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1.
Macromol Rapid Commun ; 41(7): e1900612, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32125047

RESUMO

Water-responsive (WR) materials that strongly swell and shrink in response to changes in relative humidity (RH) have shown a great potential to serve as high-energy actuators for soft robotics and new energy-harvesting systems. However, the design criteria governing the scalable and high-efficiency WR actuation remain unclear, and thus inhibit further development of WR materials for practical applications. Nature has provided excellent examples of WR materials that contain stiff nanocrystalline structures that can be crucial to understand the fundamentals of WR behavior. This work reports that regenerated Bombyx (B.) mori silk can be processed to increase ß-sheet crystallinity, which dramatically increases the WR energy density to 1.6 MJ m-3 , surpassing that of all known natural muscles, including mammalian muscles and insect muscles. Interestingly, the maximum water sorption decreases from 80.4% to 19.2% as the silk's ß-sheet crystallinity increases from 19.7% to 57.6%, but the silk's WR energy density shows an eightfold increase with higher fractions of ß-sheets. The findings of this study suggest that high crystallinity of silk reduces energy dissipation and translates the chemical potential of water-induced pressure to external loads more efficiently during the hydration/dehydration processes. Moreover, the availability of B. mori silk opens up possibilities for simple and scalable modification and production of powerful WR actuators.

2.
ACS Appl Mater Interfaces ; 12(8): 9977-9988, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32013386

RESUMO

The pharmaceutical industry uses surface-active agents (excipients) in protein drug formulations to prevent the aggregation, denaturation, and unwanted immunological response of therapeutic drugs in solution as well as at the air/water interface. However, the mechanism of adsorption, desorption, and aggregation of proteins at the interface in the presence of excipients remains poorly understood. The objective of this work is to explore the molecular-scale competitive adsorption process between surfactant-based excipients and two monoclonal antibody (mAb) proteins, mAb-1 and mAb-2. We use pendant bubble tensiometry to measure the ensemble average adsorption dynamics of mAbs with and without the excipient. The surface tension measurements allow us to quantify the rate at which the molecules "race" to the interface in single-component and mixed systems. These results define the phase space, where coadsorption of both mAbs and excipients occurs onto the air/water interface. In parallel, we use X-ray reflectivity (XR) measurements to understand the molecular-scale dynamics of competitive adsorption, revealing the surface-adsorbed amounts of the antibody and excipient. XR has revealed that at a sufficiently high surface concentration of the excipient, mAb adsorption to the surface and subsurface domains was inhibited. In addition, despite the fact that both mAbs adsorb via a similar mechanistic pathway and with similar dynamics, a key finding is that the competition for the interface directly correlates with the surface activity of the two mAbs, resulting in a fivefold difference in the concentration of the excipient needed to displace the antibody.

3.
Sci Total Environ ; 714: 136553, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31982735

RESUMO

There are 70.8 million forcibly displaced people worldwide, including internally displaced persons, refugees, and asylum seekers. Since mortality rates are highest in the first six months of displacement, the provision of adequate services and infrastructure by relief organizations is critical in this "emergency phase." Environmental health provisions such as adequate water supply, excreta management, solid waste management, and vector control measures are among those essential services. We conducted a systematic scoping review of environmental health in the emergency phase of displacement (the six months following first displacement). A total of 122 publications, comprising 104 peer-reviewed and 18 grey literature publications, met the inclusion criteria. We extracted data relating to environmental health conditions and services, associated outcomes, and information concerning obstacles and recommendations for improving these conditions and services. Despite the fact that most displaced people live outside of camps, publications largely report findings for camps (n = 73, 60%). Water supply (n = 57, 47%) and excreta management (n = 47, 39%) dominate the literature. Energy access (n = 7, 6%), exposure to harsh weather from inadequate shelter (n = 5, 4%), food hygiene and safety (n = 4, 3%), indoor air quality (n = 3, 3%), menstrual hygiene management (n = 2, 2%), dental hygiene (n = 2, 2%), and ambient air quality (n = 1, 1%) are relatively understudied. The most common health outcome attributed to inadequate environmental conditions in the included publications is diarrhea (n = 43, 35%). We found that organizations and governments often embrace their own standards, however we call for policymakers to adopt standards no less rigorous than Sphere for the emergency phase of displacement. Although other reviews examine water, sanitation, and hygiene interventions in emergencies, this is the first systematic review of environmental health more broadly in the first six months of displacement.

