The growth of wind energy is sustained by innovation that lowers the cost of energy. One recent innovation is the swept blade, which deflects in operation and lowers loads. With sweep, a design rotor ...diameter can increase, capturing more power, with the loads remaining within limits. This concept has been demonstrated in a U.S. program and is in commercial production. This paper describes a parametric study of swept blade design parameters for a 750 kW machine. The amount of tip sweep had the largest effect on the energy production and blade loads; other parameters had less impact. The authors then conducted a design study to implement a swept design on 1.5 MW, 3 MW, and 5 MW turbines. An aeroelastic code, previously described, was developed to model the behavior and determine the loads of the swept blade. The design goal was to increase annual energy production 5% over the straight blade, without increasing blade loads. Successful designs were developed for the 1.5 MW and 3.0 MW turbines. The swept 5 MW turbine exhibited a twist instability at high wind speeds. Further study is required to determine if sweep can be implemented for larger turbines, which are approaching flutter boundaries in unswept designs.
•Swept wind turbine blades offer possible reduced cost of energy-increased rotor diameter remaining in load limits.•Demonstrated in U.S. Dept. of Energy program and in commercial production (Siemens).•Parametric studies on 750 kW design to determine trends.•Concept scaled to 1.5 MW and 3 MW turbines.•5 MW turbine with sweep showed twist instability.
To provide proof of principle of safety, breast tumor-specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW ...targeting VEGF-A in patients with breast cancer.
Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and
in surgical specimens using an optical imaging system.
multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.
None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (
< 0.05) and healthy tissue (
< 0.0001). VEGF-A tumor levels also correlated with tracer levels (
= 0.63,
< 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected
by fluorescent macro- and microscopy and confirmed at the cellular level.
Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at
margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue.
.
The threshold to perform total pancreatectomy is rather high, predominantly because of concerns for long-term consequences of brittle diabetes on patients’ quality of life. Contemporary data on ...postoperative outcomes, diabetes management, and long-term quality of life after total pancreatectomy from large nationwide series are, however, lacking.
We performed a nationwide, retrospective cohort study among adults who underwent total pancreatectomy in 17 Dutch centers (2006–2016). Morbidity and mortality were analyzed, and long-term quality of life was assessed cross-sectionally using the following generic and disease-specific questionnaires: the 5-level version European quality of life 5-dimension and the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire Cancer. Several questionnaires specifically addressing diabetic quality of life included the Problem Areas in Diabetes Scale 20, the Diabetes Treatment Satisfaction Questionnaire-status version, and the Hypoglycemia Fear Survey-II. Results were compared with the general population and patients with type 1 diabetes.
Overall, 148 patients after total pancreatectomy were included. The annual nationwide volume of total pancreatectomy increased from 5 in 2006 to 32 in 2015 (P < .05). The 30-day and 90-day mortality were 5% and 8%, respectively. The major complication rate was 32%. Quality of life questionnaires were completed by 60 patients (85%, median follow-up of 36 months). Participants reported lower global (73 vs 78, P = .03) and daily health status (0.83 vs 0.87, P < .01) compared to the general population. Quality of life did not differ based on time after total pancreatectomy (<3, 3–5, or >5 years). In general, patients were satisfied with their diabetes therapy and experienced similar diabetes-related distress as patients with type 1 diabetes.
This nationwide study found increased use of total pancreatectomy with a relatively high 90-day mortality. Long-term quality of life was lower compared to the general population, although differences were small. Diabetes-related distress and treatment satisfaction were similar to patients with type 1 diabetes.
Outpatient delivery of geriatric rehabilitation (GR) might contribute to preserving the accessibility and quality of GR, whilst dealing with an increasing demand for healthcare in an aging ...population. However, the application of outpatient GR differs between GR facilities. This study aimed to gain insight into factors influencing outpatient GR utilization.
In this case study, 24 semi-structured interviews were conducted with physicians, physiotherapists, nurse practitioners, occupational therapists, and managers in GR. Interviews were transcribed and analyzed using summative content analysis.
Various patient-related barriers for using outpatient GR were mentioned including lacking social support and limited capacities and self-management skills. Additionally, professional-related barriers included a lack of awareness and consensus among care professionals regarding the possibilities and potential advantages of outpatient GR. Yet, most perceived barriers were related to efficiency and organization of outpatient GR (e.g., reimbursement system, lacking practical guidance). Still, most participants were in favor of increasing outpatient GR because of expected advantages for patients, GR organizations, and society.
Despite experienced barriers, there seems to be agreement on the need to increase outpatient GR application. It is recommended to use the present findings to develop and evaluate new ways of organizing and reimbursing outpatient GR.
