83 results on '"Perry, Sarah"'
Search Results
2. Utilizing Artificial Intelligence-Based Deformable Registration for Global and Layer-Specific Cardiac MRI Strain Analysis in Healthy Children and Young Adults.
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Priya, Sarv, Hartigan, Tyler, Perry, Sarah S., Goetz, Sawyer, Dalla Pria, Otavio Augusto Ferreira, Walling, Abigail, Nagpal, Prashant, Ashwath, Ravi, Bi, Xiaoming, and Chitiboi, Teodora
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The absence of published reference values for multilayer-specific strain measurement using cardiac magnetic resonance (CMR) in young healthy individuals limits its use. This study aimed to establish normal global and layer-specific strain values in healthy children and young adults using a deformable registration algorithm (DRA). A retrospective study included 131 healthy children and young adults (62 males and 69 females) with a mean age of 16.6 ± 3.9 years. CMR examinations were conducted using 1.5T scanners, and strain analysis was performed using TrufiStrain research prototype software (Siemens Healthineers, Erlangen, Germany). Global and layer-specific strain parameters were extracted from balanced Steady-state free precession cine images. Statistical analyses were conducted to evaluate the impact of demographic variables on strain measurements. The peak global longitudinal strain (LS) was −16.0 ± 3.0%, peak global radial strain (RS) was 29.9 ± 6.3%, and peak global circumferential strain (CS) was −17.0 ± 1.8%. Global LS differed significantly between males and females. Transmural strain analysis showed a consistent pattern of decreasing LS and CS from endocardium to epicardium, while radial strain increased. Basal-to-apical strain distribution exhibited decreasing LS and increasing CS in both global and layer-specific analysis. This study uses DRA to provide reference values for global and layer-specific strain in healthy children and young adults. The study highlights the impact of sex and age on LS and body mass index on RS. These insights are vital for future cardiac assessments in children, particularly for early detection of heart diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Impact of a Reading Room Coordinator on Efficiency of On-Call Radiology Residents.
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Rao, Karan, Perry, Sarah, Hagedorn, Joshua, Carter, Knute, Balkenende, Brian, and Policeni, Bruno
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Few level I trauma, tertiary care, academic centers have a paid, permanent reading room coordinator (RRC) to facilitate image management services during off-hour calls, to minimize interruptions to reading workflow. The purpose of this study is to investigate the effect of an RRC on the efficiency of radiology residents signing preliminary reports for emergency department (ED) and inpatient studies. A pre- and postintervention retrospective review was performed, using carestream PACS to retrieve imaging studies read on call during two time periods—July 1 to December 1, 2019 (pre-RRC), and July 1 to December 1, 2021 (post-RRC). Efficiency of residents signing preliminary reports was measured by turnaround time (TAT), defined as the time from when a study was marked complete by a technologist to when a preliminary report was signed by a resident, in PACS. In the above time periods, residents interpreted a total of 64,406 studies on call. For ED studies, the mean TAT was 7.0 min shorter post-RRC, compared with pre-RRC (95% confidence interval [CI]: –7.8 to –6.1, (t = 15.50, degrees of freedom (df) = 31,866, P <.0001). The percentage of ED studies signed within 30 min increased from 57.7% to 65.8%, an increase of 8.1% (95% CI: 7.0% to 9.1%) after employing an RRC (χ
2 = 228.11, df = 1, P <.0001). For inpatient studies, the mean TAT was 10.2 min shorter post-RRC (95% CI: –12.3 to –8.0, t = 9.22, df = 25,193, P <.0001). An RRC increased radiology resident on-call workflow efficiency, facilitating care for patients in both the ED and inpatient setting. [Display omitted] [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Design Rules for the Sequestration of Viruses into Polypeptide Complex Coacervates.
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Joshi, Pratik U., Decker, Claire, Zeng, Xianci, Sathyavageeswaran, Arvind, Perry, Sarah L., and Heldt, Caryn L.
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- 2024
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5. Self-Assembling Polypeptides in Complex Coacervation.
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Sathyavageeswaran, Arvind, Bonesso Sabadini, Júlia, and Perry, Sarah L.
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- 2024
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6. Optimizing Deep Learning for Cardiac MRI Segmentation: The Impact of Automated Slice Range Classification.
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Priya, Sarv, Dhruba, Durjoy D., Perry, Sarah S., Aher, Pritish Y., Gupta, Amit, Nagpal, Prashant, and Jacob, Mathews
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Cardiac magnetic resonance imaging is crucial for diagnosing cardiovascular diseases, but lengthy postprocessing and manual segmentation can lead to observer bias. Deep learning (DL) has been proposed for automated cardiac segmentation; however, its effectiveness is limited by the slice range selection from base to apex. In this study, we integrated an automated slice range classification step to identify basal to apical short-axis slices before DL-based segmentation. We employed publicly available Multi-Disease, Multi-View & Multi-Center Right Ventricular Segmentation in Cardiac MRI data set with short-axis cine data from 160 training, 40 validation, and 160 testing cases. Three classification and seven segmentation DL models were studied. The top-performing segmentation model was assessed with and without the classification model. Model validation to compare automated and manual segmentation was performed using Dice score and Hausdorff distance and clinical indices (correlation score and Bland-Altman plots). The combined classification (CBAM-integrated 2D-CNN) and segmentation model (2D-UNet with dilated convolution block) demonstrated superior performance, achieving Dice scores of 0.952 for left ventricle (LV), 0.933 for right ventricle (RV), and 0.875 for myocardium, compared to the stand-alone segmentation model (0.949 for LV, 0.925 for RV, and 0.867 for myocardium). Combined classification and segmentation model showed high correlation (0.92-0.99) with manual segmentation for biventricular volumes, ejection fraction, and myocardial mass. The mean absolute difference (2.8-8.3 mL) for clinical parameters between automated and manual segmentation was within the interobserver variability range, indicating comparable performance to manual annotation. Integrating an initial automated slice range classification step into the segmentation process improves the performance of DL-based cardiac chamber segmentation. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Self-Assembling Polypeptides in Complex Coacervation
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Sathyavageeswaran, Arvind, Bonesso Sabadini, Júlia, and Perry, Sarah L.