4.
ACS Appl Mater Interfaces ; 12(4): 5128-5135, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31885259

RESUMO

The adhesion force and contact angle of gold-capped silica Janus particles and plain silica particles at an air-water interface are studied via colloidal atomic force microscopy. Particles are attached to cantilevers at various orientations, and wetting properties of the gold surface are varied through modification with dodecanethiol. Thiol modification increases the hydrophobicity of the gold surface, thereby increasing the difference between the contact angles of the gold hemisphere and the silica hemisphere and, thus, increasing the degree of amphiphilicity of the Janus particle. Subsequently, the colloidal probe is pushed into a stationary bubble from the water phase followed by retraction back into the water phase. Adhesion force is found to be higher for Janus particles than isotropic silica particles, regardless of orientation of the anisotropic hemisphere. Particles with their polar half oriented toward the water and apolar half facing the air show an increase in adhesion force and contact angle as the degree of amphiphilicity of the particles increases. For particles of the reverse orientation, no significant difference is observed as wetting properties change. Both adhesion force and contact angle display an inverse relationship with a cap angle for particles with a higher degree of amphiphilicity. These results are of importance for using Janus particles to stabilize interfaces as well as for understanding the equilibrium height of Janus particles at the interface, which will impact capillary interactions and thus self-assembly.

5.
Langmuir ; 35(48): 15813-15824, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269790

RESUMO

Langmuir monolayers of silica/gold Janus particles with two different degrees of amphiphilicity have been examined to study the significance of particle surface amphiphilicity on the structure and mechanical properties of the interfacial layers. The response of the layers to the applied compression provides insight into the nature and strength of the interparticle interactions. Different collapse modes observed for the interfacial layers are linked to the amphiphilicity of Janus particles and their configuration at the interface. Molecular dynamics simulations on nanoparticles with similar contact angles provide insight on the arrangement of particles at the interface and support our conclusion that the interfacial configuration and collapse of anisotropic particles at the air/water interface are controlled by particle amphiphilicity.

6.
Biomacromolecules ; 20(9): 3340-3351, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31356057

RESUMO

Thermoresponsive hydrogels are used for an array of biomedical applications. Lower critical solution temperature-type hydrogels have been observed in nature and extensively studied in comparison to upper critical solution temperature (UCST)-type hydrogels. Of the limited protein-based UCST-type hydrogels reported, none have been composed of a single coiled-coil domain. Here, we describe a biosynthesized homopentameric coiled-coil protein capable of demonstrating a UCST. Microscopy and structural analysis reveal that the hydrogel is stabilized by molecular entanglement of protein nanofibers, creating a porous matrix capable of binding the small hydrophobic molecule, curcumin. Curcumin binding increases the α-helical structure, fiber entanglement, mechanical integrity, and thermostability, resulting in sustained drug release at physiological temperature. This work provides the first example of a thermoresponsive hydrogel comprised of a single coiled-coil protein domain that can be used as a vehicle for sustained release and, by demonstrating UCST-type behavior, shows promise in forging a relationship between coiled-coil protein-phase behavior and that of synthetic polymer systems.

7.
J Am Coll Radiol ; 16(4 Pt B): 624-630, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30947897

RESUMO

In this article, the authors review the evolving state of diversity in the field of radiology. The authors discuss several early and recent historical legislative milestones that increased the equitable delivery of health care in the United States, such as Title VI of the Civil Rights Act of 1964, which ensured that funds for Medicare reimbursement would be available only to desegregated hospitals. Furthermore, the authors examine the current state of diversity and representation in radiology, in which underrepresented minorities represent 8.3% of training and practicing radiologists, and women represent 27.8% of radiologists. Finally, the authors present arguments for diversity in the current medical education system, analyze hurdles to increasing representation in radiology, and consider the future of diversity and inclusiveness in the field.


