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Crystals are known to grow nonclassically or via four classical modes (the layer-by-layer, dislocation-driven, dendritic, and normal modes, which generally involve minimal interfacet surface diffusion). The field of nanoscience considers this framework to interpret how nanocrystals grow; yet, the growth of many anisotropic nanocrystals remains enigmatic, suggesting that the framework may be incomplete. Here, we study the solution-phase growth of pentatwinned Au nanorods without Br, Ag, or surfactants. Lower supersaturation conditions favored anisotropic growth, which appeared at variance with the known modes. Temporal electron microscopy revealed kinetically limited adatom funneling, as adatoms diffused asymmetrically along the vicinal facets (situated inbetween the {100} side-facets and {111} end-facets) of our nanorods. These vicinal facets were perpetuated throughout the synthesis and, especially at lower supersaturation, facilitated {100}-to-vicinal-to-{111} adatom diffusion. We derived a growth model from classical theory in view of our findings, which showed that our experimental growth kinetics were consistent with nanorods growing via two modes simultaneously: radial growth occurred via the layer-by-layer mode on {100} side-facets, whereas the asymmetric interfacet diffusion of adatoms to {111} end-facets mediated longitudinal growth. Thus, shape anisotropy was not driven by modulating the relative rates of monomer deposition on different facets, as conventionally thought, but rather by modulating the relative rates of monomer integration via interfacet diffusion. This work shows how controlling supersaturation, a thermodynamic parameter, can uncover distinct kinetic phenomena on nanocrystals, such as asymmetric interfacet surface diffusion and a fundamental growth mode for which monomer deposition and integration occur on different facets.

Recent advances in biomaterials integrate metal nanoparticles with hydrogels to generate composite materials that exhibit new or improved properties. By precisely controlling the composition, arrangement and interactions of their constituents, these hybrid materials facilitate biomedical applications through myriad approaches. In this work we seek to highlight three popular frameworks for designing metal nanoparticle-hydrogel hybrid materials for biomedical applications. In the first approach, the properties of metal nanoparticles are incorporated into a hydrogel matrix such that the composite is selectively responsive to stimuli such as light and magnetic flux, enabling precisely activated therapeutics and self-healing biomaterials. The second approach mediates the dynamic reorganization of metal nanoparticles based on environment-directed changes in hydrogel structure, leading to chemosensing, microbial and viral detection, and drug-delivery capabilities. In the third approach, the hydrogel matrix spatially arranges metal nanoparticles to produce metamaterials or passively enhance nanoparticle properties to generate improved substrates for biomedical applications including tissue engineering and wound healing. This article reviews the construction, properties and biomedical applications of metal nanoparticle-hydrogel composites, with a focus on how they help to prevent, diagnose and treat diseases. Discussion includes how the composites lead to new or improved properties, how current biomedical research leverages these properties and the emerging directions in this growing field.

Mucus is a complex viscoelastic gel and acts as a barrier covering much of the soft tissue in the human body. High vascularization and accessibility have motivated drug delivery to various mucosal surfaces; however, these benefits are hindered by the mucus layer. To overcome the mucus barrier, many nanomedicines have been developed, with the goal of improving the efficacy and bioavailability of drug payloads. Two major nanoparticle-based strategies have emerged to facilitate mucosal drug delivery, namely, mucoadhesion and mucopenetration. Generally, mucoadhesive nanoparticles promote interactions with mucus for immobilization and sustained drug release, whereas mucopenetrating nanoparticles diffuse through the mucus and enhance drug uptake. The choice of strategy depends on many factors pertaining to the structural and compositional characteristics of the target mucus and mucosa. While there have been promising results in preclinical studies, mucus-nanoparticle interactions remain poorly understood, thus limiting effective clinical translation. This article reviews nanomedicines designed with mucoadhesive or mucopenetrating properties for mucosal delivery, explores the influence of site-dependent physiological variation among mucosal surfaces on efficacy, transport, and bioavailability, and discusses the techniques and models used to investigate mucus-nanoparticle interactions. The effects of non-homeostatic perturbations on protein corona formation, mucus composition, and nanoparticle performance are discussed in the context of mucosal delivery. The complexity of the mucosal barrier necessitates consideration of the interplay between nanoparticle design, tissue-specific differences in mucus structure and composition, and homeostatic or disease-related changes to the mucus barrier to develop effective nanomedicines for mucosal delivery.

BACKGROUND: Unprecedented demand for N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic has led to a global shortage of these masks. We validated a rapidly applicable, low-cost decontamination protocol in compliance with regulatory standards to enable the safe reuse of N95 respirators. METHODS: We inoculated 4 common models of N95 respirators with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and evaluated viral inactivation after disinfection for 60 minutes at 70°C and 0% relative humidity. Similarly, we evaluated thermal disinfection at 0% to 70% relative humidity for masks inoculated with Escherichia coli. We assessed masks subjected to multiple cycles of thermal disinfection for structural integrity using scanning electron microscopy and for protective functions using standards of the United States National Institute for Occupational Safety and Health for particle filtration efficiency, breathing resistance and respirator fit. RESULTS: A single heat treatment rendered SARS-CoV-2 undetectable in all mask samples. Compared with untreated inoculated control masks, E. coli cultures at 24 hours were virtually undetectable from masks treated at 70°C and 50% relative humidity (optical density at 600 nm wavelength, 0.02 ± 0.02 v. 2.77 ± 0.09, p < 0.001), but contamination persisted for masks treated at lower relative humidity. After 10 disinfection cycles, masks maintained fibre diameters similar to untreated masks and continued to meet standards for fit, filtration efficiency and breathing resistance. INTERPRETATION: Thermal disinfection successfully decontaminated N95 respirators without impairing structural integrity or function. This process could be used in hospitals and long-term care facilities with commonly available equipment to mitigate the depletion of N95 masks.

