Chain exchange between block polymer micelles in highly selective solvents, such as water, is well-known to be arrested under quiescent conditions, yet this work demonstrates that simple agitation ...methods can induce rapid chain exchange in these solvents. Aqueous solutions containing either pure poly(butadiene-b-ethylene oxide) or pure poly(butadiene-b-ethylene oxide-d 4) micelles were combined and then subjected to agitation by vortex mixing, concentric cylinder Couette flow, or nitrogen gas sparging. Subsequently, the extent of chain exchange between micelles was quantified using small angle neutron scattering. Rapid vortex mixing induced chain exchange within minutes, as evidenced by a monotonic decrease in scattered intensity, whereas Couette flow and sparging did not lead to measurable chain exchange over the examined time scale of hours. The linear kinetics with respect to agitation time suggested a surface-limited exchange process at the air–water interface. These findings demonstrate the strong influence of processing conditions on block polymer solution assemblies.
Natural killer (NK) cells are innate immune lymphocytes that are critical for normal host defense against infections and mediate antitumor immune responses. MicroRNAs (miRNAs) are a family of small, ...noncoding RNAs that posttranscriptionally regulate the majority of cellular processes and pathways. Our understanding of how miRNAs regulate NK cells biology is limited, but recent studies have provided novel insight into their expression by NK cells, and how they contribute to the regulation of NK cell development, maturation, survival, and effector function. Here, we review the expression of miRNAs by NK cells, their contribution to cell intrinsic and extrinsic control of NK cell development and effector response, and their dysregulation in NK cell malignancies.
We present our efforts to scale up proton-conducting ceramic fuel cells (PCFCs) from the button-cell level into small, multi-cell stacks. While recent advancements with lab-scale PCFCs are ...encouraging, there are few reports of scaling PCFC technology to the stack level. The compatibility of protonic-ceramic materials with stack-packaging materials - metallic interconnects, current collectors, glass-ceramic sealants, gaskets - has not been demonstrated. Here we show that through tuning of materials, fabrication procedures, and operating conditions, protonic-ceramic fuel cell stacks can achieve reasonable performance and low degradation.
The MEA is based around barium cerate-zirconate perovskites. Better long-term stack durability is found with BaCe0.4Zr0.4Y0.1Yb0.1O3−δ (BCZYYb) electrolyte. The anode support is a nickel-electrolyte composite, while the cathode is BaCo0.4Fe0.4Zr0.1Y0.1O3−δ (BCFZY). Planar MEAs reach 5 cm2 in active area, and are packaged within ferritic-steel interconnects and macor frames to form multi-cell stacks. Our three-cell stack demonstrates encouraging performance, reaching 0.69 and 0.47 W cm−2 under H2 and CH4 fuels, respectively, at 600 ∘C. A gadolinium-doped ceria cathode-electrolyte interlayer reduces degradation rates to 1.5% kh−1 at 0.1 A cm−2 and 3.3% kh−1 at 0.4 A cm−2 at 550 ∘C. No chromium transport is observed. Degradation mechanisms and the role of the GDC interlayer are postulated.
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•Proton-conducting ceramic fuel cells scaled up from button-cells to small-stacks.•Materials set includes BaCe0.4Zr0.4Y0.1Yb0.1O3-d electrolyte.•Stack power density reaches 0.69 and 0.47 W cm−2 under H2 and CH4 fuels at 600 °C.•10% gadolinium-doped ceria interlayer proves critical to reducing stack degradation.•Materials and fabrication tuned to reduce degradation to 1.5% kh−1 at 550 °C.
Digital pill systems (DPSs), which comprise ingestible radiofrequency sensors integrated into a gelatin capsule that overencapsulates a medication, can directly measure ingestion events.
Teaching ...users to operate a DPS is vital to ensure the collection of actionable ingestion and adherence data. In this study, we aim to develop and pilot a training program, grounded in the Technology Acceptance Model, to instruct individuals on DPS operation.
A two-part training program, comprising in-person and text message-based components, was used with HIV-negative men who have sex with men with nonalcohol substance use, who had enrolled in a 90-day pilot demonstration study using the DPS to measure adherence to pre-exposure prophylaxis. We assessed the number of responses to text check-ins, the number and types of episodes where technical support was requested, the resolutions of such issues, and engagement with the program over the study period. Participant feedback on the program was evaluated through qualitative user experience interviews.