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Intracellular compartmentalization plays a pivotal role in cellular function, with membrane-bound organelles and membrane-less biomolecular “condensates” playing key roles. These condensates, formed through liquid–liquid phase separation (LLPS), enable selective compartmentalization without the barrier of a lipid bilayer, thereby facilitating rapid formation and dissolution in response to stimuli. Intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs), which are often rich in charged and polar amino acid sequences, scaffold many condensates, often in conjunction with RNA.
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- 2024
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8. What is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee.
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Cooper, Christopher S., Lockwood, Gina M., Edwards, Angelena B., Perry, Sarah S., and Storm, Douglas W.
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The degree of chordee associated with hypospadias impacts operative management. Unfortunately, poor inter-observer reliability in assessing chordee by multiple methods in vitro has been demonstrated. This variability may be related to the fact that chordee is not a discrete angle, but rather an arc-like curvature similar to that of a banana. On an attempt to improve this variability, we assessed the inter-rater reliability of a novel method of chordee measurement and compared it to measurements with a goniometer both in vitro and in vivo. In vitro assessment of curvature was performed using 5 bananas. In vivo chordee measurement was performed during 43 hypospadias repairs. On in vitro and in vivo cases, chordee was assessed independently by faculty and resident physicians. Angle assessment was performed in a standard manner with a goniometer and with a smartphone app using ruler measurements of the length and width of the arc (Summary Figure). The proximal and distal aspect of the arc to be measured was marked on the bananas, whereas the penile measurements were taken from the penoscrotal to the sub-coronal junctions. In vitro banana assessment demonstrated strong intra- and inter-rater reliability for length (0.89 and 0.88, respectively) and width measurements (0.97 and 0.96). The calculated angle demonstrated an intra- and inter-rater reliability of 0.67 and 0.67. The banana goniometer/protractor measurements were weak with an intra-rater and inter-rater reliability of 0.33 and 0.21. With hypospadias chordee, the inter-rater reliability was strong for length and width measurements (0.95 and 0.94) and 0.48 for calculated angle. The inter-rater reliability of the goniometer angle was 0.96. Further assessment of inter-rater goniometer reliability was performed relative to degree of chordee as characterized by faculty. The inter-rater reliability for ≤15°, 16–30, and ≥30° was 0.68 (n = 20), 0.34 (n = 14), and 0.90 (n = 9), respectively. When the goniometer angle was classified as ≤15, 16–30, or ≥30° by one physician, it was classified outside of this range by the other physician 23%, 47%, and 25% of the time, respectively. Our data demonstrate significant limitations of the goniometer for assessing chordee in vitro and in vivo. We were unable to demonstrate significant improvement in chordee assessment using arc length and width measurements to calculate radians. Reliable and precise techniques for measuring hypospadias chordee remain elusive and draw into question the validity and usability of management algorithms employing discrete values. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2023
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9. Reappraisal of autologous stem cell transplantation for transformed indolent lymphoma in the bendamustine era
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Stewart, Colin, Owen, Carolyn, Shafey, Mona, Perry, Sarah, Sterrett, Russell, Peters, Anthea, Duggan, Peter, Chua, Neil, Stewart, Douglas, and Puckrin, Robert
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- 2024
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10. Surface Charge Density and Steric Repulsion in Polyelectrolyte–Surfactant Coacervation.
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Madinya, Jason J., Tjo, Hansen, Meng, Xiangxi, Ramírez Marrero, Isaac A., Sing, Charles E., and Perry, Sarah L.
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- 2023
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11. An Observational Cohort Study of the Role of Level of Effort in Post-Acute Brain Injury Rehabilitation.
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Anders, David M., Logan, Daniel M., Shelton, Jean A., Walters, G. Joseph, Perry, Sarah, Carter, Knute D., and Malec, James F.
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To investigate the role of participant level of effort (LoE) on outcome in post-acute brain injury rehabilitation with the hypothesis that greater effort is associated with more positive outcomes. Observational cohort study. Comprehensive integrated rehabilitation program for brain injury within a skilled nursing facility. Consecutive admissions with acquired brain injury (N=101). Individualized interdisciplinary brain injury rehabilitation; therapist rating of participant LoE with Acquired Brain Injury LoE Scale (ABI-LoES) during physical therapy, occupational therapy, and speech and language pathology sessions. Mayo-Portland Adaptability Inventory, fourth edition (MPAI-4); Supervision Rating Scale (SRS). Linear regression showed that discharge MPAI-4 Total T scores were significantly associated with mean ABI-LoES rating, admission MPAI-4 Total T scores, age at admission, and days from injury but not with standard deviation of ABI-LoES rating, sex, injury type, length of stay, or treatment before or during the COVID-19 pandemic. Discharge SRS scores were significantly associated with mean ABI-LoES rating, admission SRS scores, and age. A 1-unit increase in mean ABI-LoES rating was associated with 5.1-unit lower discharge MPAI-4 Total T scores and 1.5 lower discharge SRS scores, after controlling for other variables. Logistic regression showed that the odds of achieving a minimal clinically important difference on the MPAI-4 were 8.34 times higher with each 1-unit increase in mean ABI-LoES rating after controlling for other variables. Admission MPAI-4 was negatively associated with mean ABI-LoES rating (β=−0.07, t =−8.85, P <.0001). After controlling for nonmodifiable variables, average ABI-LoES rating is positively associated with outcome. Initial level of disability is negatively associated with mean ABI-LoES rating. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Surface Charge Density and Steric Repulsion in Polyelectrolyte–Surfactant Coacervation
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Madinya, Jason J., Tjo, Hansen, Meng, Xiangxi, Ramírez Marrero, Isaac A., Sing, Charles E., and Perry, Sarah L.
