Real-time Profiles Research Articles

Real-time biomonitoring of oxygen uptake rate and biochemical oxygen demand using a novel optical biogas respirometric system

In response to the ever-increasing need for monitoring-based process control of wastewater treatment plants, an online applicable respirometer shows great promise for real-time measurement of oxygen uptake rate (OUR) and biochemical oxygen demand (BOD) measurements as a surrogate of the biodegradability of wastewater. Here, we have developed a photosensor-assisted real-time respirometric system equipped with bubble counting sensors for accurate measurement of microbial oxygen consumption in a bottle. This system can measure OUR and BOD in a bottle equipped with a tube containing NaOH solution to absorb carbon dioxide and supplied with continuous atmospheric oxygen to the bottle, which reliably supplies non-limiting dissolved oxygen (DO) for aerobic biodegradation even at high organic loads. These technical improvements allow a sensitive and rapid analytical tool offering real-time profiles of oxygen uptake rate as well as BOD measurements with an extended measurable range (0–420 mg O2/L), enabling significant reduction or elimination of dilution steps. The respirometric system was used to elucidate the biodegradable kinetics of domestic and swine wastewaters as a function of the type and concentration of organic matters, depending on source characteristics including rapidly or slowly oxidizable organic substances by bacteria. Compared with conventional and manometric BOD methods, our method is reliable and accurate.

Observation of vertical wind profiling with lidar based on correction of sensitivity.

A high spectral resolution lidar (HSRL) for simultaneously detecting vertical wind, temperature, and the backscattering ratio in the troposphere is developed. The atmospheric temperature and vertical wind are determined by the Rayleigh scattering spectrum width and Mie scattering spectrum Doppler shift, respectively. The influence of temperature and the backscattering ratio on vertical wind measurement accuracy is also analyzed. The temperature and backscattering ratio affect the wind measurement, which produces the vertical wind offset. A correction considering the effects of the method is conducted considering real-time and on-site temperature profiles and the backscattering ratio to correct wind measurement sensitivity. Measurements of HSRL taken under different weather conditions (fine and hazy days) are demonstrated. Good agreement between the HSRL and the radiosonde measurements was obtained considering lapse rates and temperature inversions. The maximum temperature offsets were 1.3 and 4 K at a height of 1.5 km on fine and hazy days, respectively. Then, real-time and on-site temperature profiles and backscattering ratios were applied to correct the real-time and on-site wind. The corrected wind profiles showed satisfactory agreement with the wind profiles acquired from the calibrated wind lidar. The maximum detection offsets of the retrieved wind speed were reduced from 1 m/s to 0.55 m/s and from 1 m/s to 0.21 m/s, respectively, which were decreases of 0.45 and 0.79 m/s in fine and hazy days after correction of sensitivity. It is evident that the corrected wind method can reduce the influence of temperature and the backscattering ratio on the wind measurement and the offset of vertical wind. The reliability of the method is also proven.

Field Measurements of Soil Water Content at Shallow Depths for Landslide Monitoring

Monitoring changes in soil saturation is important for slope stability analyses. Soil moisture capacitive sensors have recently been developed; their response time is extremely fast, they require little maintenance, and they are relatively inexpensive. The use of low-cost sensors in landslide areas can allow the monitoring of large territories, but appropriate calibration is required. Installation in the field and the setting up of the monitoring network also require attention. In the ALCOTRA AD-VITAM project, the University of Genoa is involved in the development of a system, called LAMP, for the monitoring, analysis and forecasting of slides triggered by rainfalls. Multiple installations (along vertical alignments) of WaterScout sensors are placed in the nodes of the monitoring network. They provide real-time water content profiles in the shallow layers (typically in the upper meter) of a slope. With particular reference to these measurements, the present paper describes the reliability analysis of the instruments, the operations related to the sensor calibration and the installation phases for the monitoring networks. Finally, some of the data coming from a node, belonging to one of the five monitoring networks, are reported.

A 6.5-kb intergenic structural variation enhances P450-mediated resistance to pyrethroids in malaria vectors lowering bed net efficacy.

