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OBJECTIVES: Explore pediatric staff experiences administering the second influenza vaccine dose. STUDY DESIGN: Qualitative focus groups/interviews. METHODS: As part of the National Institutes of Health-funded Flu2Text randomized control trial of text message reminders for second influenza vaccine dose, we conducted seven focus groups and four individual interviews (n = 39 participants total) with clinicians and staff from participating practices from the American Academy of Pediatrics' Pediatric Research in Office Settings (PROS) Network. Of 37 participating practices, 10 were selected through stratified sampling of practices with highest (n = 5) and lowest (n = 5) randomized controlled trial effect sizes. A semi-structured discussion guide included questions that addressed parental, practice, and health system barriers/facilitators to second influenza vaccine dose administration. Using the Systems Model of Clinical Preventive Care as a conceptual framework, two investigators independently coded transcripts (Κ = 0.86, high agreement) with NVivo 12 Plus. Coding inconsistencies were resolved by consensus. RESULTS: Clinicians/staff reported that administering the second influenza vaccine dose in a season was more complex than other childhood vaccines. They highlighted parental uncertainty about the need for the second dose and the difficulty and inconvenience of bringing children back to the office as important barriers. Caregiver-staff relationships were perceived as helpful in getting children vaccinated with their second dose and vaccine reminders were seen as important cues-to-action. CONCLUSIONS: Ensuring receipt of two doses of the influenza vaccine in a given season presents unique challenges. Themes identified provide a framework for understanding opportunities to bolster second dose receipt, including explaining why two doses are needed, offering flexible hours for vaccination, and sending vaccine reminders.
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Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined skin and blood samples from twelve subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a proliferative fraction of lymphatic endothelial cells, and the second represented an angiogenic population of vascular endothelial tip cells. Both infected clusters contained cells expressing lytic and latent KSHV genes. Novel cellular biomarkers were identified in the KSHV infected cells, including the sodium channel SCN9A. The number of KSHV positive tumor cells was found to be in the 6% range in HIV-associated KS, correlated inversely with tumor-infiltrating immune cells, and was reduced in biopsies from HIV-negative individuals. T-cell receptor clones were expanded in KS tumors and blood, although in differing magnitudes. Changes in cellular composition in KS tumors were identified in subjects treated with antiretroviral therapy alone, or immunotherapy. These studies demonstrate the feasibility of single cell analyses to identify prognostic and predictive biomarkers. Author Summary: Kaposi sarcoma (KS) is a malignancy caused by the KS-associated herpesvirus (KSHV) that causes skin lesions, and may also be found in lymph nodes, lungs, gastrointestinal tract, and other organs in immunosuppressed individuals more commonly than immunocompetent subjects. The current study examined gene expression in single cells from the tumor and blood of these subjects, and identified the characteristics of the complex mixtures of cells in the tumor. This method also identified differences in KSHV gene expression in different cell types and associated cellular genes expressed in KSHV infected cells. In addition, changes in the cellular composition could be elucidated with therapeutic interventions.
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We investigate the effects of non-magnetic disorder in a hybridized two-dimensional two-orbital s-wave superconductor (SC) model. The situation in which electronic orbitals overlap such that the hybridizationVi,jamong them is antisymmetric, under inversion symmetry, was taken into account. The on-site disorder is given by a random impurity potentialW. We find that while the random disorder acts to the detriment of superconductivity, hybridization proceeds to favor it. Accordingly, hybridization plays an important role in two-orbital models of superconductivity, in order to hold the long-range order against the increase of disorder. This makes the present model eligible to describe real materials, since the hybridization may be induced by pressure or doping. In addition, the regime from moderate to strong disorder reveals that the system is broken into SC islands with correlated local order parameters. These correlations persist to distances of several order lattice spacing which corresponds to the size of the SC-Islands.