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Solutions of oppositely charged polyelectrolytes and surfactants can undergo phase separation, in a charge-driven process known as complex coacervation. These materials are widely used in a variety of applications because of their useful rheological and structural properties. It is understood that these properties are related to the assembly of the surfactants into micelles, which then undergo complexation with the oppositely charged polyelectrolytes to form the coacervate phase. However, there remain challenges in understanding how the molecular features of the components give rise to this useful phase behavior, with a still-nascent understanding of how electrostatics, micelle structure, composition, and steric interactions interplay to govern coacervation. In this paper, we used a combination of experiment and a recently developed hybrid simulation/theory model to understand polyelectrolyte–surfactant coacervates. We used mixtures of ionic and neutral surfactants to systematically vary the micelle surface charge density, along with PEG side-chains on the neutral surfactants to vary the steric repulsions between nearby micelles. Finally, we altered the polyelectrolyte charge density to tune the polymer-mediated attractions between micelles. By mapping the phase behavior of these solutions, we showed that higher charge density on the polymer or micelle, or decreasing steric repulsion, facilitates coacervation. We considered analogous quantities in our simulation/theory model, which makes predictions for both the thermodynamics and the structure of the micelle–polyelectrolyte rich coacervate and micelle–polyelectrolyte poor supernatant phases. By varying the micelle surface charge density and the correlation-based polymer–micelle interaction energy, we showed phase separation behaviors consistent with experiments.
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- 2023
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13. Melt Processing Pretreatment Effects on Enzymatic Depolymerization of Poly(ethylene terephthalate).
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Patel, Akanksha, Chang, Allen C., Perry, Sarah, Soong, Ya-Hue V., Ayafor, Christian, Wong, Hsi-Wu, Xie, Dongming, and Sobkowicz, Margaret J.
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- 2022
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14. ‘It’s dynamite!’: The role of popular music and the home–school connection in the special music education classroom
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Perry, Sarah
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When teaching children with disabilities, the home–school music connection can be the key to keeping our students engaged and motivated while increasing students’ self-regulation and positive interactions with peers. This article aims to shed light on classroom experiences with popular music of two third-grade students with sensory processing disorder and on how ‘music sharing turns’ influenced their overall engagement and ability to self-regulate in music classes. Music sharing turns, a weekly music ‘show and tell’, provided opportunities to bring popular music and activities they enjoy at home into the classroom. The results show that the participants were easily engaged and experienced greater self-regulation and awareness of others during music sharing turns. Music sharing turns also provided a predictable environment for peer interaction with opportunities to take on leadership roles within the classroom while remaining open-ended in a way participants could make their own.
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- 2022
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15. Linear Viscoelasticity and Time–Alcohol Superposition of Chitosan/Hyaluronic Acid Complex Coacervates.
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Sun, Juanfeng, Schiffman, Jessica D., and Perry, Sarah L.
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- 2022
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16. Receptors underlying an odorant's valence across concentrations in Drosophila larvae
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Perry, Sarah, Clark, Jonathan T., Ngo, Paulina, and Ray, Anandasankar
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Odorants interact with receptors expressed in specialized olfactory neurons, and neurons of the same class send their axons to distinct glomeruli in the brain. The stereotypic spatial glomerular activity map generates recognition and the behavioral response for the odorant. The valence of an odorant changes with concentration, typically becoming aversive at higher concentrations. Interestingly, in Drosophila larvae, the odorant (E)-2-hexenal is aversive at low concentrations and attractive at higher concentrations. We investigated the molecular and neural basis of this phenomenon, focusing on how activities of different olfactory neurons conveying opposing effects dictate behaviors. We identified the repellant neuron in the larvae as one expressing the olfactory receptor Or7a, whose activation alone at low concentrations of (E)-2-hexenal elicits an avoidance response in an Or7a-dependent manner. We demonstrate that avoidance can be overcome at higher concentrations by activation of additional neurons that are known to be attractive, most notably odorants that are known activators of Or42a and Or85c. These findings suggest that in the larval stage, the attraction-conveying neurons can overcome the aversion-conveying channels for (E)-2-hexenal.
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- 2024
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17. Effect of interventions to reduce wait times for diagnosis and treatment of sleep-disordered breathing in adults: A systematic review
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Perry, Sarah, Ronksley, Paul E., Kelly, Jenny, and Pendharkar, Sachin R.
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AbstractRATIONALE: Sleep disordered breathing (SDB) is associated with adverse health consequences that can be mitigated through timely and effective management. Guidelines provide wait time targets, but the evidence supporting them is unclear. The purpose of this systematic review was to explore the relationship between interventions to improve wait times for SDB and the effects on patient or provider outcomes.METHODS: A targeted search of medical databases was performed from database inception to June 2017. Included studies described an intervention intended to reduce wait times for the diagnosis or treatment of SDB and reported on a patient- or provider-level outcome.RESULTS: The search produced 2,944 abstracts and 51 articles underwent full text review. Ten articles were included in the final review. Five trials reported wait times to diagnosis and treatment, 3 studies described wait times for diagnosis only and 2 studies discussed time to treatment exclusively. All studies were of moderate methodological quality. Wait times were improved in most studies, but due to short follow-up periods a clear relationship with improved health outcomes was rarely established. The variety of interventions limited the characterization of specific wait-times reduction strategies that could reliably improve outcomes.CONCLUSIONS: This review highlights the scarcity of studies but suggests a possible clinical benefit of interventions to reduce wait times. However, generalizability is limited and the short follow-up periods likely underestimate potential positive impacts of reduced wait times. Further studies are needed to better characterize this relationship and to identify additional interventions to deliver more timely patient care.
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- 2022
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18. Electrospinning Fibers from Oligomeric Complex Coacervates: No Chain Entanglements Needed.
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Meng, Xiangxi, Du, Yifeng, Liu, Yalin, Coughlin, E. Bryan, Perry, Sarah L., and Schiffman, Jessica D.
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- 2021
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19. Liquid capsules for gastrointestinal drug delivery
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Liu, Jianhui, Perry, Sarah L., Tang, Ben Zhong, and Tirrell, Matthew V.
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Recently, Margossian et al. reported pH-responsive complex coacervates formed by a polyzwitterion and a polyelectrolyte in Nature Communications, which remain intact under acidic conditions (pH≤3) yet dissolve with increasing pH, suggesting the potential for oral delivery to the gastrointestinal tract.
