE; these may be relevant to the capabilities (i.e., oxidizing power) of reactive oxygen intermediates in metalloenzyme chemical system mediated oxidative processes.

Dynamic Tunneling Junctions at the Atomic Intersection of Two Twisted Graphene Edges.

The investigation of the transport properties of single molecules by flowing tunneling currents across extremely narrow gaps is relevant for challenges as diverse as the development of molecular electronics and sequencing of DNA. The achievement of well-defined electrode architectures remains a technical challenge, especially due to the necessity of high precision fabrication processes and the chemical instability of most bulk metals. Here, we illustrate a continuously adjustable tunneling junction between the edges of two twisted graphene sheets. The unique property of the graphene electrodes is that the sheets are rigidly supported all the way to the atomic edge. By analyzing the tunneling current characteristics, we also demonstrate that the spacing across the gap junction can be controllably adjusted. Finally, we demonstrate the transition from the tunneling regime to contact and the formation of an atomic-sized junction between the two edges of graphene.

Ultrasensitive Ethene Detector Based on a Graphene-Copper(I) Hybrid Material.

Ethene is a highly diffusive and relatively unreactive gas that induces aging responses in plants in concentrations as low as parts per billion. Monitoring concentrations of ethene is critically important for transport and storage of food crops, necessitating the development of a new generation of ultrasensitive detectors. Here we show that by functionalizing graphene with copper complexes biologically relevant concentrations of ethene and of the spoilage marker ethanol can be detected. Importantly, in addition these sensors provide us with important insights into the interactions between molecules, a key concept in chemistry. Chemically induced dipole fluctuations in molecules as they undergo a chemical reaction are harvested in an elegant way through subtle field effects in graphene. By exploiting changes in the dipole moments of molecules that occur upon a chemical reaction we are able to track the reaction and provide mechanistic insight that was, until now, out of reach.

Single molecule detection with graphene and other two-dimensional materials: nanopores and beyond.

Graphene and other two dimensional (2D) materials are currently integrated into nanoscaled devices that may - one day - sequence genomes. The challenge to solve is conceptually straightforward: cut a sheet out of a 2D material and use the edge of the sheet to scan an unfolded biomolecule from head to tail. As the scan proceeds - and because 2D materials are atomically thin - the information provided by the edge might be used to identify different segments - ideally single nucleotides - in the biomolecular strand. So far, the most efficient approach was to drill a nano-sized pore in the sheet and use this pore as a channel to guide and detect individual molecules by measuring the electrochemical ionic current. Nanoscaled gaps between two electrodes in 2D materials recently emerged as powerful alternatives to nanopores. This article reviews the current status and prospects of integrating 2D materials in nanopores, nanogaps and similar devices for single molecule biosensing applications. We discuss the pros and cons, the challenges, and the latest achievements in the field. To achieve high-throughput sequencing with 2D materials, interdisciplinary research is essential.

Spatiotemporal Control of Doxorubicin Delivery from "Stealth-Like" Prodrug Micelles.

In the treatment of cancer, targeting of anticancer drugs to the tumor microenvironment is highly desirable. Not only does this imply accurate tumor targeting but also minimal drug release en route to the tumor and maximal drug release once there. Here we describe high-loading, "stealth-like" doxorubicin micelles as a pro-drug delivery system, which upon light activation, leads to burst-like doxorbicin release. Through this approach, we show precise spatiotemporal control of doxorubicin delivery to cells in vitro.

Chemistry at the Edge of Graphene.

The selective functionalization of graphene edges is driven by the chemical reactivity of its carbon atoms. The chemical reactivity of an edge, as an interruption of the honeycomb lattice of graphene, differs from the relative inertness of the basal plane. In fact, the unsaturation of the pz orbitals and the break of the π conjugation on an edge increase the energy of the electrons at the edge sites, leading to specific chemical reactivity and electronic properties. Given the relevance of the chemistry at the edges in many aspects of graphene, the present Review investigates the processes and mechanisms that drive the chemical functionalization of graphene at the edges. Emphasis is given to the selective chemical functionalization of graphene edges from theoretical and experimental perspectives, with a particular focus on the characterization tools available to investigate the chemistry of graphene at the edge.

Controlled, reversible, and nondestructive generation of uniaxial extreme strains (>10%) in graphene.

Theoretical calculations have predicted that extreme strains (>10%) in graphene would result in novel applications. However, up to now the highest reported strain reached ∼1.3%. Here, we demonstrate uniaxial strains >10% by pulling graphene using a tensile-MEMS. To prevent it from slipping away it was locally clamped with epoxy using a femtopipette. The results were analyzed using Raman spectroscopy and optical tracking. Furthermore, analysis proved the process to be reversible and nondestructive for the graphene.

Highly strained graphene samples of varying thickness and comparison of their behaviour.

