Photonic structures can be designed to tailor luminescence properties of materials, which becomes particularly interesting for non-linear phenomena, such as photon upconversion. However, there is no ...adequate theoretical framework to optimize photonic structure designs for upconversion enhancement. Here, we present a comprehensive theoretical model describing photonic effects on upconversion and confirm the model's predictions by experimental realization of 1D-photonic upconverter devices with large statistics and parameter scans. The measured upconversion photoluminescence enhancement reaches 82 ± 24% of the simulated enhancement, in the mean of 2480 separate measurements, scanning the irradiance and the excitation wavelength on 40 different sample designs. Additionally, the trends expected from the modeled interaction of photonic energy density enhancement, local density of optical states and internal upconversion dynamics, are clearly validated in all experimentally performed parameter scans. Our simulation tool now opens the possibility of precisely designing photonic structure designs for various upconverting materials and applications.
Lung branching morphogenesis requires reciprocal interactions between the epithelium and mesenchyme. How the lung branches are generated at a defined location and projected toward a specific ...direction remains a major unresolved issue. In this study, we investigated the function of Wnt signaling in lung branching in mice. We discovered that Wnt5a in both the epithelium and the mesenchyme plays an essential role in controlling the position and direction of lung branching. The Wnt5a signal is mediated by Vangl1/2 to trigger a cascade of noncanonical or planar cell polarity (PCP) signaling. In response to noncanonical Wnt signaling, lung cells undergo cytoskeletal reorganization and change focal adhesions. Perturbed focal adhesions in lung explants are associated with defective branching. Moreover, we observed changes in the shape and orientation of the epithelial sheet and the underlying mesenchymal layer in regions of defective branching in the mutant lungs. Thus, PCP signaling helps define the position and orientation of the lung branches. We propose that mechanical force induced by noncanonical Wnt signaling mediates a coordinated alteration in the shape and orientation of a group of epithelial and mesenchymal cells. These results provide a new framework for understanding the molecular mechanisms by which a stereotypic branching pattern is generated.
Post-translational palmitoylation of intracellular proteins is mediated by protein palmitoyltransferases belonging to the DHHC family, which share a common catalytic Asp-His-His-Cys (DHHC) motif. ...Several members have been implicated in neuronal development, neurotransmission, and synaptic plasticity. We previously observed that mice homozygous for a hypomorphic allele of the ZDHHC5 gene are impaired in context-dependent learning and memory. To identify potentially relevant protein substrates of DHHC5, we performed a quantitative proteomic analysis of stable isotope-labeled neuronal stem cell cultures from forebrains of normal and DHHC5-GT (gene-trapped) mice using the bioorthogonal palmitate analog 17-octadecynoic acid. We identified ∼300 17-octadecynoic acid-modified and hydroxylamine-sensitive proteins, of which a subset was decreased in abundance in DHHC5-GT cells. Palmitoylation and oligomerization of one of these proteins (flotillin-2) was abolished in DHHC5-GT neuronal stem cells. In COS-1 cells, overexpression of DHHC5 markedly stimulated the palmitoylation of flotillin-2, strongly suggesting a direct enzyme-substrate relationship. Serendipitously, we found that down-regulation of DHHC5 was triggered within minutes following growth factor withdrawal from normal neural stem cells, a maneuver that is used to induce neural differentiation in culture. The effect was reversible for up to 4 h, and degradation was partially prevented by inhibitors of ubiquitin-mediated proteolysis. These findings suggest that protein palmitoylation can be regulated through changes in DHHC PAT levels in response to differentiation signals.
Background: The substrates and regulation of DHHC protein palmitoyl acyltransferases (PATs) are largely unknown.
Results: Flotillin-2 palmitoylation is abolished in DHHC5 gene-targeted neural stem cells, and neuronal differentiation induces DHHC5 turnover.
Conclusion: Flotillin-2 is a substrate for DHHC5, which is regulated at the protein level.
Significance: The paper describes an approach to PAT substrate identification and a new PAT regulation mechanism.
Vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) combines the advantages of vaginal surgery with those of laparoscopic surgery. Feasibility of vNOTES for other indications such as ...hysterectomy, ovarian cystectomy and myomectomy has been established. In this article, we describe a standardised step by step process to perform adnexal surgery by vNOTES.
Head and neck cancers (HNSCC) are highly immunosuppressive. Plasma-derived exosomes of HNSCC patients carry immunomodulatory molecules, and their cargo correlates with clinical parameters. Here, we ...evaluated the exosomal molecular profile for early detection of treatment failure in locally advanced HNSCC patients treated with conventional therapy.
Plasma from 17 HNSCC patients was collected before, during, and after treatment by surgery with adjuvant (chemo)radiation and at recurrence. Exosomes were isolated by size-exclusion chromatography. Total exosomal protein (TEP) was used to estimate exosome load and on-bead flow cytometry to evaluate relative fluorescence intensity (RFI) of tumour-associated and immunoregulatory proteins on exosomes. Exosomal effects on the activity of and adenosine production by T cells was assessed by flow cytometry and mass spectrometry.