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Cycadales is highly endangered and one of the oldest dioecious gymnosperm lineages, making their reproductive biology highly relevant to conservation efforts and our understanding of the impact of dioecy, yet cycad reproductive ecophysiology is poorly understood. We examined how the costs associated with reproduction may impact basic physiological variation in cycad species. Specifically, we measured traits related to functional morphology and photosynthetic physiology in sterile and fertile staminate plants ('males') of Zamia portoricensis. Light response curves showed that sterile plants had greater light-use efficiency and maximum photosynthetic capacity per area compared with fertile plants. However, fertile and sterile plants exhibited similar respiration rates. We found significantly more nitrogen in leaves of fertile individuals, but similar nitrogen isotope composition and no differences in carbon content between sterile and fertile individuals. Despite having lower leaf-level photosynthetic rates, fertile plants had greater canopy-level photosynthesis than sterile plants, which was achieved by increasing leaf number and total leaf area. Our data suggest that sterile individuals may have greater light demands relative to fertile individuals, and fertile individuals may have greater nitrogen demands, which may be critical for successful reproductive events in staminate plants of the endangered cycad, Z. portoricensis.
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Introduction: In highly autonomous driving scenarios, it is critical to identify strategies to accelerate reaction times since drivers may take too long to take over control of the vehicle. Previous studies reported that an Acoustic Startling Pre-Stimulus (ASPS, i.e., a loud warning preceding an action) accelerated reaction times in simple ankle flexion exercises. Methods: In this study, we examined if an ASPS warning leads to shorter takeover reaction times in a sled-simulated evasive swerving maneuver. Twenty-eight participants (seven male adults, seven male teenagers, seven female adults, and seven female teenagers) were instructed to align a marker on the steering wheel with a marker on a lateral post as fast as they could as soon as the lateral sled perturbation (0.75 g) started. Four conditions were examined: with and without an ASPS (105 dB, played 250 ms before sled perturbation for 40 ms), and with and without a secondary task (i.e., texting). A catch trial (ASPS only) was used to minimize anticipation. Human kinematics were captured with an 8-camera 3D motion capture system. Results: Results showed that the drivers' hands lifted towards the steering wheel more quickly with the ASPS (169 ± 55 ms) than without (194 ± 46 ms; p = 0.01), and that adult drivers touched the steering wheel quicker with the ASPS (435 ± 54 ms) than without (470 ± 33 ms; p = 0.01). Similar findings were not observed for the teen drivers. Additionally, female drivers were found to lift their hands towards the steering wheel faster than male drivers (166 ± 58 ms vs. 199 ± 36 ms; p = 0.009). Discussion: Our findings suggest that the ASPS may be beneficial to accelerate driver reaction times during the initiation of a correction maneuver, and that autonomous vehicle warnings may need to be tailored to the age and sex of the driver.
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OBJECTIVE: Pre-pretensioner (PPT) seatbelts have been found to be effective in controlling vehicle occupants' motion response to disturbances in optimally positioned occupants, but it is not clear how the PPT performs when the occupant is initially forward leaning. Previous work demonstrated that an acoustic startling pre-stimulus (ASPS) reduced trunk out-of-position in sled-simulated pre-crash maneuvers. Therefore, the aim of this study was to determine if coupling the PPT with the ASPS could reduce the needed magnitude and rate of belt tension of the PPT to reposition forward leaning occupants to their optimal position within the seatbelt. METHODS: Sixteen belt-restrained adult human volunteers (8 males and 8 females) restrained by a 3-point seatbelt on a vehicle seat in a forward leaning posture on a sled simulating pre-crash braking (approx. 1 g of maximum acceleration and 0.3 s duration) were exposed to sled perturbations with three belt configurations (low and high force PPT and no PPT), and two warning conditions (ASPS and no-ASPS). Head and trunk positions were extracted from the 3D motion-capture data. Repeated measure ANOVAs were used to understand the effect of sex, PPT, ASPS, and repetition on head and trunk positions. A survival analysis was also performed to understand the probability of the occupants moving rearward in the different conditions. RESULTS: The probability of the head and trunk to move rearward from the initial position was greater with the PPT than without the PPT (p = 0.01) and with the high force level than the low force level (p = 0.01). The interaction effect of ASPS x PPT showed that with no PPT, there was a greater probability for the head to move rearward from the initial position with ASPS than without ASPS (p < 0.03). The trunk shows a similar trend to the head, but the ASPS vs no-ASPS differences were not statistically significant (p = 0.06). No sex differences were found. CONCLUSIONS: The PPT, particularly the high level, may be an effective countermeasure on its own to reduce trunk and head out-of-position in forward leaning postures in pre-crash scenarios. The ASPS reduced the occupants' head forward position when the PPT was not available.
