Fully reconfigurable MEMS-based second-order coupled-resonator optical waveguide (CROW) with ultra-low tuning energy.

Integrated microring resonators are well suited for wavelength-filtering applications in optical signal processing, and cascaded microring resonators allow flexible filter design in coupled-resonator optical waveguide (CROW) configurations. However, the implementation of high-order cascaded microring resonators with high extinction ratios (ERs) remains challenging owing to stringent fabrication requirements and the need for precise resonator tunability. We present a fully integrated on-chip second-order CROW filter using silicon photonic microelectromechanical systems (MEMS) to adjust tunable directional couplers and a phase shifter using nanoscale mechanical out-of-plane waveguide displacement. The filter can be fully reconfigured with regard to both the ER and center wavelength. We experimentally demonstrated an ER exceeding 25 dB and continuous wavelength tuning across the full free spectral range of 0.123 nm for single microring resonator, and showed reconfigurability in second-order CROW by tuning the ER and resonant wavelength. The tuning energy for an individual silicon photonic MEMS phase shifter or tunable coupler is less than 22 pJ with sub-microwatt static power consumption, which is far better than conventional integrated phase shifters based on other physical modulation mechanisms.

Programmable MZI based on a silicon photonic MEMS-tunable delay line.

We report on a scalable and programmable integrated Mach-Zehnder interferometer (MZI) with a tunable free spectral range (FSR) and extinction ratio (ER). For the tunable path of the MZI, we designed and utilized a tunable delay line having high flexibility based on silicon photonic microelectromechanical systems (MEMS). By utilizing MEMS, the length of the delay line can be geometrically modified. In this way, there is no optical loss penalty other than the waveguide propagation loss as the number of tunable steps increases. Therefore, our device is more scalable in terms of optical loss than the previous approaches based on cascaded MZIs. In addition, the tuning energy required to reconfigure the length is only 8.46 pJ.

Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer.

BACKGROUND: Limited accessibility of the tumour precludes longitudinal characterisation for therapy guidance in pancreatic ductal adenocarcinoma (PDAC). METHODS: We utilised dielectrophoresis-field flow fractionation (DEP-FFF) to isolate circulating tumour cells (CTCs) in 272 blood draws from 74 PDAC patients (41 localised, 33 metastatic) to non-invasively monitor disease progression. RESULTS: Analysis using multiplex imaging flow cytometry revealed four distinct sub-populations of CTCs: epithelial (E-CTC), mesenchymal (M-CTC), partial epithelial-mesenchymal transition (pEMT-CTC) and stem cell-like (SC-CTC). Overall, CTC detection rate was 76.8% (209/272 draws) and total CTC counts did not correlate with any clinicopathological variables. However, the proportion of pEMT-CTCs (prop-pEMT) was correlated with advanced disease, worse progression-free and overall survival in all patients, and earlier recurrence after resection. CONCLUSION: Our results underscore the importance of immunophenotyping and quantifying specific CTC sub-populations in PDAC.

Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer.