Assuntos
Diversidade Cultural , Disparidades nos Níveis de Saúde , Grupos Minoritários/estatística & dados numéricos , Médicas/tendências , Radiologistas/organização & administração , Recursos Humanos/organização & administração , Escolha da Profissão , Direitos Civis , Feminino , Humanos , Masculino , Motivação , Estados Unidos
8.
AAPS J ; 21(3): 44, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30915582

RESUMO

Biologic products encounter various types of interfacial stress during development, manufacturing, and clinical administration. When proteins come in contact with vapor-liquid, solid-liquid, and liquid-liquid surfaces, these interfaces can significantly impact the protein drug product quality attributes, including formation of visible particles, subvisible particles, or soluble aggregates, or changes in target protein concentration due to adsorption of the molecule to various interfaces. Protein aggregation at interfaces is often accompanied by changes in conformation, as proteins modify their higher order structure in response to interfacial stresses such as hydrophobicity, charge, and mechanical stress. Formation of aggregates may elicit immunogenicity concerns; therefore, it is important to minimize opportunities for aggregation by performing a systematic evaluation of interfacial stress throughout the product development cycle and to develop appropriate mitigation strategies. The purpose of this white paper is to provide an understanding of protein interfacial stability, explore methods to understand interfacial behavior of proteins, then describe current industry approaches to address interfacial stability concerns. Specifically, we will discuss interfacial stresses to which proteins are exposed from drug substance manufacture through clinical administration, as well as the analytical techniques used to evaluate the resulting impact on the stability of the protein. A high-level mechanistic understanding of the relationship between interfacial stress and aggregation will be introduced, as well as some novel techniques for measuring and better understanding the interfacial behavior of proteins. Finally, some best practices in the evaluation and minimization of interfacial stress will be recommended.

9.
Phys Chem Chem Phys ; 20(30): 20287-20295, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30039819

RESUMO

We examine the dynamics of the sol-gel transition for end-functionalized linear- and 4-arm-peptides bioconjugated to poly-ethylene glycol (PEG) in aqueous environments with increasingly chaotropic (Cl- < Br- < I-) anions. A 23-amino acid peptide sequence is rationally designed to self-assemble upon folding into the ordered α-helical conformation due to the hydrophobic effect. We use Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) to quantify the ensemble average reversible secondary structure transitions as a function of electrolyte concentration and specific ion effects along the Hofmeister series. Subsequently, microrheology is used to quantify the kinetics of the gelation process, as it relates to folding and specific ion interactions. Our key findings were non-intuitive. We observe the faster evolution of the gel transitions in systems with more chaotropic anions. For our peptides in aqueous solution, "water-structuring" ions yield faster assembly behavior with a viscoelastic exponent, n, closer to unity representing self-assemblies that are Rouse-like. In contrast, ions that are "water-breaking" resulted in smaller viscoelastic exponents where self-assembly dynamics result in a viscoelastic exponent that suggests polymer entanglements.


Assuntos
Ânions/química , Géis/química , Peptídeos/química , Polietilenoglicóis/química , Sequência de Aminoácidos , Brometos/química , Cloretos/química , Iodetos/química , Cinética , Transição de Fase , Conformação Proteica , Reologia , Espectroscopia de Infravermelho com Transformada de Fourier , Substâncias Viscoelásticas/química , Água/química
10.
Biomacromolecules ; 19(5): 1552-1561, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29544048

RESUMO

Recombinant methods have been used to engineer artificial protein triblock polymers composed of two different self-assembling domains (SADs) bearing one elastin (E) flanked by two cartilage oligomeric matrix protein coiled-coil (C) domains to generate CEC. To understand how the two C domains improve small molecule recognition and the mechanical integrity of CEC, we have constructed CL44AECL44A, which bears an impaired CL44A domain that is unstructured as a negative control. The CEC triblock polymer demonstrates increased small molecule binding and ideal elastic behavior for hydrogel formation. The negative control CL44AECL44A does not exhibit binding to small molecule and is inelastic at lower temperatures, affirming the favorable role of C domain and its helical conformation. While both CEC and CL44AECL44A assemble into micelles, CEC is more densely packed with C domains on the surface enabling the development of networks leading to hydrogel formation. Such protein engineered triblock copolymers capable of forming robust hydrogels hold tremendous promise for biomedical applications in drug delivery and tissue engineering.


Assuntos
Proteína de Matriz Oligomérica de Cartilagem/química , Elasticidade , Elastina/química , Motivos de Aminoácidos , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Elastina/metabolismo , Micelas , Ligação Proteica , Domínios Proteicos , Estresse Mecânico
11.
Nano Lett ; 18(4): 2564-2570, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29584938

RESUMO

Long-range interactions often proceed as a sequence of hopping through intermediate, statistically favored events. Here, we demonstrate predictable mechanical dynamics of particles that arise from the Lorentz force between plasmons. Even if the radiation is weak, the nonconservative Lorentz force produces stable locations perpendicular to the plasmon oscillation; over time, distinct patterns emerge. Experimentally, linearly polarized light illumination leads to the formation of 80 nm diameter Au nanoparticle chains, perpendicularly aligned, with lengths that are orders of magnitude greater than their plasmon near-field interaction. There is a critical intensity threshold and optimal concentration for observing self-assembly.