Behaviour plays a crucial role in a species’ ability to cope with environmental challenges. However, this ability may be affected by repeatable individual differences in behaviour, a pattern described as animal personality. The consideration of animal personality is therefore essential when understanding how a species copes with its environmental stressors. For sand bubbler crabs, feeding is often disrupted by environmental interference, in the forms of predatory events and human recreational activities. How these crabs deal with such disruption is, however, not well documented. Here, we characterised the foraging and risk-taking behaviours of Dotilla wichmanni when responding to induced disruption. Whether these are personality traits and if they form part of a behavioural syndrome were also examined. We quantify both behaviours by taking four measures (two per behaviour). All behavioural measures were consistently different among individuals, suggesting that D. wichmanni exhibits personality. Results further suggest that they could cope with some environmental interference, although this is limited. Crabs did not vary the time spent hiding in burrows with each repeated disruption nor did behavioural plasticity differ between individuals. Notwithstanding these, the absence of support for a foraging–risk propensity behavioural syndrome points to possible complexity in the crabs' coping ability.

Background: Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a long-standing question in infectious disease epidemiology. Methods: Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols. Results: The analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1 and 5 days post-symptom onset. Conclusions: Intrinsic case variation in rVL facilitates overdispersion in the transmissibility of emerging respiratory viruses. Our findings present considerations for disease control in the COVID-19 pandemic as well as future outbreaks of novel viruses. Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program, NSERC Senior Industrial Research Chair program and the Toronto COVID-19 Action Fund., eLife digest To understand how viruses spread scientists look at two things. One is – on average – how many other people each infected person spreads the virus to. The other is how much variability there is in the number of people each person with the virus infects. Some viruses like the 2009 influenza H1N1, a new strain of influenza that caused a pandemic beginning in 2009, spread pretty uniformly, with many people with the virus infecting around two other people. Other viruses like SARS-CoV-2, the one that causes COVID-19, are more variable. About 10 to 20% of people with COVID-19 cause 80% of subsequent infections – which may lead to so-called superspreading events – while 60-75% of people with COVID-19 infect no one else. Learning more about these differences can help public health officials create better ways to curb the spread of the virus. Chen et al. show that differences in the concentration of virus particles in the respiratory tract may help to explain why superspreaders play such a big role in transmitting SARS-CoV-2, but not the 2009 influenza H1N1 virus. Chen et al. reviewed and extracted data from studies that have collected how much virus is present in people infected with either SARS-CoV-2, a similar virus called SARS-CoV-1 that caused the SARS outbreak in 2003, or with 2009 influenza H1N1. Chen et al. found that as the variability in the concentration of the virus in the airways increased, so did the variability in the number of people each person with the virus infects. Chen et al. further used mathematical models to estimate how many virus particles individuals with each infection would expel via droplets or aerosols, based on the differences in virus concentrations from their analyses. The models showed that most people with COVID-19 infect no one because they expel little – if any – infectious SARS-CoV-2 when they talk, breathe, sing or cough. Highly infectious individuals on the other hand have high concentrations of the virus in their airways, particularly the first few days after developing symptoms, and can expel tens to thousands of infectious virus particles per minute. By contrast, a greater proportion of people with 2009 influenza H1N1 were potentially infectious but tended to expel relatively little infectious virus when the talk, sing, breathe or cough. These results help explain why superspreaders play such a key role in the ongoing pandemic. This information suggests that to stop this virus from spreading it is important to limit crowd sizes, shorten the duration of visits or gatherings, maintain social distancing, talk in low volumes around others, wear masks, and hold gatherings in well-ventilated settings. In addition, contact tracing can prioritize the contacts of people with high concentrations of virus in their airways.

CONTEXTE: La demande sans précédent de respirateurs N95 durant la pandémie de maladie à coronavirus 2019 (COVID-19) a entraîné une pénurie mondiale. Nous avons validé un protocole de décontamination rapide et économique répondant aux normes réglementaires afin de permettre la réutilisation sûre de ce type de masque. MÉTHODES: Nous avons contaminé 4 modèles courants de respirateurs N95 avec le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) et avons évalué l’inactivation virale après une désinfection de 60 minutes à 70 °C et à une humidité relative de 0 %. De même, nous avons étudié l’efficacité de la désinfection thermique, à une humidité relative allant de 0 % à 70 %, de masques contaminés à Escherichia coli. Enfin, nous avons examiné des masques soumis à de multiples cycles de désinfection thermique: nous avons évalué leur intégrité structurelle à l’aide d’un microscope à balayage, et leurs propriétés protectrices au moyen des normes du National Institute for Occupational Safety and Health des États-Unis relatives à la filtration particulaire, à la résistance respiratoire et à l’ajustement. RÉSULTATS: Une seule désinfection thermique a suffi pour que le SRAS-CoV-2 ne soit plus décelable sur les masques étudiés. En ce qui concerne les masques contaminés à E. coli, une culture de 24 heures a révélé que la bactérie n’était pratiquement plus décelable sur les masques désinfectés à 70 °C et à une humidité relative de 50 %, contrairement aux masques non désinfectés (densité optique à une longueur d’onde de 600 nm : 0,02 ± 0,02 contre 2,77 ± 0,09; p < 0,001), mais qu’elle persistait sur les masques traités à une humidité relative moindre. Les masques ayant subi 10 cycles de désinfection avaient toujours des fibres de diamètre semblable à celui des fibres des masques non traités, et ils répondaient encore aux normes d’ajustement, de filtration et de résistance respiratoire. INTERPRÉTATION: La désinfection thermique a réussi à décontaminer les respirateurs N95 sans compromettre leur intégrité structurelle ni modifier leurs propriétés. Elle pourrait se faire dans les hôpitaux et les établissements de soins de longue durée avec de l’équipement facilement accessible, ce qui réduirait la pénurie de N95.

Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a longstanding question in infectious disease epidemiology. Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols. Our analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1-5 days post-symptom onset. Our findings show how individual case variations influence virus transmissibility and present considerations for disease control in the COVID-19 pandemic.Significance StatementFor some emerging infectious diseases, including COVID-19, few cases cause most secondary infections. Others, like influenza A(H1N1)pdm09, spread more homogenously. The virological factors that mediate such distinctions in transmissibility remain unelucidated, prohibiting the development of specific disease control measures. We find that intrinsic case variation in respiratory viral load (rVL) facilitates overdispersion, and superspreading, for COVID-19 but more homogeneous transmission for A(H1N1)pdm09. We interpret the influence of heterogeneity in rVL on individual infectiousness by modelling likelihoods of shedding viable virus via respiratory droplets and aerosols. We analyze the distribution and kinetics of SARS-CoV-2 rVL, including across age and symptomatology subgroups. Our findings compare individual infectiousness across COVID-19 and A(H1N1)pdm09 cases and present quantitative guidance on triaging COVID-19 contact tracing.

BackgroundThe unprecedented demand and consequent global shortage of N95 respirators during the COVID-19 pandemic have left frontline workers vulnerable to infection. To potentially expand the supply, we validated a rapidly applicable low-cost decontamination protocol in compliance with regulatory standards to enable the safe reuse of personalized, disposable N95-respirators.MethodsFour common models of N95-respirators were disinfected for 60 minutes at 70°C either at 0% or 50% relative humidity (RH). Effective inactivation of SARS-CoV-2 and E. coli was evaluated in inoculated masks. The N95 filter integrity was examined with scanning electron microscopy. The protective function of disinfected N95 respirators was tested against US NIOSH standards for particle filtration efficiency, breathing resistance and respirator fit.ResultsA single heat treatment inactivated both SARS-CoV-2 (undetectable, detection limit: 100 TCID50/ml) and E. coli (0 colonies at 50%RH) in all four respirator models. Even N95-respirators that underwent ten decontamination cycles maintained their integrity and met US-governmental criteria for approval regarding fit, filtration efficiency and breathing resistance. Scanning electron microscopy demonstrated maintained N95 fiber diameter compared to baseline.InterpretationThermal disinfection enables large-scale, low cost decontamination of existing N95 respirators using commonly sourced equipment during the COVID-19 pandemic. This process could be used in hospitals and long term care facilities and also provides a feasible approach to expand the N95 supply in low- and middle-income regions.

During the Covid-19 pandemic, pristine and reprocessed N95 respirators are crucial equipment towards limiting nosocomial infections. The NIOSH test certifying the N95 rating, however, poorly simulates aerosols in healthcare settings, limiting our understanding of the exposure risk for healthcare workers wearing these masks, especially reprocessed ones. We used experimental conditions that simulated the sizes, densities and airflow properties of infectious aerosols in healthcare settings. We analyzed the penetration and leakage of aerosols through pristine and reprocessed N95 respirators. Seven reprocessing methods were investigated. Our findings suggest that pristine and properly reprocessed N95 respirators effectively limit exposure to infectious aerosols, but that care must be taken to avoid the elucidated degradation mechanisms and limit noncompliant wear.

Summary Recent methodological advances have led to unprecedented precision in the immobilization of metal nanoparticles. These methodologies come from a broad range of disciplines and organize nanoparticle building blocks into a diverse selection of distinct architectures—from small arrays to ordered superstructures. Because properties can be dictated by assembly, architectures can present enhanced properties of the constituent nanoparticles or generate emergent properties of the collective architecture that are unavailable to their constituent nanoparticles. Functional architectures use these properties to further tailor and optimize performance in myriad applications. This review discusses the methodological advances that enable the immobilization of metal nanoparticles in distinct two- and three-dimensional architectures. Discussion will include their distinctions, properties associated with the assemblies and their applications, and the key challenges and future directions in this growing field.

Nanoparticles are heavily researched for environmental applications, such as photocatalytic water treatment, however practical separation of nanoparticles from colloidal dispersions remains a critical challenge. Here, we demonstrate a new approach to nanoparticle recovery, combining the advantages of flocculation with magnetic separation to enable simple collection of non-magnetic nanoparticles. Flocculant polymers were coated onto magnetic nanoparticles (Fe3O4@SiO2) to prepare reusable magnetic flocculants (MFs). When added to colloidal nanoparticle dispersions, MFs aggregate with the suspended nanoparticles to form magnetically responsive flocs, which upon separation can be reversibly deflocculated for nanoparticle release, and reused in a closed loop process. High separation efficiency was attained in a variety of nanoparticle suspensions, including Au, Ag, Pd, Pt, and TiO2, stabilized by different coatings and surface charge. The MFs were shown to be recyclable for photocatalytic treatment of naphthenic acids in oil sands process-affected water (OSPW) and selenate in flue gas desulfurization wastewater (FGDW). Magnetic flocculation thus represents a general platform and alternative paradigm for nanoparticle separation, with potential applications in water treatment and remediation of nanoparticle pollution. Furthermore, given that flocculant chemicals can be recovered and reused in this process, magnetic flocculation may also serve as an environmentally sustainable solution to conventional flocculation challenges.