Elucidating the complex evolutionary armory that mosquitoes deploy against insecticides is crucial to maintain the effectiveness of insecticide-based interventions. Here, we deciphered the role of a 6.5-kb structural variation (SV) in driving cytochrome P450-mediated pyrethroid resistance in the malaria vector, Anopheles funestus. Whole-genome pooled sequencing detected an intergenic 6.5-kb SV between duplicated CYP6P9a/b P450s in pyrethroid-resistant mosquitoes through a translocation event. Promoter analysis revealed a 17.5-fold higher activity (p<.0001) for the SV- carrying fragment than the SV- free one. Quantitative real-time PCR expression profiling of CYP6P9a/b for each SV genotype supported its role as an enhancer because SV+/SV+ homozygote mosquitoes had a significantly greater expression for both genes than heterozygotes SV+/SV- (1.7- to 2-fold) and homozygotes SV-/SV- (4-to 5-fold). Designing a PCR assay revealed a strong association between this SV and pyrethroid resistance (SV+/SV+ vs. SV-/SV-; odds ratio [OR]=2,079.4, p<.001). The 6.5-kb SV is present at high frequency in southern Africa (80%-100%) but absent in East/Central/West Africa. Experimental hut trials revealed that homozygote SV mosquitoes had a significantly greater chance to survive exposure to pyrethroid-treated nets (OR 27.7; p<.0001) and to blood feed than susceptible mosquitoes. Furthermore, mosquitoes homozygote-resistant at the three loci (SV+/CYP6P9a_R/CYP6P9b_R) exhibited a higher resistance level, leading to a far superior ability to survive exposure to nets than those homozygotes susceptible at the three loci, revealing a strong additive effect. This study highlights the important role of structural variations in the development of insecticide resistance in malaria vectors and their detrimental impact on the effectiveness of pyrethroid-based nets.

Novel method for real-time burden profile measurement at blast furnace

ABSTRACT The operation of the furnace depends largely on the handling of gas distribution. Charging of materials in the furnace is thus one of the most important control signals. International studies have been conducted with the aim of understanding the charging machinery and its influence on the distribution of materials, e.g. angle of repose and charging materials that meet the properties. This evaluation aims at finding the optimum technique for designing an instrument which can provide continuous real-time 3-D burden surface profile measurement at blast furnace.

Circulating tumour DNA in metastatic breast cancer to guide clinical trial enrolment and precision oncology: Acohort study.

BackgroundMetastatic breast cancer (mBC) is a heterogenous disease with increasing availability of targeted therapies as well as emerging genomic markers of therapeutic resistance, necessitating timely and accurate molecular characterization of disease. As a minimally invasive test, analysis of circulating tumour DNA (ctDNA) is well positioned for real-time genomic profiling to guide treatment decisions. Here, we report the results of a prospective testing program established to assess the feasibility of ctDNA analysis to guide clinical management of mBC patients.Methods and findingsTwo hundred thirty-four mBC patients (median age 54 years) were enrolled between June 2015 and October 2018 at the Peter MacCallum Cancer Centre, Melbourne, Australia. Median follow-up was 15 months (range 1–46). All patient samples at the time of enrolment were analysed in real time for the presence of somatic mutations. Longitudinal plasma testing during the course of patient management was also undertaken in a subset of patients (n = 67, 28.6%), according to clinician preference, for repeated molecular profiling or disease monitoring. Detection of somatic mutations from patient plasma was performed using a multiplexed droplet digital PCR (ddPCR) approach to identify hotspot mutations in PIK3CA, ESR1, ERBB2, and AKT1. In parallel, subsets of samples were also analysed via next-generation sequencing (targeted panel sequencing and low-coverage whole-genome sequencing [LC-WGS]). The sensitivity of ddPCR and targeted panel sequencing to identify actionable mutations was compared. Results were discussed at a multidisciplinary breast cancer meeting prior to treatment decisions. ddPCR and targeted panel sequencing identified at least 1 actionable mutation at baseline in 80/234 (34.2%) and 62/159 (39.0%) of patients tested, respectively. Combined, both methods detected an actionable alteration in 104/234 patients (44.4%) through baseline or serial ctDNA testing. LC-WGS was performed on 27 patients from the cohort, uncovering several recurrently amplified regions including 11q13.3 encompassing CCND1. Increasing ctDNA levels were associated with inferior overall survival, whether assessed by ddPCR, targeted sequencing, or LC-WGS. Overall, the ctDNA results changed clinical management in 40 patients including the direct recruitment of 20 patients to clinical trials. Limitations of the study were that it was conducted at a single site and that 31.3% of participants were lost to follow-up.ConclusionIn this study, we found prospective ctDNA testing to be a practical and feasible approach that can guide clinical trial enrolment and patient management in mBC.