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- 2022
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20. Electrospinning Fibers from Oligomeric Complex Coacervates: No Chain Entanglements Needed
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Meng, Xiangxi, Du, Yifeng, Liu, Yalin, Coughlin, E. Bryan, Perry, Sarah L., and Schiffman, Jessica D.
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The electrospinning field is dominated by studies that investigate parameters, such as polymer concentration and chain length, to identify conditions where the polymer chains are sufficiently entangled to facilitate fiber formation. Here, we report the first demonstration that linear, nonentangled, oligomeric polyelectrolytes can be electrospun into fibers using a traditional single-nozzle setup. Previously, we have demonstrated that the associative phase separation phenomenon known as complex coacervation facilitates the electrospinning of polyelectrolyte complex fibers directly from water. In this work, we synthesized polycations and polyanions with degrees of polymerization ranging from ∼500 down to <10, representing average molecular weights on the order of 100 to 1 kg/mol. We then quantified the phase behavior and viscosity of our various coacervate samples as a function of both chain length and salt concentration. Our results confirm that the polymer concentration in all samples was near or above the estimated value for the overlap concentration and that only the longest polymer samples were expected to experience entanglements. However, we were able to electrospin fibers from all of our coacervate samples, even oligomers. Thus, the electrospinnability of coacervates is fundamentally different from the traditional electrospinning of linear, neutral polymers or solutions composed of polyelectrolytes mixed with neutral polymers. In the same way that coacervation represents a novel way to enable the electrospinning of polyelectrolytes from water, the associative interactions driving phase separation eliminate the need for entanglements by slowing the timescale for relaxation. Our results suggest an alternative route that enables the electrospinning of novel solutions by decoupling chain-length requirements from other length-dependent parameters.
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- 2021
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21. Synthesis and quality assessment of in vitroRNA-novel synthesis and analytical approaches
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Vaishnav, Jamuna, Banerjee, Ruptanu, Mala, Purnima, Palaniswamy, Diwakaran Rathinam, Martin, Craig T., and Perry, Sarah
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- 2024
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22. Procedural Interventions for Terminally Ill Children – Are We Aiding Palliation?
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Phillips, Hannah, Perry, Sarah, Shinkunas, Laura A, and Carlisle, Erica M
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Objectives:Many children undergo surgery or an invasive procedure during their terminal hospital admission.1The types of procedures, patients, and the intent of the procedures has not been well defined. Understanding these details may help pediatric surgeons better determine the clinical settings in which certain procedures will not enhance palliation or survival. Methods:A retrospective single institution chart review was performed for patients age 14 days to 18 years with chronic conditions who died while inpatient from 2013–2017. Data was gathered on demographics, primary diagnosis, intubation status, palliative care involvement, duration of hospital stay, length of palliative care involvement, and total number of procedures. Negative binomial regression was used to assess association with number of procedures. Results:132 children met inclusion criteria. Most children were White and less than one year old. The most common type of diagnosis was cardiac in nature. Children underwent an average of three procedures. 75% were intubated and 77.5% had palliative care involved. Patients who were less than one year old at death were more likely to have been intubated, had longer terminal hospital stays, and had more procedures. Those who were intubated underwent more procedures and had longer hospital stays. Those with longer palliative care involvement had fewer procedures. Conclusions:Children undergo a significant number of surgical procedures during their terminal hospitalization. This may be influenced by age, intubation status, and length of stay. Ongoing study may help refine which procedures may have limited impact on survival in the chronically ill pediatric population.
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- 2024
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23. Decoupling the Effects of Charge Density and Hydrophobicity on the Phase Behavior and Viscoelasticity of Complex Coacervates
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Ramírez Marrero, Isaac A., Boudreau, Luke, Hu, Weiguo, Gutzler, Rainer, Kaiser, Nadine, von Vacano, Bernhard, Konradi, Rupert, and Perry, Sarah L.
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Here, we explore the effect of copolymer chemistry on the phase behavior and viscoelasticity of complex coacervates. To this end, we utilized a library of methacrylate copolymers with varying charge densities and hydrophobicity. Our results show that changing the charge density and hydrophobicity drastically affects the phase behavior─with charge density dictating the salt stability and hydrophobicity controlling the polymer concentration of the coacervates. Small-amplitude oscillatory shear measurements were used to study the viscoelastic response of the coacervates, leveraging knowledge of the coacervate phase behavior in tandem with time-salt superposition to construct a series of time-salt-copolymer master curves that highlight the effects of polymer charge density and hydrophobicity. These combined data show evidence of charge-dominated and hydrophobicity-dominated regimes, allowing for an understanding of how copolymer chemistry can be used to tune the mechanical properties of complex coacervates.
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- 2024
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24. Effect of Polymer Chemistry on the Linear Viscoelasticity of Complex Coacervates.
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Liu, Yalin, Santa Chalarca, Cristiam F., Carmean, R. Nicholas, Olson, Rebecca A., Madinya, Jason, Sumerlin, Brent S., Sing, Charles E., Emrick, Todd, and Perry, Sarah L.
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- 2020
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25. Electrospinning Nanofibers from Chitosan/Hyaluronic Acid Complex Coacervates.
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Sun, Juanfeng, Perry, Sarah L., and Schiffman, Jessica D.
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- 2019
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26. A survey of quality measurement in Canadian sleep centers
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Liang, Alicia, Santana, Maria J., Perry, Sarah, and Pendharkar, Sachin R.