Signalling behaviour is integral to animal contests. However, post-contest signals, such as victory displays, have received relatively little attention. One hypothesised function of victory displays is to ensure a more lasting dominance by reducing the risk of losers re-initiating a new contest with winners. Despite several theoretical studies using game theory that support this hypothesis, empirical support for the understanding of when and why victory displays are used with respect to browbeating is lacking. We use a common South-East Asian mangrove crab, Perisesarma eumolpe, to examine whether the performance of victory displays by winners, among other factors, affects the time of fight re-initiation by losers, if at all re-initiated. Using mixed-effects survival analysis models, we analysed 77 fights from 27 staged contest trials between randomly paired males. We found losers that experienced victory display performed by winners, presented a decreased instantaneous hazard rate of re-initiating a new fight than losers that did not. These results corroborate previous game theoretical models indicating that victory displays may function to reduce the chances of losers re-initiating another fight. In discouraging losers from restarting a fight, winners reduce the potential costs of a future contest.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Human umbilical cord mesenchymal stromal cells possess considerable therapeutic promise for acute respiratory distress syndrome. Umbilical cord mesenchymal stromal cells may exert therapeutic effects via extracellular vesicles, while priming umbilical cord mesenchymal stromal cells may further enhance their effect. The authors investigated whether interferon-γ–primed umbilical cord mesenchymal stromal cells would generate mesenchymal stromal cell–derived extracellular vesicles with enhanced effects in Escherichia coli (E. coli) pneumonia. Methods In a university laboratory, anesthetized adult male Sprague–Dawley rats (n = 8 to 18 per group) underwent intrapulmonary E. coli instillation (5 × 109 colony forming units per kilogram), and were randomized to receive (a) primed mesenchymal stromal cell–derived extracellular vesicles, (b) naïve mesenchymal stromal cell–derived extracellular vesicles (both 100 million mesenchymal stromal cell–derived extracellular vesicles per kilogram), or (c) vehicle. Injury severity and bacterial load were assessed at 48 h. In vitro studies assessed the potential for primed and naïve mesenchymal stromal cell–derived extracellular vesicles to enhance macrophage bacterial phagocytosis and killing. Results Survival increased with primed (10 of 11 [91%]) and naïve (8 of 8 [100%]) mesenchymal stromal cell–derived extracellular vesicles compared with vehicle (12 of 18 [66.7%], P = 0.038). Primed—but not naïve—mesenchymal stromal cell–derived extracellular vesicles reduced alveolar–arterial oxygen gradient (422 ± 104, 536 ± 58, 523 ± 68 mm Hg, respectively; P = 0.008), reduced alveolar protein leak (0.7 ± 0.3, 1.4 ± 0.4, 1.5 ± 0.7 mg/ml, respectively; P = 0.003), increased lung mononuclear phagocytes (23.2 ± 6.3, 21.7 ± 5, 16.7 ± 5 respectively; P = 0.025), and reduced alveolar tumor necrosis factor alpha concentrations (29 ± 14.5, 35 ± 12.3, 47.2 ± 6.3 pg/ml, respectively; P = 0.026) compared with vehicle. Primed—but not naïve—mesenchymal stromal cell–derived extracellular vesicles enhanced endothelial nitric oxide synthase production in the injured lung (endothelial nitric oxide synthase/β-actin = 0.77 ± 0.34, 0.25 ± 0.29, 0.21 ± 0.33, respectively; P = 0.005). Both primed and naïve mesenchymal stromal cell–derived extracellular vesicles enhanced E. coli phagocytosis and bacterial killing in human acute monocytic leukemia cell line (THP-1) in vitro (36.9 ± 4, 13.3 ± 8, 0.1 ± 0.01%, respectively; P = 0.0004) compared with vehicle. Conclusions Extracellular vesicles from interferon-γ–primed human umbilical cord mesenchymal stromal cells more effectively attenuated E. coli–induced lung injury compared with extracellular vesicles from naïve mesenchymal stromal cells, potentially via enhanced macrophage phagocytosis and killing of E. coli.

The response to the COVID-19 epidemic is generating severe shortages of personal protective equipment around the world. In particular, the supply of N95 respirator masks has become severely depleted, with supplies having to be rationed and health care workers having to use masks for prolonged periods in many countries. We sought to test the ability of 7 different decontamination methods: autoclave treatment, ethylene oxide gassing (ETO), low temperature hydrogen peroxide gas plasma (LT-HPGP) treatment, vaporous hydrogen peroxide (VHP) exposure, peracetic acid dry fogging (PAF), ultraviolet C irradiation (UVCI) and moist heat (MH) treatment to decontaminate a variety of different N95 masks following experimental contamination with SARS-CoV-2 or vesicular stomatitis virus as a surrogate. In addition, we sought to determine whether masks would tolerate repeated cycles of decontamination while maintaining structural and functional integrity. All methods except for UVCI were effective in total elimination of viable virus from treated masks. We found that all respirator masks tolerated at least one cycle of all treatment modalities without structural or functional deterioration as assessed by fit testing; filtration efficiency testing results were mostly similar except that a single cycle of LT-HPGP was associated with failures in 3 of 6 masks assessed. VHP, PAF, UVCI, and MH were associated with preserved mask integrity to a minimum of 10 cycles by both fit and filtration testing. A similar result was shown with ethylene oxide gassing to the maximum 3 cycles tested. Pleated, layered non-woven fabric N95 masks retained integrity in fit testing for at least 10 cycles of autoclaving but the molded N95 masks failed after 1 cycle; filtration testing however was intact to 5 cycles for all masks. The successful application of autoclaving for layered, pleated masks may be of particular use to institutions globally due to the virtually universal accessibility of autoclaves in health care settings. Given the ability to modify widely available heating cabinets on hospital wards in well-resourced settings, the application of moist heat may allow local processing of N95 masks.

Rapid and portable diagnosis of pathogenic bacteria can save lives lost from infectious diseases. Biosensors based on a "chemical nose" approach are attracting interest because they are versatile but the governing interactions between bacteria and the biosensors are poorly understood. Here, we use a "chemical nose" biosensor based on gold nanoparticles to explore the role of extracellular polymeric substances in bacteria-nanoparticle interactions. We employ simulations using Maxwell-Garnett theory to show how the type and extent of aggregation of nanoparticles influence their colorimetric response to bacteria. Using eight different species of Gram-positive and Gram-negative bacteria, we demonstrate that this "chemical nose" can detect and identify bacteria over two orders of magnitude of concentration (89% accuracy). Additionally, the "chemical nose" differentiates between binary and tertiary mixtures of the three most common hospital-isolated pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (100% accuracy). We demonstrate that the complex interactions between nanoparticles and bacterial surface determine the colorimetric response of gold nanoparticles and thus, govern the performance of "chemical nose" biosensors.

A growing understanding of the fundamental role of proteins in diseases has advanced the development of quantitative protein assays in the medical field. Current techniques for protein analysis include enzyme-linked immunosorbent assays (ELISA), flow cytometry, mass spectrometry, and immunohistochemistry. However, many of these conventional strategies require specialized training, expensive antibodies, or sophisticated equipment, raising assay costs and limiting their application to laboratory analysis. Here, we present the application of a "chemical nose" type colorimetric gold nanoparticle sensor for detection, quantification, and identification of single proteins, protein mixtures, and proteins within the complex environment of human serum. The unique interactions between a mixture of two different gold nanoparticle morphologies (spherical and branched) and six separate proteins (bovine serum albumin, human serum albumin, immunoglobulin G, fibrinogen, lysozyme, and hemoglobin) generated distinguishable protein- and concentration-dependent absorption spectra, even at nanomolar concentrations. Furthermore, we show that this response is sensitive to the relative abundance of different proteins in solution, permitting analysis of protein mixtures. Finally, we demonstrate the ability to distinguish human serum samples with and without a clinically relevant two-fold increase in immunoglobulin G, without the use of expensive reagents or complicated sample processing.