BACKGROUND & AIMS: We aimed to investigate the clinical utility of circulating tumor cell DNA (ctDNA) and exosome DNA (exoDNA) in pancreatic cancer. METHODS: We collected liquid biopsy samples from 194 patients undergoing treatment for localized or metastatic pancreatic adenocarcinoma from April 7, 2015, through October 13, 2017 (425 blood samples collected before [baseline] and during therapy). Additional liquid biopsy samples were collected from 37 disease control individuals. Droplet digital polymerase chain reaction was used to determine KRAS mutant allele fraction (MAF) from ctDNA and exoDNA purified from plasma. For the longitudinal analysis, we analyzed exoDNA and ctDNA in 123 serial blood samples from 34 patients. We performed analysis including Cox regression, Fisher exact test, and Bayesian inference to associate KRAS MAFs in exoDNA and ctDNA with prognostic and predictive outcomes. RESULTS: In the 34 patients with potentially resectable tumors, an increase in exoDNA level after neoadjuvant therapy was significantly associated with disease progression (P = .003), whereas ctDNA did not show correlations with outcomes. Concordance rates of KRAS mutations present in surgically resected tissue and detected in liquid biopsy samples were greater than 95%. On univariate analysis, patients with metastases and detectable ctDNA at baseline status had significantly shorter times of progression-free survival (PFS) (hazard ratio [HR] for death, 1.8; 95% CI, 1.1-3.0; P = .019), and overall survival (OS) (HR, 2.8; 95% CI, 1.4-5.7; P = .0045) compared with patients without detectable ctDNA. On multivariate analysis, MAFs ≥5% in exoDNA were a significant predictor of PFS (HR, 2.28; 95% CI, 1.18-4.40; P = .014) and OS (HR, 3.46; 95% CI, 1.40-8.50; P = .007). A multianalyte approach showed detection of both ctDNA and exoDNA MAFs ≥5% at baseline status to be a significant predictor of OS (HR, 7.73, 95% CI, 2.61-22.91, P = .00002) on multivariate analysis. In the longitudinal analysis, an MAF peak above 1% in exoDNA was significantly associated with radiologic progression (P = .0003). CONCLUSIONS: In a prospective cohort of pancreatic cancer patients, we show how longitudinal monitoring using liquid biopsy samples through exoDNA and ctDNA provides both predictive and prognostic information relevant to therapeutic stratification.

The use of indocyanine green fluorescence angiography to assess perfusion of chronic wounds undergoing hyperbaric oxygen therapy.

OBJECTIVE: The purpose of this study is to determine the utility of using indocyanine green fluorescence angiography (IGFA) in assessing perfusion of chronic wounds after hyperbaric oxygen (HBO2) therapy. METHODS: From May 2016 to January 2018, 26 patients underwent both HBO2 and IGFA. A near-infrared charge-coupled camera measured the flow of intravenous indocyanine green into the wound. IGFA was done pre-HBO2, after approximately 10 HBO2 sessions, and upon completion of HBO2. The ingress rate at baseline, mid-therapy and post-HBO2 values were compared using descriptive statistics. RESULTS: A total of 26 chronic wounds were identified. Baseline median ingress rate was 0.90 units/second (IQR: 0.28 to 6.10). Median ingress rate after approximately of 10 HBO2 sessions was 2.45 units/sec (IQR: 0.48 to 6.35). Six of 11 patients, however, exhibited a decrease in ingress rate from baseline to mid-therapy. Finally, median ingress rate post-HBO2 was 3.70 units/second (IQR: 0.30 to 9.90). Median increase in ingress and rate from baseline to mid-HBO2 treatment 0.30 units/second (IQR: -0.25 to 3.10) and from mid- to post-HBO2 was -0.40 units/second (IQR: -1.50 to 2.60). CONCLUSIONS: This preliminary study shows capability of IGFA to detect changes in blood flow to wounds following HBO2 therapy. Results support the use of IGFA to evaluate the changes in perfusion of patients undergoing HBO2 for chronic wounds. A larger sample size may help clarify the benefit of IGFA to predict potential for wound healing.

Changes in limpet diet according to habitat type.

Limpets are a key taxon regulating the benthic community structure and serving as prey for various predators in rocky shores, however, their role in food web dynamics is still unclear. To determine environmental factors influencing the limpet diet, carbon and nitrogen stable isotopes in limpets and food sources were analyzed on three different coastal habitats. Sediment organic matter contributed the most (86 %) to the limpet diet in bedrocks around tidal flats with abundant sediment supply from the terrestrial matter inflow and the sediment resuspension. Microphytobenthos and macroalgae were the main food sources (57 % and 20 %, respectively) for the limpets around beaches, where benthic flora was abundant. Limpets in bedrocks, erosional habitat, primarily consumed relatively abundant phytoplankton (33 %) and microphytobenthos (28 %). Contrary to previous studies, habitat type, rather than latitude or seawater characteristics, was the most important factor determining the limpet diet. This result also suggests that limpets are non-selective scraper that consume abundant food sources.

Integrated assessment of the natural purification capacity of tidal flat for persistent toxic substances and heavy metals in contaminated sediments.