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AbstractRATIONALE: Quality indicators have been published for the management of sleep-disordered breathing, but the extent to which quality of care is measured by Canadian sleep centers is unknown.OBJECTIVEThe objective of this study is to characterize the measurement of healthcare quality as reported by Canadian sleep centers.METHODSWe performed a national online survey of Canadian sleep centers. Surveys were distributed by Canadian respiratory and sleep specialty societies. Respondents reporting formal quality measurement were contacted to complete telephone interviews that characterized the process through which quality was assessed. Questions explored the indicators used, the process by which quality data was collected and reported and barriers and facilitators to effective quality measurement. Quality indicators were categorized based on the aspect of clinical care being evaluated and classified using the Institute of Medicine’s (IOM) quality dimensions (safe, effective, patient-centered, timely, efficient, equitable) and Donabedian’s structure-process-outcome framework.MEASUREMENTS AND MAIN RESULTS: Thirty-four survey responses were received, of which 20 sleep centers reported formal quality measurement. Interviews with 19 of these centers identified 61 indicators that were classified into 11 unique categories. The IOM dimensions of patient-centeredness, effectiveness and timeliness were most common while no centers evaluated equity and only one center measured efficiency. All centers used process measures, while most used outcome measures and only one used a structural quality measure.CONCLUSIONSAmong Canadian sleep centers that report formally assessing healthcare quality, measurement was highly variable. These findings highlight the need to identify and mitigate barriers to quality measurement to improve sleep-disordered breathing care.
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- 2021
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27. Effect of Polymer Chemistry on the Linear Viscoelasticity of Complex Coacervates
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Liu, Yalin, Santa Chalarca, Cristiam F., Carmean, R. Nicholas, Olson, Rebecca A., Madinya, Jason, Sumerlin, Brent S., Sing, Charles E., Emrick, Todd, and Perry, Sarah L.
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Complex coacervates can form through the electrostatic complexation of oppositely charged polymers. The material properties of the resulting coacervates can change based on the polymer chemistry and the complex interplay between electrostatic interactions and water structure, controlled by salt. We examined the effect of varying the polymer backbone chemistry using methacryloyl- and acryloyl-based complex coacervates over a range of polymer chain lengths and salt conditions. We simultaneously quantified the coacervate phase behavior and the linear viscoelasticity of the resulting coacervates to understand the interplay between polymer chain length, backbone chemistry, polymer concentration, and salt concentration. Time-salt superposition analysis was used to facilitate a broader characterization and comparison of the stress relaxation behavior between different coacervate samples. Samples with mismatched polymer chain lengths highlighted the ways in which the shortest polymer chain can dominate the resulting coacervate properties. A comparison between coacervates formed from methacryloyl vs acryloyl polymers demonstrated that the presence of a backbone methyl group affects the phase behavior, and thus the rheology in such a way that coacervates formed from methacryloyl polymers have a similar phase behavior to those of acryloyl polymers with ∼10× longer polymer chains.
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- 2020
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28. Thermostabilization of viruses viacomplex coacervationElectronic supplementary information (ESI) available: Physical characterization of polymers, sample recipes, virus recovery data, raw virus titer data from thermal stability experiments, and cytotoxicity data. See DOI: 10.1039/d0bm01433h
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Mi, Xue, Blocher McTigue, Whitney C., Joshi, Pratik U., Bunker, Mallory K., Heldt, Caryn L., and Perry, Sarah L.
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Widespread vaccine coverage for viral diseases could save the lives of millions of people each year. For viral vaccines to be effective, they must be transported and stored in a narrow temperature range of 2–8 °C. If temperatures are not maintained, the vaccine may lose its potency and would no longer be effective in fighting disease; this is called the cold storage problem. Finding a way to thermally stabilize a virus and end the need to transport and store vaccines at refrigeration temperatures will increase access to life-saving vaccines. We explore the use of polymer-rich complex coacervates to stabilize viruses. We have developed a method of encapsulating virus particles in liquid complex coacervates that relies on the electrostatic interaction of viruses with polypeptides. In particular, we tested the incorporation of two model viruses; a non-enveloped porcine parvovirus (PPV) and an enveloped bovine viral diarrhea virus (BVDV) into coacervates formed from poly(lysine) and poly(glutamate). We identified optimal conditions (i.e., the relative amount of the two polypeptides) for virus encapsulation, and trends in this composition matched differences in the isoelectric point of the two viruses. Furthermore, we were able to achieve a ∼103–104-fold concentration of virus into the coacervate phase, such that the level of virus remaining in the bulk solution approached our limit of detection. Lastly, we demonstrated a significant enhancement of the stability of non-enveloped PPV during an accelerated aging study at 60 °C over the course of a week. Our results suggest the potential for using coacervation to aid in the purification and formulation of both enveloped and non-enveloped viruses, and that coacervate-based formulations could help limit the need for cold storage throughout the transportation and storage of vaccines based on non-enveloped viruses.
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- 2020
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29. Electrospinning Nanofibers from Chitosan/Hyaluronic Acid Complex Coacervates
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Sun, Juanfeng, Perry, Sarah L., and Schiffman, Jessica D.
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Electrospun biopolyelectrolyte nanofibers hold potential for use in a range of biomedical applications, but eliminating toxic chemicals involved in their production remains a key challenge. In this study, we successfully electrospun nanofibers from an aqueous complex coacervate solution composed of chitosan and hyaluronic acid. Experimentally, we investigated the effect of added salt and electrospinning apparatus parameters, such as how applied voltage affected fiber formation. We also studied how the addition of alcohol cosolvents affected the properties of the coacervate solution and the resulting nanofibers. Overall, we observed a trade-off in how the addition of salt and alcohol affected the phase behavior and rheology of the coacervates and, consequently, the size of the resulting fibers. While salt served to weaken electrostatic associations within the coacervate and decrease the precursor solution viscosity, the addition of alcohol lowered the dielectric constant of the system and strengthened these interactions. We hypothesize that the optimized concentration of alcohol accelerated the solvent evaporation during the electrospinning process to yield desirable nanofiber morphology. The smallest average nanofiber diameter was determined to be 115 ± 30 nm when coacervate samples were electrospun using an aqueous solvent containing 3 wt % ethanol and an applied voltage of 24 kV. These results demonstrate a potentially scalable strategy to manufacture electrospun nanofibers from biopolymer complex coacervates that eliminate the need for toxic solvents and could enable the use of these materials across a range of biomedical applications.
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- 2019
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30. Bacteria-Resistant, Transparent, Free-Standing Films Prepared from Complex Coacervates.