Surface fouling remains an exigent issue for many biological implants. Unwanted solutes adsorb to reduce device efficiency and hasten degradation while increasing the risks of microbial colonization and adverse inflammatory response. To address unwanted fouling in modern implants in vivo, surface modification with antifouling polymers has become indispensable. Recently, zwitterionic self-assembled monolayers, which contain two or more charged functional groups but are electrostatically neutral and form highly hydrated surfaces, have been the focus of many antifouling coatings. Reports using various compositions of zwitterionic polymer brushes have demonstrated ultralow fouling in the ng/cm2 range. These coatings, however, are thick and can hinder the target application of biological devices. Here, we report an ultrathin (8.52 A) antifouling self-assembled monolayer composed of cysteine that is amenable to facile fabrication. The antifouling characteristics of the zwitterionic surfaces were evaluated against bovine serum albumin, fibrinogen, and human blood in real time using quartz crystal microbalance and surface plasmon resonance imaging. Compared to untreated gold surfaces, the ultrathin cysteine coating reduced the adsorption of bovine serum albumin by 95% (43 ng/cm2 adsorbed) after 3 h and 90% reduction after 24 h. Similarly, the cysteine self-assembled monolayer reduced the adsorption of fibrinogen as well as human blood by >90%. The surfaces were further characterized using scanning electron microscopy: protein-enhanced adsorption and cellular adsorption in human blood was found on untreated surfaces but not on the cysteine SAM-protected surfaces. These findings suggest that surfaces can be functionalized with an ultrathin layer of cysteine to resist the adsorption of key proteins, with performance comparable to zwitterionic polymer brushes. As such, cysteine surface coatings are a promising methodology to improve the long-term utility of biological devices.

The adhesion properties of Staphylococcus aureus on palladium–cobalt (Pd–Co) alloy nanostructures with various cross-sectional geometries have been characterised. They include solid core, hollow, c-shaped, and x-shaped pillars. These pillars have unique funnel-shaped geometric features on the top surfaces with average included angles between ∼142o and ∼149o. The success rates of cell attachment on these pillar tops were quantified by using field emission scanning electron microscopy techniques. Results show the Staphylococcus aureus attachment rates of Pd–Co solid core, hollow, and x-shaped pillars are statistically indistinguishable with success rate up to 82%. X-shaped pillars have the lowest attachment rate among the four geometries of 46 ± 5%.

A new methodology was developed to trap polystyrene or latex nanospheres in nanocrystalline nickel columnar nanostructures with various cross-sectional geometries. After filling the column interiors with polystyrene or latex nanospheres with diameters of ∼300 and 500 nm, respectively, the top openings of these small metallic nanopillars were capped with Staphylococcus aureus (S. aureus) bacterial cells. High resolution scanning electron microscopy inspection revealed that these bacterial cells were able to cover the top openings of C-shaped pillars within an hour of incubation at 37 °C. Results also demonstrated that capping S. aureus adhesive strengths to the nickel structures are greater than the cell wall cohesive strengths.

Victory or triumph display is a post-contest signal, performed only by winners and not by losers. While much is unknown about its function, there is mounting evidence that victory displays are widespread among animals. However, evidence remains anecdotal in crabs. Sesarmid crabs belonging to the genera Parasesarma and Perisesarma are known to have characteristic stridulatory structures on their chelipeds. In Perisesarma eumolpe, a mangrove crab, stridulation has been anecdotally purported as a triumph display. We examined whether stridulation in P. eumolpe is a victory display and the factors affecting it by staging 17 contest trials among males and investigating the factors influencing stridulations and fight outcome in 55 fights. Using generalised linear mixed-effects models, we find that stridulations were generally performed by winners and after fights, especially when the fights were intense. In addition, stridulation was only observed in the context of a contest, never before or outside of it. Stridulation in P. eumolpe is likely a victory display, and, unlike other forms of victory display described for other species, it appears exclusively used for asserting victory.

Rapid detection of pathogenic bacteria is challenging because conventional methods require long incubation times. Nanoparticles have the potential to detect pathogens before they can cause an infection. Gold nanostars have recently been used for colorimetric biosensors but they typically require surface modification with antibodies or aptamers for cellular detection. Here, CTAB-coated gold nanostars have been used to rapidly (

A phase I trial was conducted to evaluate the safety, tumour and normal tissue localization, pharmacokinetics and radiation dosimetry of Tc-hR3, a humanized monoclonal antibody directed towards the epidermal growth factor receptor, in 12 patients with recurrent or metastatic epithelial malignancies. Patients were injected intravenously with 3.0 mg or 6.0 mg (1010 MBq) of Tc-hR3. Blood and plasma concentrations of radioactivity were measured and a complete 24 h urine collection was obtained. Whole-body images were acquired up to 24 h post-injection and normal organ uptake quantified. Radiation dosimetry was estimated using MIRDose. Safety was evaluated by clinical observation, biochemical/haematological testing and by measuring immune response to Tc-hR3. There were no adverse effects, no changes in biochemical/haematological indices and no immune response to Tc-hR3. Tc-hR3 was rapidly cleared from the blood with a distribution half-life of 10.8+/-3.8 min. The volume of distribution, and clearance, were 180+/-37 ml.kg and 14+/-3 ml.kg.min, respectively. The elimination phase could not be discerned due to increasing blood radioactivity at later times. About 19-24% was excreted in the urine. Normal tissue uptake was mainly in the liver (44-50%), spleen (3-4%) and kidneys (3%). Imaging was positive in one patient with squamous cell carcinoma of the mouth and an involved cervical lymph node. The whole-body radiation dose from Tc-hR3 was 1.34+/-0.02x10 mSv.Bq. We conclude that Tc-hR3 exhibited an excellent safety profile. Future studies to determine the sensitivity and specificity of imaging with Tc-hR3 in a larger group of patients with pre-selection for epidermal growth factor receptor positivity are planned.