A total of 15 participants were enrolled in and completed the program. Seven technical challenges related to DPS operations were reported across 5 participants. Most commonly, participants requested support connecting the wearable Reader device with their smartphone, charging the Reader, and operating the mobile app. A total of 6 issues were resolved asynchronously or in real time via phone; 1 required in-person evaluation and resolution. Preliminary qualitative findings indicate that both the in-person and remote follow-up components of the training program were perceived as acceptable. Suggested improvements included repeated DPS refresher sessions at in-person follow-up visits and enhanced written materials for the independent resolution of technological issues.
A brief two-part DPS training program, drawing from individuals' experiences and from the Technology Acceptance Model, can provide valuable insights for users. The program also identifies and addresses several areas of actual or potential challenges related to operating a DPS and allows for the resolution of such issues within the first week of DPS use.
The Mitchell's satyr,
, is an endangered species that is limited to highly isolated habitats in the northern and southern United States. Conservation strategies for isolated endangered species often ...implement captive breeding and translocation programs for repopulation. However, these programs risk increasing the spread of harmful pathogens, such as the bacterial endosymbiont
.
can manipulate the host's reproduction leading to incompatibilities between infected and uninfected hosts. This study uses molecular methods to screen for
presence across the distribution of the Mitchell's satyr and its subspecies, St. Francis satyr, which are both federally listed as endangered and are considered two of the rarest butterflies in North America. The screens confirmed the presence of
in the northern and newly discovered southern populations of the Mitchell's satyr, but not in the St. Francis satyr population. These results combined with previous reports of
in
highlight that
infection varies both geographically and temporally in satyr populations. The temporal variance shows the importance of continued monitoring of
infection during conservation programs. To reduce the risk of reproductive incompatibilities, it is advised that all individuals collected for conservation purposes be screened for
and recommended to avoid the use of infected individuals for captive breeding and translocation programs.
Candida albicans causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide ...toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in C. albicans strain SC5314, but recent investigations have revealed candidalysin “variants” of differing amino acid sequence in isolates of C. albicans, and the related species C. dubliniensis, and C tropicalis, suggesting that sequence variation among candidalysins may be widespread in natural populations of these Candida species. Here, we analyzed ECE1 gene sequences from 182 C. albicans isolates, 10 C. dubliniensis isolates, and 78 C. tropicalis isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant Candida species.IMPORTANCEFungal infections are a significant burden to health. Candidalysin is a toxin produced by Candida albicans that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species C. dubliniensis and C. tropicalis, thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin “variant” toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of C. albicans, C. dubliniensis, and C. tropicalis and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity.
In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the ...first three years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research.
ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the peri-operative microsystem. The components were developed from available evidence, a detailed needs assessment of the hospitals, reviewing experiences from prior surgical and non-surgical QI Collaboratives, and interviews with QI experts. The components comprise 5 domains: guided implementation (e.g., mentors, coaches, statewide QI projects), education (e.g., process improvement (PI) curriculum), hospital- and surgeon-level comparative performance reports (e.g., process, outcomes, costs), networking (e.g., forums to share QI experiences and best practices), and funding (e.g., for the overall program, pilot grants, and bonus payments for improvement).
Through implementation of the 21 novel ISQIC components, hospitals were equipped to use their data to successfully implement QI initiatives and improve care. Formal (QI/PI) training, mentoring, and coaching were undertaken by the hospitals as they worked to implement solutions. Hospitals received funding for the program and were able to work together on statewide quality initiatives. Lessons learned at one hospital were shared with all participating hospitals through conferences, webinars, and toolkits to facilitate learning from each other with a common goal of making care better and safer for the surgical patient in Illinois. Over the first three years, surgical outcomes improved in Illinois.
The first three years of ISQIC improved care for surgical patients across Illinois and allowed hospitals to see the value of participating in a surgical QI learning collaborative without having to make the initial financial investment themselves. Given the strong support and buy-in from the hospitals, ISQIC has continued beyond the initial three years and continues to support QI across Illinois hospitals.
Recent studies suggest that the cyclin-dependent kinase (CDK) pathway may be a therapeutic target for brain metastases (BM). Here, we present interim analysis of a basket trial evaluating the ...intracranial efficacy of the CDK inhibitor palbociclib in patients with progressive BM and CDK alterations. Our study met its primary endpoint and provides evidence for performing molecular testing of archival BM tissue, if available, to inform the choice of CNS-penetrant targeted therapy.
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