13.
ACS Omega ; 2(11): 8308-8312, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31457370

RESUMO

1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC) is a commonly used reagent for bioconjugation and peptide synthesis. Both EDC and the corresponding urea derivative, 1-(3-dimethylaminopropyl)-3-ethylurea (EDU), are achiral. As the reagent is active in aqueous solutions, it is a common choice for the study of evolving secondary structural changes via circular dichroism. This work highlights the effect of EDU on spectropolarimetric measurements, namely, the problematic absorption profile at low wavelengths (190-220 nm). We demonstrate that EDU is capable of erroneously indicating structural changes, particularly loss of α-helical character, through masking of the characteristic minimum at 208 nm. However, if the concentrations of the EDU in the sample are known, then this effect can be anticipated and calculations of secondary structure can be adjusted to avoid the impacted wavelengths. Impacts of EDU in a sample are compared to those of standard urea, which, by contrast, is commonly used as a denaturant in circular dichroism studies without issue.

14.
Bioconjug Chem ; 27(8): 1813-21, 2016 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-27463763

RESUMO

The linker between the targeting moiety and the nanoparticle is often overlooked when engineering targeted drug delivery vehicles. We hypothesized that pH-triggered conformational changes of an elastin-like peptide (ELP) linker, with repeating VPGVG sequences, could alter the binding affinity of the well-established targeting moiety arginine-glycine-aspartic acid (RGD), which is known to enhance the delivery of nanoparticles to tumor cells via integrin overexpression. The pH change from blood (pH 7.4) to the tumor environment (pH 6) was used to elicit a conformational change in the ELP linker, as described by circular dichroism. Atomic force microscopy confirmed that RGD-ELP resulted in stronger adhesion to both MDA-MB-231 and HCC1806 breast cancer cells at pH 6 relative to pH 7.4. No change in adhesion force was measured as a function of pH for the non-neoplastic MCF-10A cell line and the nontargeting GDR-ELP peptide. This translated to significant binding and uptake of RGD-ELP modified liposomes at pH 6.0 relative to pH 7.4. These results indicate that the pH-triggered conformational structure of the ELP linker shifts RGD-mediated cancer cell targeting from non-active (pH 7.4) to active (pH 6). The reversible shift in ELP secondary structure may be used to engineer targeted drug delivery vehicles with tunable uptake.


Assuntos
Elastina/química , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Sequência de Aminoácidos , Adesão Celular , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Integrina alfa5beta1/química , Integrina alfa5beta1/metabolismo , Integrina alfaVbeta3/química , Integrina alfaVbeta3/metabolismo , Lipossomos , Modelos Moleculares , Nanopartículas/química , Fragmentos de Peptídeos/toxicidade , Estrutura Secundária de Proteína , Transporte Proteico
15.
J Am Chem Soc ; 137(49): 15370-3, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26588066

RESUMO

The compressional instability of particle-laden air/water interfaces is investigated with plain and surface-anisotropic (Janus) particles. We hypothesize that the amphiphilic nature of Janus particles leads to both anisotropic particle-particle and particle-interface interactions that can yield particle films with unique collapse mechanisms. Analysis of Langmuir isotherms and microstructural characterization of the homogeneous polystyrene particle films during compression reveal an interfacial buckling instability followed by folding, which is in good agreement with predictions from classical elasticity theory. In contrast, Janus particle films exhibit a different behavior during compression, where the collapse mode occurs through the subduction of the Janus particle film. Our results suggest that particle-laden films comprised of surface-anisotropic particles can be engineered to evolve new material properties.