Mechanically straining graphene opens the possibility to exploit new properties linked to the stressed lattice of this two-dimensional material. In particular, theoretical analyses have forecast that straining graphene by more than 10% is a requirement for many novel applications that have not yet been experimentally demonstrated. Recently, we reported having achieved 12.5% strain in a trilayer graphene sample (3LG) in a controlled, reversible and non-destructive way. In this paper, we explore our method by straining samples of varying thicknesses and comparing their behavior, where strains of 14% and 11% were achieved for monolayer and four-layer graphene (4LG), respectively. For the analysis, optical tracking and the correspondent Raman spectra were taken. While doing so, we observed slippage between two layers in a bilayer sample of which one layer was clamped on one side only. The obtained results when stretching different samples to extreme strains demonstrated the exceptional elasticity of graphene, which might be essential for practical applications. Hysteretic effects observed in the partially clamped layer hints at small energy losses during slippage. This may shed new light on the superlubricity property of graphene that has been reported in the literature.

Parts and wholes: the human microbiome, ecological ontology, and the challenges of community.

The early results of the Human Microbiome Project, released in June 2012, add to the overwhelming data that show that there are literally trillions of microbes that live in and on each human individual. This research raises profound questions about what it means to be an individual organism, human or otherwise. In this paper, we ask two broad questions: (1) how might we conceive of an individual organism, given these results? and (2) in light of this emerging conception of the individual organism, what are the implications for how humans conceive of their own self-sufficiency and interact with other members of the living world? We highlight the ontological and political presuppositions animating this research and return to Aristotle for insights into how to conceive of and how to behave towards and within a diverse community of interdependent living parts that function together as one.

Covalent Benzenesulfonic Functionalization of a Graphene Nanopore for Enhanced and Selective Proton Transport.

A fundamental understanding of proton transport through graphene nanopores, defects, and vacancies is essential for advancing two-dimensional proton exchange membranes (PEMs). This study employs ReaxFF molecular dynamics, metadynamics, and density functional theory to investigate the enhanced proton transport through a graphene nanopore. Covalently functionalizing the nanopore with a benzenesulfonic group yields consistent improvements in proton permeability, with a lower activation barrier (≈0.15 eV) and increased proton selectivity over sodium cations. The benzenesulfonic functionality acts as a dynamic proton shuttle, establishing a favorable hydrogen-bonding network and an efficient proton transport channel. The model reveals an optimal balance between proton permeability and selectivity, which is essential for effective proton exchange membranes. Notably, the benzenesulfonic-functionalized graphene nanopore system achieves a theoretically estimated proton diffusion coefficient comparable to or higher than the current state-of-the-art PEM, Nafion. Ergo, the benzenesulfonic functionalization of graphene nanopores, firmly holds promise for future graphene-based membrane development in energy conversion devices.

Proton-selective coating enables fast-kinetics high-mass-loading cathodes for sustainable zinc batteries.

The pressing demand for sustainable energy storage solutions has spurred the burgeoning development of aqueous zinc batteries. However, kinetics-sluggish Zn2+ as the dominant charge carriers in cathodes leads to suboptimal charge-storage capacity and durability of aqueous zinc batteries. Here, we discover that an ultrathin two-dimensional polyimine membrane, featured by dual ion-transport nanochannels and rich proton-conduction groups, facilitates rapid and selective proton passing. Subsequently, a distinctive electrochemistry transition shifting from sluggish Zn2+-dominated to fast-kinetics H+-dominated Faradic reactions is achieved for high-mass-loading cathodes by using the polyimine membrane as an interfacial coating. Notably, the NaV3O8·1.5H2O cathode (10 mg cm-2) with this interfacial coating exhibits an ultrahigh areal capacity of 4.5 mAh cm-2 and a state-of-the-art energy density of 33.8 Wh m-2, along with apparently enhanced cycling stability. Additionally, we showcase the applicability of the interfacial proton-selective coating to different cathodes and aqueous electrolytes, validating its universality for developing reliable aqueous batteries.

Tunable visible light emission of self-assembled rhomboidal metallacycles.

Supramolecular coordination complexes (SCCs) have been proposed for applications necessitating photon emitting properties; however, two critical characteristics, facile tunability and high emission quantum yields, have yet to be demonstrated on SCC platforms. Herein, a series of functionalized D2h [D2A2] rhomboids (D = 2,6-bis(4-ethynylpyridine)aniline-based ligands; A = 2,9-bis[trans-Pt(PEt3)2NO3]phenanthrene) is described with emission wavelengths spanning the visible region (λmax = 476-581 nm). Tuning was achieved by simple functional group modifications para to the aniline amine on the donor building block. Steady-state absorption and emission profiles were obtained for each system and are discussed. When the Hammett σ(para) constants for the functional groups para to the aniline amine were plotted versus the wavenumber (cm(-1)) for the λmax of the emission profile, a linear relationship was observed. By utilizing this relationship, the emission wavelength of a given rhomboid can be predetermined on the basis of the Hammett constant of the functionality employed on the donor precursor. This range of visible light emission for a suite of simple rhomboids along with the predictive nature of the wavelength of emission is unprecedented for these types of systems.