This paper proposes a dual-band linear filter assisted envelope memory polynomial model (EMP) devised for analog-RF predistortion (ARFPD) systems. The proposed model consists of two finite-impulse-response (FIR) filters preceding a newly formulated dual-band EMP block in forming the pruned 2D-FIR-EMP model. A linear estimation algorithm is devised to identify the coefficients of the proposed pruned 2D-FIR-EMP model. Furthermore, a proof of concept of the digitally-assisted dual-band ARFPD system based on two RF vector multipliers (RF-VM) built using off-the-shelf (OTS) components is presented. Measurement results obtained using the proposed pruned 2D-FIR-EMP proof-of-concept predistorter has demonstrated excellent linearization results in compensating for the distortions exhibited by a gallium nitride Doherty power amplifier driven by dual-band signals.

To evaluate the ability of trastuzumab (Herceptin) Fab, labelled with (99m)Tc through introduced hydrazinenicotinamide (HYNIC) functionalities, to image HER2/neu-overexpressing human breast cancer xenografts in athymic mice.Fab fragments were produced by immobilized papain digestion of trastuzumab immunoglobulin G (IgG), followed by purification by ultrafiltration. The immunoreactivity of trastuzumab Fab was evaluated by receptor-binding assays against HER2/neu-positive SK-BR-3 human breast cancer cells. Trastuzumab Fab fragments were labelled with (99m)Tc following modification with HYNIC N-hydroxysuccinimide ester. Biodistribution and tumour imaging studies were performed in athymic mice bearing subcutaneous HER2/neu-overexpressing BT-474 human breast cancer xenografts following intravenous injection of 1.1 or 25 MBq of [(99m)Tc]-trastuzumab Fab (30 microg), respectively. The specificity of tumour uptake was assessed by comparison with that of [(99m)Tc]-labelled irrelevant anti-CD33 HuM195 Fab.Trastuzumab Fab was pure and exhibited preserved immunoreactivity towards SK-BR-3 cells (K(d) = 1.6 x 10(-8) M). Modification with HYNIC diminished its receptor-binding affinity fourfold. [(99m)Tc]-trastuzumab Fab localized avidly and specifically in BT-474 xenografts, achieving a tumour uptake of 10.7% of the injected dose (ID) per gram and a tumour to blood (T/B) ratio of 3 : 1 at 24 h. The tumour uptake and T/B ratio for [(99m)Tc]-trastuzumab Fab were significantly higher than those for control [(99m)Tc]-HuM195 Fab (2.6% ID x g(-1) and 0.9 : 1, respectively; P0.05). Tumours were imaged as early as 2 h post-injection of [(99m)Tc]-trastuzumab Fab, but were more clearly visualized at 6 and 24 h post-injection.[(99m)Tc]-HYNIC-trastuzumab Fab localized specifically in HER2/neu-overexpressing human breast cancer xenografts in athymic mice, allowing imaging of the tumours within the useful lifetime of the radionuclide.

An expression vector (pJW4) for a human epidermal growth factor (hEGF)-CH1 fusion protein was constructed by fusing the gene for hEGF with the gene for CH1 of murine IgG1 with/without a peptide linker sequence [(GGGGS)3] and inserting the recombinant gene into vector pGEX2T. Expression vector pGEX2T was transfected into E. coli (BL-21) and hEGF-CH1 expressed by induction of the lac Iq promotor with 50 microM isopropyl beta-D-thiogalactopyranoside (IPTG). hEGF- CH1 fused to glutathione S-transferase (GST) was isolated and purified by affinity chromatography. GST was cleaved using thrombin. SDS-PAGE demonstrated a protein with the expected M(r) (18 kDa) positive for hEGF by Western blot. hEGF-linker-CH1 exhibited preserved binding to A431 (2-3 x 10(6) EGFR/cell) and MDA-MB-468 breast cancer cells (1-2 x 10(6) EGFR/cell). hEGF-CH1 without the linker exhibited poor receptor binding. hEGF-linker-CH1 also exhibited strong binding to soluble EGFR equivalent to that of hEGF. The tumor and normal tissue distribution of hEGF-linker-CH1 labeled with 123I was compared with 123 I-hEGF at 24 h after i.v. injection to mice implanted with s.c. MDA-MB-468 xenografts. Fusion of hEGF with CH1 increased its retention in the blood 14-fold but did not significantly increase tumor uptake. Tumor/blood ratios were higher for hEGF than for hEGF-linker-CH1. We conclude that hEGF is more attractive than hEGF-linker-CH1 for imaging EGFR-positive tumors.