TEP and the ratio of tumour-/immune-cell-derived exosomes varied during and after therapy with an overall decrease in the tumour-free follow-up but an increase at recurrence. RFI values of immunoregulatory proteins on exosomes, their ability for T cell inhibition and adenosine production changed during and after therapy. PD-L1 was the earliest discriminator for treatment failure and disease-free survival.
Monitoring of plasma exosomes during therapy represents a promising opportunity for early detection of treatment failure and risk stratification to delay/avoid recurrence.
In this paper, we present a comprehensive simulation-based analysis of the two photonic effects of a Bragg stack - a modified local density of photon states (LDOS) and an enhanced local irradiance - ...on the upconversion (UC) luminescence and quantum yield of the upconverter β-NaYF
doped with 25% Er
. The investigated Bragg stack consists of alternating layers of TiO
and Poly(methylmethacrylate), the latter containing upconverter nanoparticles. Using experimentally determined input parameters, the photonic effects are first simulated separately and subsequently coupled in a rate equation model, describing the dynamics of the UC processes within β-NaYF
:25% Er
. With this integrated simulation model, the Bragg stack design is optimized to maximize either the UC quantum yield (UCQY) or UC luminescence. We find that in an optimized Bragg stack, due to the modified LDOS, the maximum UCQY is enhanced from 14% to 16%, compared to an unstructured layer of upconverter material. Additionally, this maximum UCQY can already be reached at an incident irradiance as low as 100 W/m
. With a Bragg stack design that maximizes UC luminescence, enhancement factors of up to 480 of the UC luminescence can be reached.
Purpose
This study aimed to investigate functional outcome and complications after primary and revision modular H-TKA using hybrid fixation with cementless stems.
Methods
Between 2015 and 2018, 48 ...patients with 50 implants were included after hybrid implantation of a single design H-TKA system using cementless osseointegrating stems and modular components. Complications and clinical outcome were analysed using Knee Society Score (KSS), the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) and the Short-Form Health Survey 12 (SF-12) score.
Results
Indications for implantation were aseptic revision (
n
= 29, 58%), primary TKA (
n
= 19, 38%) and two-stage septic revisions (
n
= 2, 4%). Complications were reported in 26% (
n
= 12), whereas complications associated with hybrid fixation occurred in 5 (10%) cases, with 2 (4%) requiring revision surgery for aseptic loosening and 3 (6%) treated with an adapted postoperative protocol for perioperative fractures. Implant survivorship was 84% after a mean follow-up of 54 months. Postoperative KSS significantly improved from 51.50 (12–100) to 78.36 (41–99;
p
< 0.001). The mean WOMAC score was 19.26 (0–55), SF-12 PCS was 41.56 points (22.67–57.66) and SF-12 MCS was 49.21 points (23.87–63.21).
Conclusion
Hybrid modular implantation in H-TKA provides satisfactory clinical and functional results in primary and revision TKA. Clinical outcomes significantly improve with reduced pain, increased mobility, and good-to-excellent functional scores after implantation. Whilst implant survival is comparable to previous studies and complications associated with hybrid fixation are low, general complication rates are comparably high.
Adequately accounting for interactions between Low Carbon Technologies (LCTs) at the building level and the overarching energy system means capturing the granularity associated with decentralised ...heat and power supply in residential buildings. The approach presented here adds novelty in terms of a realistic socioeconomic differentiation by employing dwelling/household archetypes (DHAs) and neighbourhood clusters at the Output Area (OA) level. These archetypes are combined with a mixed integer linear program (MILP) to generate optimum (minimum cost) technology configurations and operation schedules. Even in the baseline case, without any LCT penetration, a substantial deviation from the standard load profile (SLP) is encountered, suggesting that for some neighbourhoods this profile is not appropriate. With the application of LCTs, including heat pumps, micro-CHP and photovoltaic (PV), this effect is much stronger, including more negative residual load, more variability, and higher ramps with increased LCT penetration, and crucially different between neighbourhood clusters. The main policy implication of the study is the importance of understanding electrical load profiles at the neighbourhood level, because of the consequences they have for investment in the overarching energy system, including transmission and distribution infrastructure, and centralised generation plant. Further work should focus on attaining a superior socioeconomic differentiation between households.
•Low carbon technologies (LCTs) for heat/electricity in residential buildings.•Socioeconomic effects and interactions with overarching energy system.•Building thermal/electrical model combined with optimisation.•Significant differences between neighbourhood load profiles.•Policy implications: support for LCTs and investment in infrastructure.
Electron paramagnetic resonance (EPR) spectroscopy has become a promising structural biology tool to resolve complex and dynamic biological mechanisms
in-vitro
and
in-cell
. Here, we focus on the ...advantages of continuous wave (CW) and pulsed EPR distance measurements to resolve transcription processes and protein-DNA interaction. The wide range of spin-labeling approaches that can be used to follow structural changes in both protein and DNA render EPR a powerful method to study protein-DNA interactions and structure–function relationships in other macromolecular complexes. EPR-derived data goes well beyond static structural information and thus serves as the method of choice if dynamic insight is needed. Herein, we describe the conceptual details of the theory and the methodology and illustrate the use of EPR to study the protein-DNA interaction of the copper-sensitive transcription factor, CueR.
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