- Author
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Kurtz, Irene S., Sui, Shuo, Hao, Xi, Huang, Mengfei, Perry, Sarah L., and Schiffman, Jessica D.
- Published
- 2019
- Full Text
- View/download PDF
31. Designing Electrostatic Interactions via Polyelectrolyte Monomer Sequence.
- Author
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Lytle, Tyler K., Chang, Li-Wei, Markiewicz, Natalia, Perry, Sarah L., and Sing, Charles E.
- Published
- 2019
- Full Text
- View/download PDF
32. Electrospinning Cargo-Containing Polyelectrolyte Complex Fibers: Correlating Molecular Interactions to Complex Coacervate Phase Behavior and Fiber Formation.
- Author
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Meng, Xiangxi, Schiffman, Jessica D., and Perry, Sarah L.
- Published
- 2018
- Full Text
- View/download PDF
33. Improving the Utilization and Tolerability of Thiotepa-Based Autologous Stem Cell Transplantation in Primary CNS Lymphoma
- Author
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Puckrin, Robert, Stewart, Colin, Owen, Carolyn, Street, Lesley E., Perry, Sarah, Duggan, Peter, Shafey, Mona, Chua, Neil, and Stewart, Douglas A.
- Abstract
Background:Thiotepa-based autologous stem cell transplantation (ASCT) improves survival in primary central nervous system lymphoma (PCNSL) but up to 30-60% of patients are unable to receive ASCT after MATRix induction, frequently due to treatment-related adverse events. Common conditioning regimens such as thiotepa/BCNU or thiotepa/busulfan/cyclophosphamide have also been associated with risks of pulmonary toxicity or increased transplant-related mortality. Novel strategies to improve the utilization and tolerability of ASCT are therefore needed to maximize the curative potential of this therapy in PCNSL.
- Published
- 2023
- Full Text
- View/download PDF
34. Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer.
- Author
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Khot, M. Ibrahim, Perry, Sarah L., Maisey, Thomas, Armstrong, Gemma, Andrew, Helen, Hughes, Thomas A., Kapur, Nikil, and Jayne, David G.
- Abstract
Highlights • 3D spheroids are more resistant to Hypericin-PDT than 2D cell models. • ABCG2 is upregulated in 3D spheroids as compared to 2D cell models. • Inhibiting ABCG2 could potentially improve response to Hypericin-PDT. Abstract Background Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids. Methods Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm
2 ) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated. Results Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01). Conclusions Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
35. Synthesis of Zwitterionic Pluronic Analogs.
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Skinner, Matthew, Johnston, Brandon M., Liu, Yalin, Hammer, Brenton, Selhorst, Ryan, Xenidou, Ioanna, Perry, Sarah L., and Emrick, Todd
- Published
- 2018
- Full Text
- View/download PDF
36. Three-dimensional imaging control of osteogenesis induced by minimally invasive corticotomies: Perspectives from a case report
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Ancel, Hugo, Roisin, Louis-Charles, Dufau-Perry, Sarah, and Charrier, Jean-Baptiste
- Abstract
Corticotomies are now an integral part of the orthodontist's therapeutic arsenal in adult orthodontics. In recent years, the number of publications about different surgical techniques has increased significantly. This shows that practitioners and patients have a common interest. It is now accepted that corticotomies cause a regional acceleratory phenomenon, which enables a faster dental movement, a reduction in treatment time, as well as a reduction in the risk of root resorption. The perspective of osteogenesis induced by corticotomies has already been mentioned in literature. It could provide a real advantage in maintaining the periodontium, reducing the risk of fenestration or dehiscence and the stability of long-term treatment by increasing the dental bone envelope. Through a clinical case, treated by mini- invasive surgical technique (as described in the previous article), we highlight the potential for osteogenesis induced by alveolar corticotomies and the utility of this procedure in adults.
- Published
- 2019
- Full Text
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37. Designing Electrostatic Interactions via Polyelectrolyte Monomer Sequence
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Lytle, Tyler K., Chang, Li-Wei, Markiewicz, Natalia, Perry, Sarah L., and Sing, Charles E.
- Abstract
Charged polymers are ubiquitous in biological systems because electrostatic interactions can drive complicated structure formation and respond to environmental parameters such as ionic strength and pH. In these systems, function emerges from sophisticated molecular design; for example, intrinsically disordered proteins leverage specific sequences of monomeric charges to control the formation and function of intracellular compartments known as membraneless organelles. The role of a charged monomer sequence in dictating the strength of electrostatic interactions remains poorly understood despite extensive evidence that sequence is a powerful tool biology uses to tune soft materials. In this article, we use a combination of theory, experiment, and simulation to establish the physical principles governing sequence-driven control of electrostatic interactions. We predict how arbitrary sequences of charge give rise to drastic changes in electrostatic interactions and correspondingly phase behavior. We generalize a transfer matrix formalism that describes a phase separation phenomenon known as “complex coacervation” and provide a theoretical framework to predict the phase behavior of charge sequences. This work thus provides insights into both how charge sequence is used in biology and how it could be used to engineer properties of synthetic polymer systems.
- Published
- 2019
- Full Text
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38. Electrospinning Cargo-Containing Polyelectrolyte Complex Fibers: Correlating Molecular Interactions to Complex Coacervate Phase Behavior and Fiber Formation
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Meng, Xiangxi, Schiffman, Jessica D., and Perry, Sarah L.
- Abstract
We present the first demonstration of the direct encapsulation of cargo into polyelectrolyte complex (PEC) fiber mats. This approach takes advantage of the intrinsic self-assembly characteristics of complex coacervates to simplify the formulation requirements to electrospin fibers containing a high loading and an even distribution of cargo. Two families of structurally similar fluorescent dyes were used as model cargo of varying hydrophobicity and charge and were encapsulated into coacervates of poly(4-styrenesulfonic acid, sodium salt) and poly(diallyldimethylammonium chloride). The coacervate phase behavior, dye partitioning, and resulting fibers were systematically investigated as a function of dye and salt concentration. Strong partitioning was facilitated by favorable electrostatic and π–π interactions but was adversely affected by increased salt. We further identified that dye and salt interactions can be treated as independent control parameters to modulate the properties and electrospinnability of the coacervate precursor solutions. These findings facilitate the use of electrospun PEC fibers in applications related to biomedicine, energy, and separations where cargo-loaded mats are needed.