Endometrial cancer (EC) is the most common uterine malignancy in industrialized countries and is the most frequent gynecologic cancer in the United States with an estimated 60,050 new cases in 2016. Traditionally observed in peri-, postmenopausal women, the incidence rate of EC has steadily increased among younger women of reproductive age over the past two decades partially owing to a more sedentary lifestyle and rampant obesity epidemic. Surgery in combination with either radio- and or chemotherapy is commonly curative for the early stage of the disease. However, patients with recurrent or metastatic disease, who only respond poorly to cytotoxic chemotherapy are in desperate need of therapeutic alternatives as are patients of reproductive age. Thus, innovative, safe and more effective therapies are mandated. Several studies have demonstrated the increased expression of various tyrosine kinase receptors involved in the development of EC. We hypothesized that a targeted therapeutic approach using a pan-tyrosine kinase inhibitor would prevent the proliferation and progression of EC. Anlotinib (AL3818) is a multi-targeted receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors 1 to 3 (VEGFR1-3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGFβ), and fibroblast growth factor receptors 1 to 3 (FGFR1-3). We tested a panel of seven human endometrial cancer cell lines (AN3Ca, Ishikawa, HEC1A, HEC1B, KLE, MFE280 and MFE296) to assess the cytotoxicity of anlotinib in vitro. A lower IC50 value was observed in AN3Ca cells (25 nM), a cell line characterized by a high level of expression of an FGFR2 mutant protein, while cell lines expressing FGFR2 wild-type are less sensitive to anlotinib (HEC1A: 33 μM, or HEC1B:36 μM). Somatic mutations of FGFR2 have been observed in 12% of EC, indicating the potential for this drug in a subset of EC patients. In summary, these results suggest improved efficacy of anlotinib for the treatment of ECs expressing an increased level of FGFR2 mutant proteins. The safety and efficacy of anlotinib are currently being evaluated in an orthotopic AN3Ca mouse model of EC. Experimental groups include a tumor bearing control not subjected to any treatment, anlotinib alone, carboplatin/paclitaxel, a combination of anlotinib and carboplatin/paclitaxel. Primary study endpoints include tumor growth retardation, the delayed onset of local metastases as well as reduced toxicity as secondary endpoint. Citation Format: Sebastien Taurin, Chieh-Hsiang Yang, Maria Reyes, Sungpil Cho, Elke A. Jarboe, Theresa L. Werner, Demetrius M. Coombs, Paul Chen, Margit M. Janát-Amsbury. Treatment of endometrial cancer cells with a new small tyrosine kinase inhibitor targeting mutated fibroblast growth factor receptor-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3244. doi:10.1158/1538-7445.AM2017-3244

Ocular pathogens can cause serious damages in the eye leading to severe vision loss and even blindness if left untreated. Identification of pathogens is crucial for administering the appropriate antibiotics in order to gain effective control over ocular infection. Herein, we report a gold nanostar based "chemical nose" for visually identifying ocular pathogens. Using a spectrophotometer and nanostars of different sizes and degrees of branching, we show that the "chemical nose" is capable of identifying the following clinically relevant ocular pathogens with an accuracy of 99%: S. aureus, A. xylosoxidans, D. acidovorans and S. maltophilia. The differential colorimetric response is due to electrostatic aggregation of cationic gold nanostars around bacteria without the use of biomolecule ligands such as aptamers or antibodies. Transmission electron microscopy confirms that the number of gold nanostars aggregated around each bacterium correlates closely with the colorimetric response. Thus, gold nanostars serve as a promising platform for rapid visual identification of ocular pathogens with application in point-of-care diagnostics.

HIV has become one of the most devastating pathogens in human history. Despite fast progress in HIV-related basic research, antiretroviral therapy (ART) remains the most effective method to save AIDS patients' lives. Unfortunately, ART cannot be universally accessed, especially in developing countries, due to the lack of effective treatment monitoring diagnostics. Here, we present an inexpensive, rapid and portable micro-a-fluidic platform, which can streamline the process of an enzyme-linked immunosorbent assay (ELISA) in a fully automated manner for CD4 cell count. The micro-a-fluidic CD4 cell count is achieved by eliminating operational fluid flow via “moving the substrate”, as opposed to “flowing liquid” in traditional ELISA or microfluidic methods. This is the first demonstration of capturing and detecting cells from unprocessed whole blood using the enzyme-linked immunosorbent assay (ELISA) in a microfluidic channel. Combined with cell phone imaging, the presented micro-a-fluidic ELISA platform holds great promise for offering rapid CD4 cell count to scale up much needed ART in resource-constrained settings. The developed system can be extended to multiple areas for ELISA-related assays., Wallace H. Coulter Foundation (Young Investigator Award), National Institutes of Health (U.S.) (RO1A1081534), National Institutes of Health (U.S.) (RO1AI093282), National Institutes of Health (U.S.) (U54EB15408), National Institutes of Health (U.S.) (R21AI087107), Center for Integration of Medicine and Innovative Technology (CIMIT) (U.S. Army Medical Research Acquisition Activity Cooperative Agreements DAMD17-02-2-0006), Center for Integration of Medicine and Innovative Technology (CIMIT) (U.S. Army Medical Research Acquisition Activity Cooperative Agreements W81XWH-07-2-0011), Center for Integration of Medicine and Innovative Technology (CIMIT) (U.S. Army Medical Research Acquisition Activity Cooperative Agreements W81XWH-09-2-0001), United States. Army Medical Research and Materiel Command (research grant), United States. Army. Telemedicine & Advanced Technology Research Center, Brigham and Women's Hospital (Brigham Research Institute for the Bright Futures Award), Brigham and Women's Hospital (Biomedical Research Institute Translatable Technologies & Care Innovation Award)

This chapter provides a review of thermodynamics of liquid films. In particular, film thermodynamics based on the film excess convention is presented. Both the fundamental equation and mechanical equilibrium condition are similar to those of a surface phase in the well-known Gibbsian thermodynamics of surfaces. Experimental techniques for measuring film tension are also reviewed; in particular, Axisymmetric Drop Shape Analysis-Profile (ADSA-P) is introduced. ADSA-P is the only existing technique which is not restricted to spherical drops or bubbles. With ADSA-P, film tension can be measured under both static and dynamic conditions. As a demonstration of ADSA-P, film tension and film rupture of alkanes (hexadecane, tetradecane, and dodecane) at the air–water interface are presented. The film tension measured is found to be equal to the sum of alkane-water interfacial tension and alkane surface tension for hexadecane and tetradecane films. In the case of dodecane films, a slight difference between the film tension and the sum of two surface (interfacial) tensions is observed and can be attributed to the interactions between the two surfaces of the film, which may be quantified by disjoining pressure.

From a thermodynamic point of view, we obtain a general expression of the distortion energy of the lung. From a Maxwell relation of this energy expression, we obtain a relation between the recoil pressure and the surface tension. By using the properties of partial derivatives, we derive a general thermodynamic expression for the surface area. For the two separate cases: (1) fluid-filled lungs (with constant surface tension) and; (2) air-filled lungs (with variable surface tension), we provide explicit expressions for the surface area, the distortion energy and the mechanical work by obtaining the fitting parameters upon comparing the model to the experimental data. In all situations the model predictions are in good agreement with the experimental data. Different from other existing lung models, our model employs the intrinsic relationships of thermodynamics, e.g. Maxwell relations, which provide additional equations and hence reduce the number of the unknowns. Only in obtaining the final explicit expressions, are experimental data used for finding certain parameters in the functional relationships. And this is the only subjectivity of our model.