Tissue-resident memory CD8
T cells (T
) constitute a noncirculating memory T cell subset that provides early protection against reinfection. However, how T
arise from antigen-triggered T cells has ...remained unclear. Exploiting the T
-restricted expression of Hobit, we used T
reporter/deleter mice to study T
differentiation. We found that Hobit was up-regulated in a subset of LCMV-specific CD8
T cells located within peripheral tissues during the effector phase of the immune response. These Hobit
effector T cells were identified as T
precursors, given that their depletion substantially decreased T
development but not the formation of circulating memory T cells. Adoptive transfer experiments of Hobit
effector T cells corroborated their biased contribution to the T
lineage. Transcriptional profiling of Hobit
effector T cells underlined the early establishment of T
properties including down-regulation of tissue exit receptors and up-regulation of T
-associated molecules. We identified Eomes as a key factor instructing the early bifurcation of circulating and resident lineages. These findings establish that commitment of T
occurs early in antigen-driven T cell differentiation and reveal the molecular mechanisms underlying this differentiation pathway.
High quantum yield, photoluminescence tunability, and sensitivity to the environment are hallmarks that make carbon nanodots interesting for fundamental research and applications. Yet, the underlying ...electronic transitions behind their bright photoluminescence are strongly debated. Despite carbon-dot interactions with their environment should provide valuable insight into the emitting transitions, they have hardly been studied. Here, we investigate these interactions in a wide range of solvents to elucidate the nature of the electronic transitions. We find remarkable and systematic dependence of the emission energy and kinetics on the characteristics of the solvent, with strong response of the photoexcited dots to hydrogen bonding. These findings suggest that the fluorescence originates from the radiative recombination of a photoexcited electron migrated to surface groups with holes left in the valence band of the crystalline core. Furthermore, the results demonstrate the fluorescence tunability to inherently derive from dot-to-dot polydispersity, independent of solvent interactions.
NG-Tax 2.0 is a semantic framework for FAIR high-throughput analysis and classification of marker gene amplicon sequences including bacterial and archaeal 16S ribosomal RNA (rRNA), eukaryotic 18S ...rRNA and ribosomal intergenic transcribed spacer sequences. It can directly use single or merged reads, paired-end reads and unmerged paired-end reads from long range fragments as input to generate
amplicon sequence variants (ASV). Using the RDF data model, ASV's can be automatically stored in a graph database as objects that link ASV sequences with the full data-wise and element-wise provenance, thereby achieving the level of interoperability required to utilize such data to its full potential. The graph database can be directly queried, allowing for comparative analyses of over thousands of samples and is connected with an interactive Rshiny toolbox for analysis and visualization of (meta) data. Additionally, NG-Tax 2.0 exports an extended BIOM 1.0 (JSON) file as starting point for further analyses by other means. The extended BIOM file contains new attribute types to include information about the command arguments used, the sequences of the ASVs formed, classification confidence scores and is backwards compatible. The performance of NG-Tax 2.0 was compared with DADA2, using the plugin in the QIIME 2 analysis pipeline. Fourteen 16S rRNA gene amplicon mock community samples were obtained from the literature and evaluated. Precision of NG-Tax 2.0 was significantly higher with an average of 0.95 vs 0.58 for QIIME2-DADA2 while recall was comparable with an average of 0.85 and 0.77, respectively. NG-Tax 2.0 is written in Java. The code, the ontology, a Galaxy platform implementation, the analysis toolbox, tutorials and example SPARQL queries are freely available at http://wurssb.gitlab.io/ngtax under the MIT License.
The immunosuppressive character of head and neck cancers may explain the relatively low response rates to antibody therapy targeting a tumor antigen, such as cetuximab, and anti-PD-1 checkpoint ...inhibition. Immunostimulatory agents that overcome tumor-derived inhibitory signals could augment therapeutic efficacy, thereby enhancing tumor elimination and improving patient survival. Here, we demonstrate that cetuximab treatment combined with immunostimulatory agonists for Toll-like receptor (TLR) 2 induces profound immune responses. Natural killer (NK) cells, isolated from healthy individuals or patients with head and neck cancer, harbored enhanced cytotoxic capacity and increased tumor-killing potential in vitro. Additionally, combination treatment increased the release of several pro-inflammatory cytokines and chemokines by NK cells. Tumor-bearing mice that received cetuximab and the TLR2 ligand Pam3CSK4 showed increased infiltration of immune cells into the tumors compared to mice that received cetuximab monotherapy, resulting in a significant delay in tumor growth or even complete tumor regression. Moreover, combination treatment resulted in improved overall survival in vivo. In conclusion, combining tumor-targeting antibody-based immunotherapy with TLR stimulation represents a promising treatment strategy to improve the clinical outcomes of cancer patients. This treatment could well be applied together with other therapeutic strategies such as anti-PD-(L)1 checkpoint inhibition to further overcome immunosuppression.
The ability to manipulate droplets on a substrate using electric signals
-known as digital microfluidics-is used in optical
, biomedical
, thermal
and electronic
applications and has led to ...commercially available liquid lenses
and diagnostics kits
. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)
; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown
, electric charging
and biofouling
. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.
PDF