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Accidentes de Tránsito , Cinturones de Seguridad , Masculino , Adulto , Femenino , Humanos , Accidentes de Tránsito/prevención & control , Fenómenos Biomecánicos , Aceleración , Voluntarios SanosRESUMEN
Chinese yew (Taxus wallichiana var. mairei) is ranked as a rare and endangered plant of first-grade protection of China. It has been widely cultivated in 17 provinces of China over the past few decades. However, little is known about the dispersion, rewilding, and ecological influence of Chinese yew's offspring during cultivation. Here, we report a noteworthy case of this species, via ex situ conservation, which has successfully spread into different secondary forests, thus forming a stable regenerating population in eastern China. The establishment of this yew population, which has > 900 individuals and 7 ha area, can be ascribed to two key ecological factors: (1) secondary forest near the parent yews that provided suitable microhabitats in which progeny yews could germinate and grow, and (2) seed-foraging and transportation by native birds. Thus, this case may offer a pathway for conserving endangered Chinese Taxus species, which can attract frugivorous birds to disperse their seeds. In addition, it is necessary to monitor the growth performance of progeny population in the field.
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A proposal to study topological models beyond the standard topological classification and that exhibit breakdown of Lorentz invariance is presented. The focus of the investigation relies on their anisotropic quantum critical behavior. We study anisotropic effects on three-dimensional (3D) topological models, computing their anisotropic correlation length critical exponent [Formula: see text] obtained from numerical calculations of the penetration length of the zero-energy surface states as a function of the distance to the topological quantum critical point. A generalized Weyl semimetal model with broken time-reversal symmetry is introduced and studied using a modified Dirac equation. An approach to characterize topological surface states in topological insulators when applied to Fermi arcs allows to capture the anisotropic critical exponent [Formula: see text]. We also consider the Hopf insulator model, for which the study of the topological surface states yields unusual values for [Formula: see text] and for the dynamic critical exponent z. From an analysis of the energy dispersions, we propose a scaling relation [Formula: see text] and [Formula: see text] for [Formula: see text] and z that only depends on the Hopf insulator Hamiltonian parameters p and q and the axis direction [Formula: see text]. An anisotropic quantum hyperscaling relation is also obtained.
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Global conservation policy and action have largely neglected protecting and monitoring genetic diversity-one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species' adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity.
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OBJECTIVE: Characteristics of specific Automatic Emergency Braking (AEB) pulses can result in increased motion of the occupant, which can lead to the occupant being out-of-position such that when a crash occurs protection may be compromised. Quantifying these variations across the modern fleet is crucial to understand the loading environment to which vehicle occupants are exposed. Therefore, we categorized the AEB pulses based on acceleration pulse features such as deceleration magnitude, jerk, and ramp time. METHODS: A total of 2278 AEB vehicle tests (years 2013-2019) were extracted from the Insurance Institute for Highway Safety (IIHS) database and analyzed. The following pulse characteristics were extracted: Jerk (g/s), Ramp-time (s), and Maximum deceleration (g). A subset of tests in which the tested vehicle did not contact the foam target (n = 1665) was analyzed further, with the following additional variables extracted: Deceleration time (s), Steady-state deceleration (g), and Duration (s). Other non-pulse related features were also considered: Test speed (20 and 40 km/h), Curb weight (Kg), and Vehicle Model Year. Using machine learning methods, the pulses were categorized into clusters. One-way ANOVAs for continuous variables and X2 for categorical features were used to assess differences between clusters (p ≤ 0.05). RESULTS: Using the entirety of the AEB vehicle tests extracted (n = 2278), a total of 3 clusters were selected. The three clusters showed significantly different Jerk, Ramp-time, and Maximum deceleration (p < 0.001). Target contact decreased in AEB tests with more recent vehicle model years (rate of contact 66% in 2014 vs 1.7% in 2019). In one cluster, Jerk and Maximum deceleration increased with vehicle model year. Using the subset of tests in which there was no contact with the foam target (n = 1665), 4 categories of pulses were selected. In both sets of clusters, Ramp-time and Jerk showed moderate inverse correlation (r = -0.7), while all other features showed a low correlation. CONCLUSIONS: These results show that AEB technology improved over the years in obstacle avoidance. The identification of AEB pulse clusters is important in order to describe distinct approaches to achieving AEB and to be able to reproduce representative AEB pulses in the laboratory and understand the influences of those pulses on occupants' motion.