Recently, Joos proposed a new kinetic model for transfer-controlled surfactant adsorption at liquid interfaces. His model is general, in the sense that the change in interfacial tension is incorporated into adsorption rate descriptions, and its governing kinetic equation can be reduced to various specific expressions for individual situations, such as the Langmuir kinetic equation. Joos developed his kinetic model by simply drawing analogies between adsorption and electrode kinetics, where the rate expression was obtained by using conventional chemical reaction theory. In this paper, we present a quantum statistical formulation for surfactant adsorption kinetics. With the assumption of excited states for molecular adsorption, we derive a rate equation by using Statistical Rate Theory (SRT), which gives the expression for transition probabilities from a first-order perturbation analysis of the Schrodinger equation. This new derivation avoids using the principle of mass action and the law of Arrhenius–Eyring, and hence many empirical assumptions in conventional chemical reaction theory are not needed for describing adsorption kinetics. The resulting rate expression can be reduced to Joos's kinetic equation and hence serves as a confirmation of it. Simplifications of the general rate expression are also presented for specific interfacial situations of near equilibrium and far from equilibrium. A combination of these rate expressions with a surface tension–adsorption relation, e.g. the Frumkin equation, can result in equations that are experimentally accessible. Future work will be concentrated on experimental investigations that may provide further validation of the theory and estimates for the parameters used in the rate expressions, especially the symmetry factor α .

In connection with interfacial tension measurements for n-hexadecane−water under conditions of mutual saturation, we accidentally found an extremely high tension value for the aqueous phase of approximately 80 mJ/m2, using axisymmetric drop shape analysis−profile (ADSA-P) for an air bubble formed in the water phase. This high tension value is that of an alkane film at the air−water interface. From static measurements (the drop surface area kept constant) at 25 ± 0.2 °C, we observed this film tension value to be 80.67 ± 0.06 and 77.20 ± 0.02 mJ/m2 at the 95% confidence level for hexadecane and dodecane films at the air−water interface, respectively. These film tension values were also confirmed in dynamic measurements (the drop surface area continuously increased) for both alkane systems. In addition, film rupture has been demonstrated both in the sudden change in the bubble profile and in the abrupt decrease in the tension value. The alkane film tension measured is approximately equal to the sum of the in...

Line tension is calculated by applying the contact line quadrilateral relation to a dodecane-water-air liquid lens system, where two contact angles are measured through an image analysis scheme. To complement previous measurements on individual lenses [1], contact angles were determined as a function of lens diameter. In order to exclude the possibility of any fluid mechanics or other dynamic effects, the change of lens size was performed at three different rates. No apparent rate dependence of contact angle and line tension can be observed for the three speeds. By reformulating the quadrilateral relation, the lens-size dependence of contact angles can be used in the calculation of line tension. To compute line tension with this scheme, three derivatives need to be obtained in addition to two contact angles and three surface tensions. No computational advantage can be gained over the direct application of the quadrilateral relation; however, the approach used here provides a potentially important approximation in term of a single surface tension and a lens-size dependent contact angle. For the water-dodecane system studied here, the line tension values calculated, by the quadrilateral relation, its reformulation and the simplified quadrilateral relation, are negative and between −1 and −4 × 10−6 J m−1.

The pulsating bubble and the film balance techniques are classical methods for measuring the dynamic surface tension response of surfactant solutions to area changes. Both techniques have advantages and disadvantages, and have been employed to study a variety of surfactant systems. Recently, a motor-controlled syringe has been developed in our laboratory which, when used in conjunction with a drop shape technique known as axisymmetric drop shape analysis (ADSA), is capable of performing many of the experiments traditionally conducted using either the pulsating bubble surfactometer or the film balance. In addition, ADSA has a number of distinct advantages over more conventional approaches. A comparison of these three methodologies is made and new data relating the surface tension response of three concentrations (8, 12 and 16 mM) of sodium dodecyl sulfate (SDS) solutions to surface area changes is reported.

Axisymmetric Drop Shape Analysis has been employed to measure the dynamic surface tension response to a sawtooth-shaped variation in the surface area. Four systems were studied: (a) bovine serum albumin (BSA) aqueous solution; (b) dimethyl sulfoxide (DMSO) added to the BSA aqueous solution; (c) ethyl alcohol (ethanol) added to the BSA aqueous solution; and (d) hepoxilin methyl ester, a lipidic hydroxy epoxide derived from arachidonic acid, dissolved in DMSO and then added to the BSA aqueous solution. In the mixtures of the solutions, competitive adsorption to the surface is revealed between the smaller molecules and the protein molecules, through the change of the pattern in the dynamic surface tension response to the surface area change. In the initial stage of the adsorption, the smaller organic molecules (DMSO, ethanol) diffuse to the surface at a faster rate than the protein molecules, impeding protein adsorption. However, in the cases of DMSO/BSA and ethanol/BSA solutions, the experiment indicates that the small organic molecules are squeezed out of the surface because of the compression/dilation process. After steady state is established, the surface tension pattern shows a skewed shape suggesting a conformational change in the protein. When hepoxilin, a naturally occurring biologically active C20 fatty acid containing a hydroxyl epoxide functionality, is present in the BSA solution, a rather symmetric shape is found in the dynamic surface tension changes, different from the skewed shape found in that of the pure BSA solution. This suggests that hepoxilin molecules interact with the protein, leading to a stabilization of one conformation of the protein molecules at the surface.

The contact line quadrilateral relation is a generalization of the classical Neumann triangle relation that includes the effect of line tension. The relation is derived using a minimum free energy principle that may be graphically represented by a quadrilateral whose four sides consist of three surface tension quantities and a line tension term. When the line tension term vanishes, the quadrilateral relation simplifies to the classical Neumann triangle relation. Applications of the quadrilateral relation are illustrated using several axisymmetric capillary geometries.