16.
Soft Matter ; 11(33): 6604-12, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26198202

RESUMO

The interfacial adsorption of proteins in surfactant laden systems occurs both in nature and industrial processing, yet much of the fundamental behavior behind these systems is still not well understood. We report the development of a system that monitors optical transitions of a liquid-crystalline/aqueous interface to examine the dynamics of adsorption of two rationally designed model peptide molecules. The two molecules synthesized in this study were both designed to become surface-active upon folding and contain the same net charge of +3, but one of the peptides, K-2.5, has its three charges separated by 2.5 amino acids as compared to K-6.0, which has its three charges separated by 6 amino acids. Our study examines the roles that surfactant adsorption, peptide charge distribution and secondary structure have on the relative adsorption dynamics of these two models peptides onto a fluid/fluid interface. Using the optical detection of molecular adsorption and image analysis of these events, we obtain quantitative information about the dynamics as a function of the charge spacing and initial peptide concentration. We show that both peptides initially follow a diffusion-limited adsorption model onto the interface. Additionally, our results suggest that the K-6.0 peptides demonstrate enhanced adsorption kinetics, where the enhanced rates are a consequence of the well-folded adsorbed state and spatial distribution on the surface. These findings provide further insights into the role that charge spacing has on secondary structure and subsequently the dynamics of adsorption, while developing a versatile system capable of extracting quantitative information from a simple inexpensive optical system.


Assuntos
Cristais Líquidos/química , Peptídeos/química , Adsorção , Sequência de Aminoácidos , Cetrimônio , Compostos de Cetrimônio/química , Dicroísmo Circular , Difusão , Microscopia de Polarização/instrumentação , Microscopia de Polarização/métodos , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Propriedades de Superfície , Tensoativos/química
17.
Langmuir ; 31(28): 7764-75, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26099031

RESUMO

Colloidal particles can bind to fluid interfaces with a capillary energy that is thousands of times the thermal energy. This phenomenon offers an effective route to emulsion and foam stabilization where the stability is influenced by the phase behavior of the particle-laden interface under deformation. Despite the vast interest in particle-laden interfaces, the key factors that determine the collapse of such an interface under compression have remained relatively unexplored. In this study, we illustrate the significance of the particle surface wettability and presence of electrolyte in the subphase on interparticle interactions at the interface and the resulting collapse mode. Various collapse mechanisms including buckling, particle expulsion, and multilayer formation are reported and interpreted in terms of particle-particle and particle-interface interactions.


Assuntos
Pressão , Dióxido de Silício/química , Molhabilidade , Eletrólitos/química , Nanopartículas/química
19.
J Neurointerv Surg ; 7(4): 309-12, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24589819

RESUMO

In 1966, The American Medical Association (AMA) working with multiple major medical specialty societies developed an iterative coding system for describing medical procedures and services using uniform language, the Current Procedural Terminology (CPT) system. The current code set, CPT IV, forms the basis of reporting most of the services performed by healthcare providers, physicians and non-physicians as well as facilities allowing effective, reliable communication among physician and other providers, third parties and patients. This coding system and its maintenance has evolved significantly since its inception, and now goes well beyond its readily perceived role in reimbursement. Additional roles include administrative management, tracking new and investigational procedures, and evolving aspects of 'pay for performance'. The system also allows for local, regional and national utilization comparisons for medical education and research. Neurointerventional specialists use CPT category I codes regularly--for example, 36,215 for first-order cerebrovascular angiography, 36,216 for second-order vessels, and 37,184 for acute stroke treatment by mechanical means. Additionally, physicians add relevant modifiers to the CPT codes, such as '-26' to indicate 'professional charge only,' or '-59' to indicate a distinct procedural service performed on the same day.


Assuntos
Current Procedural Terminology , American Medical Association , Health Insurance Portability and Accountability Act/tendências , Humanos , Reembolso de Incentivo/tendências , Estados Unidos
20.
J Neurointerv Surg ; 6(9): 712-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25179635

RESUMO

Carotid and cerebral angiography have been a mainstay of neurointerventional and neuroradiologic practice for years. Centers for Medicare and Medicaid Services (CMS) and Relative Value Scale Update Committee (RUC) initiatives have compelled the professional societies to bundle component codes under threat of unilateral CMS revision and revaluation. Code bundling usually results in a decrease in the professional Relative Value Unit (RVU) valuation, and thus the MD reimbursement. The year 2013 saw a dramatic revision to the Current Procedural Terminology (CPT) code set that defines carotid and cerebral procedures. This paper reviews the process that led to that code set being revised and estimates the impact on professional reimbursement. We show the current and previous carotid angiography CPT codes and use clinical examples to assess professional RVU valuation before and after code revision.


Assuntos
Artérias Carótidas/patologia , Doenças das Artérias Carótidas/diagnóstico , Angiografia Cerebral/métodos , Legislação Médica/tendências , Humanos , Reembolso de Seguro de Saúde , Medicare , Mecanismo de Reembolso , Escalas de Valor Relativo , Estados Unidos
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