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Desaceleración , Equipos de Seguridad , Aceleración , Accidentes de Tránsito/prevención & control , Humanos , TecnologíaRESUMEN
Growth dynamics of pachycaulous stems of arborescent cycad plants are not well understood, and most observations have been made in cultivated garden plants. We studied Cycas micronesica plants in Guam, Tinian, and Yap to understand the influences of geography, plant size, sex, and herbivory on stem growth. We also determined the changes in demography of Guam's population after 15 years of damage by non-native insect herbivores. The height increment (HI) was similar for plants within the height range from 100 cm to more than 600 cm, so the relative growth rate declined with height. Female tree HI was 68% of male tree HI, and Yap tree HI was 87% of Guam tree HI. Chronic herbivory by non-native insect herbivores caused a mean 44% decline in HI. Plants in managed gardens grew more rapidly than plants in a wild habitat. The HI was used to estimate that Guam has experienced a complete loss of ≈70 y of demographic depth resulting from the selective mortality of small plants since 2005. When future conservation interventions successfully mitigate the ubiquitous biological threats, our HI may be useful for empirically quantifying recovery of plant health.
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Conservación de los Recursos Naturales , Cycas/anatomía & histología , Cycas/crecimiento & desarrollo , Demografía , Tallos de la Planta/anatomía & histología , Árboles/anatomía & histologíaRESUMEN
BACKGROUND: The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells and are under clinical trial development. However, the optimisation and standardisation of neoantigen identification, as well as its delivery as immunotherapy are needed to increase tumour-specific T-cell responses and, thus, the clinical efficacy of current cancer immunotherapies. METHODS: In this recommendation article, launched by the European Society for Medical Oncology (ESMO), we outline and discuss the available framework for neoantigen prediction and present a systematic review of the current scientific evidence. RESULTS: A number of computational pipelines for neoantigen prediction are available. Most of them provide peptide major histocompatibility complex (MHC) binding affinity predictions, but more recent approaches incorporate additional features like variant allele fraction, gene expression, and clonality of mutations. Neoantigens can be predicted in all cancer types with high and low tumour mutation burden, in part by exploiting tumour-specific aberrations derived from mutational frameshifts, splice variants, gene fusions, endogenous retroelements and other tumour-specific processes that could yield more potently immunogenic tumour neoantigens. Ongoing clinical trials will highlight those cancer types and combinations of immune therapies that would derive the most benefit from neoantigen-based immunotherapies. CONCLUSIONS: Improved identification, selection and prioritisation of tumour-specific neoantigens are needed to increase the scope of benefit from cancer vaccines and adoptive T-cell therapies. Novel pipelines are being developed to resolve the challenges posed by high-throughput sequencing and to predict immunogenic neoantigens.
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Vacunas contra el Cáncer , Neoplasias , Humanos , Antígenos de Neoplasias/genética , Inmunoterapia , Oncología Médica , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisión , Guías de Práctica Clínica como AsuntoRESUMEN
Effectively conserving biodiversity with limited resources requires scientifically informed and efficient strategies. Guidance is particularly needed on how many living plants are necessary to conserve a threshold level of genetic diversity in ex situ collections. We investigated this question for 11 taxa across five genera. In this first study analysing and optimizing ex situ genetic diversity across multiple genera, we found that the percentage of extant genetic diversity currently conserved varies among taxa from 40% to 95%. Most taxa are well below genetic conservation targets. Resampling datasets showed that ideal collection sizes vary widely even within a genus: one taxon typically required at least 50% more individuals than another (though Quercus was an exception). Still, across taxa, the minimum collection size to achieve genetic conservation goals is within one order of magnitude. Current collections are also suboptimal: they could remain the same size yet capture twice the genetic diversity with an improved sampling design. We term this deficiency the 'genetic conservation gap'. Lastly, we show that minimum collection sizes are influenced by collection priorities regarding the genetic diversity target. In summary, current collections are insufficient (not reaching targets) and suboptimal (not efficiently designed), and we show how improvements can be made.