- Published
- 2018
- Full Text
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39. Molecular Connectivity and Correlation Effects on Polymer Coacervation.
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Radhakrishna, Mithun, Basu, Kush, Liu, Yalin, Shamsi, Rasmia, Perry, Sarah L., and Sing, Charles E.
- Published
- 2017
- Full Text
- View/download PDF
40. A STUDENT-CREATED, OPEN ACCESS, LIVING TEXTBOOK.
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GALARZA, SUALYNETH, PERRY, SARAH L., and PEYTON, SHELLY R.
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CHEMICAL engineering education ,CURRICULUM ,ENGINEERING students ,GRADING of students ,HIGHER education - Published
- 2017
41. The pandemic letters.
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Perry, Sarah and Guglani, Sam
- Abstract
The Critics: Arts From the beginning of the pandemic, unable to write the novel I had been working on, and at a loss to comprehend the scale and speed of the changes brought by coronavirus, I spoke often with my friend Dr Sam Guglani, an NHS consultant oncologist based in Cheltenham - where he manages patients with lung and brain tumours - and a novelist and writer for the Lancet. SP This idea that the response to the pandemic has privileged the privileged - and the statistics around the disproportionate deaths of BAME people have made this unignorable - is so vital, and, yes: it damages our shared humanity, absolutely. SP I have begun to see the virus as a kind of magnifying lens. [Extracted from the article]
- Published
- 2020
42. Synthesis of Zwitterionic Pluronic Analogs
- Author
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Skinner, Matthew, Johnston, Brandon M., Liu, Yalin, Hammer, Brenton, Selhorst, Ryan, Xenidou, Ioanna, Perry, Sarah L., and Emrick, Todd
- Abstract
Novel polymer amphiphiles with chemical structures designed as zwitterionic analogs of Pluronic block copolymers were prepared by controlled free radical polymerization of phosphorylcholine (PC) or choline phosphate (CP) methacrylate monomers from a difunctional poly(propylene oxide) (PPO) macroinitiator. Well-defined, water-dispersible zwitterionic triblock copolymers, or “zwitteronics”, were prepared with PC content ranging from 5 to 47 mol percent and composition-independent surfactant characteristics in water, which deviate from the properties of conventional Pluronic amphiphiles. These PC-zwitteronics assembled into nanoparticles in water, with tunable sizes and critical aggregation concentrations (CACs) based on their hydrophilic–lipophilic balance (HLB). Owing to the lower critical solution temperature (LCST) miscibility of the hydrophobic PPO block in water, PC-zwitteronics exhibited thermoreversible aqueous solubility tuned by block copolymer composition. The chemical versatility of this approach was demonstrated by embedding functionality, in the form of alkyne groups, directly into the zwitterion moieties. These alkynes proved ideal for cross-linking the zwitteronic nanoparticles and for generating nanoparticle-cross-linked hydrogels using UV-initiated thiol–yne “click” chemistry.
- Published
- 2018
- Full Text
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43. Sprouts and Parsnip Wine.
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PERRY, SARAH
- Subjects
- BLUE Field, The (Short story), MOORE, John
- Published
- 2018
44. Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates
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McCall, Patrick M., Srivastava, Samanvaya, Perry, Sarah L., Kovar, David R., Gardel, Margaret L., and Tirrell, Matthew V.
- Abstract
Biomolecules exist and function in cellular microenvironments that control their spatial organization, local concentration, and biochemical reactivity. Due to the complexity of native cytoplasm, the development of artificial bioreactors and cellular mimics to compartmentalize, concentrate, and control the local physico-chemical properties is of great interest. Here, we employ self-assembling polypeptide coacervates to explore the partitioning of the ubiquitous cytoskeletal protein actin into liquid polymer-rich droplets. We find that actin spontaneously partitions into coacervate droplets and is enriched by up to ∼30-fold. Actin polymerizes into micrometer-long filaments and, in contrast to the globular protein BSA, these filaments localize predominately to the droplet periphery. We observe up to a 50-fold enhancement in the actin filament assembly rate inside coacervate droplets, consistent with the enrichment of actin within the coacervate phase. Together these results suggest that coacervates can serve as a versatile platform in which to localize and enrich biomolecules to study their reactivity in physiological environments.
- Published
- 2018
- Full Text
- View/download PDF
45. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota
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Watson, Henry, Mitra, Suparna, Croden, Fiona C, Taylor, Morag, Wood, Henry M, Perry, Sarah L, Spencer, Jade A, Quirke, Phil, Toogood, Giles J, Lawton, Clare L, Dye, Louise, Loadman, Paul M, and Hull, Mark A
- Abstract
ObjectiveOmega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22).DesignA randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry.ResultsBoth omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburiaand Lactobacilluswas observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects.ConclusionOmega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure.Trial registration numberISRCTN18662143.
- Published
- 2018
- Full Text
- View/download PDF
46. Future Changes to El Niño–Southern Oscillation Temperature and Precipitation Teleconnections
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Perry, Sarah J., McGregor, Shayne, Gupta, Alex Sen, and England, Matthew H.