Natural purification of pollutants is highly recognized as regulating ecosystem services; however, the purification capacity of tidal flats remains largely unknown and/or unquantified. A 60-day mesocosm transplant experiment was conducted in situ to assess the purification capacity of natural tidal flats. We adopted the advanced sediment quality triad approach, monitoring 10 endpoints, including chemical reduction, toxicity changes, and community recoveries. The results indicated that contaminated sediments rapidly recovered over time, particularly > 50% within a day, then slowly recovered up to âˆ¼ 70% in a given period (60 days). A significant early reduction of parent pollutants was evidenced across all treatments, primarily due to active bacterial decomposition. Notably, the presence of benthic fauna and vegetated halophytes in the treatments significantly enhanced the purification of pollutants in both efficacy and efficiency. A forecast linear modeling further suggested additive effects of biota on the natural purification of tidal flats, reducing a full recovery time from 500 to 300 days. Overall, the triad approach with machine learning practices successfully demonstrated quantitative insight into the integrated assessment of natural purification.

Ubiquitin-proteasome genes as targets for modulation of cisplatin sensitivity in fission yeast.

BACKGROUND: The ubiquitin(Ub)-proteasome pathway is implicated in the regulation of a variety of cellular functions and plays a major role in stress response in eukaryotic cells, by targeting misfolded and damaged proteins for degradation. In addition, in the presence of DNA damage, the Ub-proteasome system regulates proteins involved in sensing, repairing, and/or tolerating the damage. Antitumor agents such as cisplatin can activate the pathway, but the role of specific pathway components in cell sensitivity/response to the drug is not known. Since platinum compounds represent clinically relevant antitumor agents and a major limitation to their use is the development of drug resistance, there is an urgent need for identifying targets for improving their efficacy. RESULTS: In the present study, we performed a genome-wide screening for sensitivity to cisplatin using non-essential haploid deletion mutants of the fission yeast Schizosaccharomyces pombe, belonging to a collection of haploid strains constructed through homologous recombination. Using this approach, we identified three Ub-proteasome mutants exhibiting hypersensitivity to cisplatin (ubp16, ubc13 and pmt3) and ten mutants (including ufd2, beta7 20S, rpt6/let1) resistant to the drug. In addition, the importance of lub1 gene emerged from the comparison between the present screening and gene expression profile data previously obtained in fission yeast. CONCLUSIONS: The factors identified in the present study allowed us to highlight most finely the close relationship between the Ub-proteasome system and DNA damage response mechanisms, thus establishing a comprehensive framework of regulators likely relevant also in higher eukaryotes. Our results provide the proof of principle of the involvement of specific genes modulated by cisplatin treatment in cell response to the drug, suggesting their potential role as targets for modulating cisplatin sensitivity. In this regard, the prospective identification of novel targets for modulation of cisplatin sensitivity in an eukaryotic model organism appears particularly intriguing towards the discovery of strategies to overcome cisplatin resistance in human tumors.

Spatiotemporal variation of extracellular polymeric substances (EPS) associated with the microphytobenthos of tidal flats in the Yellow Sea.

The physical functions of extracellular polymeric substances (EPS), viz., by-product of microphytobenthos (MPB), in tidal flat system are well documented, but some ecological aspects remain unknown. We investigated MPB biomass (Chl-a), EPS, diatom assemblage, and erodibility in two contrasting tidal flat environments (megatidal vs. macrotidal flat) in the Yellow Sea. Thick biofilms were observed when MPB bloomed, with high Chl-a and increased EPS concentrations. Among diatom genera, Navicula was the most dominant taxa found over the year (mean 41%) in both areas. Compared with non-bloom periods, the erodibility decreased by 54-73% as biofilm thickened during the blooms. It was attributed to the elevated abundance of large-sized (>40 µm) Navicula, which was expected to secrete large amounts of EPS. Overall, we successfully demonstrated spatiotemporal differences of sediment stabilization that significantly related to ecological variations of MPB, and identified the key diatom genus as a "sediment stabilizer" in the typical tidal flats of the Yellow Sea.