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Biodiversidad , Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Animales , Clasificación , Plantas , Tamaño de la MuestraRESUMEN
Maintaining a living plant collection is the most common method of ex situ conservation for plant species that cannot be seed banked (i.e., exceptional species). Viability of living collections, and their value for future conservation efforts, can be limited without coordinated efforts to track and manage individuals across institutions. Using a pedigree-focused approach, the zoological community has established an inter-institutional infrastructure to support long-term viability of captive animal populations. We assessed the ability of this coordinated metacollection infrastructure to support the conservation of 4 plant species curated in living collections at multiple botanic gardens around the world. Limitations in current practices include the inability to compile, share, and analyze plant collections data at the individual level, as well as difficulty in tracking original provenance of ex situ material. The coordinated metacollection framework used by zoos can be adopted by the botanical community to improve conservation outcomes by minimizing the loss of genetic diversity in collections. We suggest actions to improve ex situ conservation of exceptional plant species, including developing a central database to aggregate data and track unique individuals of priority threatened species among institutions and adapting a pedigree-based population management tool that incorporates life-history aspects unique to plants. If approached collaboratively across regional, national, and global scales, these actions could transform ex situ conservation of threatened plant species.
Aplicación del Modelo Zoológico a la Conservación de Especies Excepcionales de Plantas Amenazadas Resumen El mantenimiento de una colección de plantas vivas es el método más común para de conservación ex situ para especies de plantas que no pueden almacenarse en bancos de semillas (i. e., especies excepcionales). La viabilidad de las colecciones vivientes, junto con el valor que representan para los futuros esfuerzo de conservación, puede estar limitada si no existen esfuerzos coordinados para rastrear y manejar a los individuos entre las instituciones. Mediante una estrategia enfocada en el linaje, la comunidad de zoológicos ha establecido una infraestructura interinstitucional que respalda la viabilidad a largo plazo de las poblaciones de animales en cautiverio. Evaluamos la habilidad de esta infraestructura coordinada de metacolecciones para apoyar en la conservación de cuatro especies de plantas curadas en colecciones vivientes en varios jardines botánicos de todo el mundo. Las limitaciones de las prácticas contemporáneas incluyen la incapacidad de recopilar, compartir y analizar los datos de las colecciones de plantas a nivel individual, así como la dificultad de rastrear la procedencia original del material ex situ. El marco de trabajo de metacolecciones coordinadas que utilizan los zoológicos puede ser adoptado por la comunidad botánica para mejorar los resultados de conservación al minimizar la pérdida de la diversidad genética que ocurre en las colecciones. Sugerimos acciones que aumenten la conservación ex situ de las especies excepcionales de plantas. Estas acciones incluyen el desarrollo de una base de datos central para acumular datos y rastrear entre las instituciones a los individuos únicos de las especies amenazadas prioritarias y la adaptación de una herramienta de manejo poblacional basada en el linaje que incorpore los aspectos únicos de la historia de vida de las plantas. Si estas acciones se plantean colaborativamente a escala regional, nacional y global, podrían transformar la conservación ex situ de las especies amenazadas de plantas.
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Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Animales , Jardinería , Plantas/genética , SemillasRESUMEN
The morphology of the early ontogenetic stages of cycad foliage may help resolve the relationships between extinct to extant cycad lineages. However, prior to this study, fossil evidence of cycad seedlings was not known. We describe a compression fossil of cycad eophylls with co-occurring fully developed leaves of adult specimens from the early Palaeocene ( ca 63.8 Ma) Castle Rock flora from the Denver Basin, CO, USA and assign it to the fossil genus Dioonopsis (Cycadales) based on leaf morphology and anatomy. The new fossil seedling foliage is particularly important because fully differentiated pinnate leaves of adult plants and the eophylls belong to the same species based on shared epidermal micromorphology, therefore, increasing the number of morphological characteristics that can be used to place Dioonopsis phylogenetically. Significantly, the seedling fossil has a basic foliage structure that is very similar to seedlings of extant cycads, which is consistent with a cycadalean affinity of Dioonopsis. Nevertheless, the set of morphological characters in the seedling and adult specimens of Dioonopsis suggests a distant relationship between Dioonopsis and extant Dioon. This indicates that extinct lineages of cycads were present and widespread during the early Cenozoic (Palaeogene) coupled with the subordinate role of extant genera in the Palaeogene fossil record of cycads.