- Abstract
Potential changes to the El Niño–Southern Oscillation (ENSO) resulting from climate change may have far reaching impacts through atmospheric teleconnections. Here ENSO temperature and precipitation teleconnections between the historical and high‐emission future simulations are compared in 40 models from phase 5 of the Coupled Model Intercomparison Project. Focusing on the global land area only, we show that there are robust increases in the spatial extent of ENSO teleconnections during austral summer in 2040–2089 of ~19% for temperature and ~12% for precipitation in the multimodel mean (MMM), relative to the 1950–1999 period. The MMM further shows that the expansion of ENSO teleconnection extent is at least partly related to a strengthening of ENSO teleconnections over continental regions; however, a consistent strengthening is not found across the individual models. This suggests that while more land may be affected by ENSO, the existing teleconnections may not be simply strengthened. The majority of CMIP5 models project robust increases in the spatial extent of ENSO temperature and precipitation teleconnections over landThe increase in area is related to the amplified ENSO‐driven precipitation across the equatorial Pacific in the futureDespite the robust increase in area over land, we do not find a consistent strengthening of these teleconnections in the individual models
- Published
- 2017
- Full Text
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47. The Role of Histone Deacetylase 6 in Synaptic Plasticity and Memory
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Perry, Sarah, Kiragasi, Beril, Dickman, Dion, and Ray, Anandasankar
- Abstract
Histone deacetylases (HDACs) have been extensively studied as drug targets in neurodegenerative diseases, but less is known about their role in healthy neurons. We tested zinc-dependent HDACs using RNAi in Drosophila melanogasterand found memory deficits with RPD3and HDAC6. We demonstrate that HDAC6 is required in both the larval and adult stages for normal olfactory memory retention. Neuronal expression of HDAC6rescued memory deficits, and we demonstrate that the N-terminal deacetylase (DAC) domain is required for this ability. This suggests that deacetylation of synaptic targets associated with the first DAC domain, such as the active-zone scaffold Bruchpilot, is required for memory retention. Finally, electrophysiological experiments at the neuromuscular junction reveal that HDAC6mutants exhibit a partial block of homeostatic plasticity, suggesting that HDAC6 may be required for the stabilization of synaptic strength. The learning deficit we observe in HDAC6mutants could be a behavioral consequence of these synaptic defects.
- Published
- 2017
- Full Text
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48. Mechanosensory hair cells express two molecularly distinct mechanotransduction channels
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Wu, Zizhen, Grillet, Nicolas, Zhao, Bo, Cunningham, Christopher, Harkins-Perry, Sarah, Coste, Bertrand, Ranade, Sanjeev, Zebarjadi, Navid, Beurg, Maryline, Fettiplace, Robert, Patapoutian, Ardem, and Müller, Ulrich
- Abstract
Auditory hair cells contain mechanotransduction channels that rapidly open in response to sound-induced vibrations. We report here that auditory hair cells contain two molecularly distinct mechanotransduction channels. One ion channel is activated by sound and is responsible for sensory transduction. This sensory transduction channel is expressed in hair cell stereocilia, and previous studies show that its activity is affected by mutations in the genes encoding the transmembrane proteins TMHS, TMIE, TMC1 and TMC2. We show here that the second ion channel is expressed at the apical surface of hair cells and that it contains the Piezo2 protein. The activity of the Piezo2-dependent channel is controlled by the intracellular Ca2+concentration and can be recorded following disruption of the sensory transduction machinery or more generally by disruption of the sensory epithelium. We thus conclude that hair cells express two molecularly and functionally distinct mechanotransduction channels with different subcellular distributions.
- Published
- 2017
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49. Design Rules for the Sequestration of Viruses into Polypeptide Complex Coacervates
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Joshi, Pratik U., Decker, Claire, Zeng, Xianci, Sathyavageeswaran, Arvind, Perry, Sarah L., and Heldt, Caryn L.
- Abstract
Encapsulation is a strategy that has been used to facilitate the delivery and increase the stability of proteins and viruses. Here, we investigate the encapsulation of viruses via complex coacervation, which is a liquid–liquid phase separation resulting from the complexation of oppositely charged polymers. In particular, we utilized polypeptide-based coacervates and explored the effects of peptide chemistry, chain length, charge patterning, and hydrophobicity to better understand the effects of the coacervating polypeptides on virus incorporation. Our study utilized two nonenveloped viruses, porcine parvovirus (PPV) and human rhinovirus (HRV). PPV has a higher charge density than HRV, and they both appear to be relatively hydrophobic. These viruses were compared to characterize how the charge, hydrophobicity, and patterning of chemistry on the surface of the virus capsid affects encapsulation. Consistent with the electrostatic nature of complex coacervation, our results suggest that electrostatic effects associated with the net charge of both the virus and polypeptide dominated the potential for incorporating the virus into a coacervate, with clustering of charges also playing a significant role. Additionally, the hydrophobicity of a virus appears to determine the degree to which increasing the hydrophobicity of the coacervating peptides can enhance virus uptake. Nonintuitive trends in uptake were observed with regard to both charge patterning and polypeptide chain length, with these parameters having a significant effect on the range of coacervate compositions over which virus incorporation was observed. These results provide insights into biophysical mechanisms, where sequence effects can control the uptake of proteins or viruses into biological condensates and provide insights for use in formulation strategies.
- Published
- 2023
- Full Text
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50. Excess glutamate release triggers subunit-specific homeostatic receptor scaling
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Han, Yifu, Goel, Pragya, Chen, Jiawen, Perry, Sarah, Tran, Nancy, Nishimura, Samantha, Sanjani, Manisha, Chien, Chun, and Dickman, Dion
- Abstract
Ionotropic glutamate receptors (GluRs) are targets for modulation in Hebbian and homeostatic synaptic plasticity and are remodeled by development, experience, and disease. We have probed the impact of synaptic glutamate levels on the two postsynaptic GluR subtypes at the Drosophilaneuromuscular junction, GluRA and GluRB. We first demonstrate that GluRA and GluRB compete to establish postsynaptic receptive fields, and that proper GluR abundance and composition can be orchestrated in the absence of any synaptic glutamate release. However, excess glutamate adaptively tunes postsynaptic GluR abundance, echoing GluR scaling observed in mammalian systems. Furthermore, when GluRA vs. GluRB competition is eliminated, GluRB becomes insensitive to glutamate modulation. In contrast, GluRA is now homeostatically regulated by excess glutamate to maintain stable miniature activity, where Ca2+permeability through GluRA receptors is required. Thus, excess glutamate, GluR competition, and Ca2+signaling collaborate to selectively target GluR subtypes for homeostatic regulation at postsynaptic compartments.
- Published
- 2023
- Full Text
- View/download PDF
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