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Cycadopsida , Fósiles , Filogenia , Hojas de la Planta , PlantonesRESUMEN
Cycads are among the few plants that have developed specialized roots to host nitrogen-fixing bacteria. We describe the bacterial diversity of the coralloid roots from seven Dioon species and their surrounding rhizosphere and soil. Using 16S rRNA gene amplicon sequencing, we found that all coralloid roots are inhabited by a broad diversity of bacterial groups, including cyanobacteria and Rhizobiales among the most abundant groups. The diversity and composition of the endophytes are similar in the six Mexican species of Dioon that we evaluated, suggesting a recent divergence of Dioon populations and/or similar plant-driven restrictions in maintaining the coralloid root microbiome. Botanical garden samples and natural populations have a similar taxonomic composition, although the beta diversity differed between these populations. The rhizosphere surrounding the coralloid root serves as a reservoir and source of mostly diazotroph and plant growth-promoting groups that colonize the coralloid endosphere. In the case of cyanobacteria, the endosphere is enriched with Nostoc spp and Calothrix spp that are closely related to previously reported symbiont genera in cycads and other early divergent plants. The data reported here provide an in-depth taxonomic characterization of the bacterial community associated with coralloid root microbiome. The functional aspects of the endophytes, their biological interactions, and their evolutionary history are the next research step in this recently discovered diversity within the cycad coralloid root microbiome.
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Bacterias Fijadoras de Nitrógeno/clasificación , Análisis de Secuencia de ADN/métodos , Zamiaceae/microbiología , Biodiversidad , ADN Ribosómico/genética , Endófitos/clasificación , Endófitos/genética , Endófitos/aislamiento & purificación , Bacterias Fijadoras de Nitrógeno/genética , Bacterias Fijadoras de Nitrógeno/aislamiento & purificación , Filogenia , Raíces de Plantas/microbiología , ARN Ribosómico 16S/genética , Rizosfera , Zamiaceae/clasificaciónRESUMEN
Recently, we found a mistake in Figure 4D in our previously published paper[...].
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Topological phase transitions constitute a new class of quantum critical phenomena. They cannot be described within the usual framework of the Landau theory since, in general, the different phases cannot be distinguished by an order parameter, neither can they be related to different symmetries. In most cases, however, one can identify a diverging length at these topological transitions. This allows us to describe them using a scaling approach and to introduce a set of critical exponents that characterize their universality class. Here we consider some relevant models of quantum topological transitions associated with well-defined critical exponents that are related by a quantum hyperscaling relation. We extend to these models a finite-size scaling approach based on techniques for calculating the Casimir force in electromagnetism. This procedure allows us to obtain universal Casimir amplitudes at their quantum critical points. Our results verify the validity of finite-size scaling in these systems and confirm the values of the critical exponents obtained previously.
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Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermo-responsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.
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Portadores de Fármacos/química , Hidrogeles/química , Células Madre Mesenquimatosas/citología , Reología , Temperatura , Cápsulas , Diferenciación Celular , Supervivencia Celular , Preparaciones de Acción Retardada , Humanos , Cinética , Ingeniería de TejidosRESUMEN
A mean-field treatment is presented of a square lattice two-orbital-model for [Formula: see text] taking into account intra- and inter-orbital superconductivity. A rich phase diagram involving both types of superconductivity is presented as a function of the ratio between the couplings of electrons in the same and different orbitals ([Formula: see text]) and electron doping x. With the help of a quantity we call orbital-mixing ratio, denoted as [Formula: see text], the phase diagram is analyzed using a simple and intuitive picture based on how [Formula: see text] varies as electron doping increases. The predictive power of [Formula: see text] suggests that it could be a useful tool in qualitatively (or even semi-quantitatively) analyzing multiband superconductivity in BCS-like superconductors.