303 Poster - Real-time non-invasive chemoresistance profiling of circulating tumor associated cells in breast cancers to determine resistance towards mitotic inhibitors

Background: Paclitaxel, Docetaxel and Vinorelbine exert anti-tumor activity by interfering with microtubule dynamics, leading to mitotic arrest. Though these agents are commonly used in treatment of breast cancers, therapy failures are noted due to innate and acquired chemoresistance. Real-time monitoring of chemoresistance towards such treatment agents is an unmet clinical need since conventional methods for chemoresistance profiling (CRP) necessitate invasive biopsies to obtain viable tumor tissue. We evaluated the utility of peripheral blood Circulating Tumor Associated Cells (C-TACs) for real-time non-invasive CRP in breast cancers.

A Novel Method for Designing Motion Profiles Based on a Fuzzy Logic Algorithm Using the Hip Joint Angles of a Lower-Limb Exoskeleton Robot

In this study, a novel method for designing real-time motion profiles based on a weighted fuzzy logic algorithm for an exoskeleton robot was proposed. When developing exoskeleton robots, it is important that they can identify a wearer’s motion intent in real time; therefore, we produced the motion profiles of an exoskeleton robot knee joint angles using hip joint angles and plantar pressure sensors. Two types of sensors were used to design the robot’s knee estimation angle profiles in real time—namely, hip joint angles to design the fuzzy logic algorithm and plantar pressure sensors to classify the robot’s gait phase. In the fuzzy set, four fuzzy inputs were produced through the hip joint angles; then, four fuzzy outputs were implemented based on the fuzzy inputs using 68 predefined rule bases in the fuzzy inference. The fuzzy outputs were used as the basis for calculating the motion profiles during the defuzzification. To adjust the knee angle of the robot, the weighted values were assigned to each hip joint angle section. To validate the proposed algorithm, we conducted two experiments—namely, the exoskeleton robot with and without an actuator. The method was verified through experiments showing that the motion profiles estimated the robot’s knee angles close to the desired angles.

Cycle-to-Cycle Multipulse Fuel-Injection Control for Advanced Diesel Combustion in Changing and Disturbed Operating Points

Abstract When controlled in an open-loop fashion, both stationary and dynamical diesel engine performance can deteriorate due to disturbances. Although cycle-to-cycle fuel injection control has the potential of reducing the performance degradation by manipulating the fueling profile in real time, this potential has not been thoroughly studied. This is especially true for multipulse fuel injection, due to the lack of a controller design method with closed-loop reference tracking performance guarantees. In this paper, we introduce a systematic design method for multivariable cycle-to-cycle fuel injection control. The design method is based on several local linearizations to address varying combustion behavior due to different engine speeds, torques, and disturbances. This leads to a controller that is robust with respect to all the local linearizations. Experimental results show that the controller works well in both stationary and dynamical operating conditions, and has fast dynamical performance (settling time less than 1.5 (s)). Moreover, experimental data show that cycle-to-cycle fuel injection control is robust against the uncertainties introduced by disturbed rail pressure and swirl valve position.

Updates on the treatment of adhesive capsulitis with hydraulic distension.

Adhesive capsulitis of the shoulder joint is a common disease characterized by pain at the insertional area of the deltoid muscle and decreased range of motion. The pathophysiological process involves fibrous inflammation of the capsule and intraarticular adhesion of synovial folds leading to capsular thickening and contracture. Regarding the multidirectional limitation of motion, a limitation in external rotation is especially prominent, which is related to not only global fibrosis but also to a localized tightness of the anterior capsule. Ultrasound and magnetic resonance imaging studies can be applied to rule out other structural lesions in the diagnosis of adhesive capsulitis. Hydraulic distension of the shoulder joint capsule provides pain relief and an immediate improvement in range of motion by directly expanding the capsule along with the infusion of steroids. However, the optimal technique for hydraulic distension is still a matter of controversy, with regards to the infusion volume and rupture of the capsule. By monitoring the real-time pressure-volume profile during hydraulic distension, the largest possible fluid volume can be infused without rupturing the capsule. The improvement in clinical outcomes is shown to be greater in capsule-preserved hydraulic distension than in capsule-ruptured distension. Moreover, repeated distension is possible, which provides additional clinical improvement. Capsule-preserved hydraulic distension with maximal volume is suggested to be an efficacious treatment option for persistent adhesive capsulitis.

Characterization and overexpression of sterol Δ22-desaturase, a key enzyme modulates the biosyntheses of stigmasterol and withanolides in Withania somnifera (L.) Dunal

Withanolides constitute an extensive and vital class of metabolites displaying wide array of structural and therapeutic properties with unique side-chain modifications. These show diversified scaffolds and are promising pharmaceutical molecules with well documented anti-inflammatory and anti-cancer properties. Sterols are dynamic class of compounds and essential molecules having structural and functional significance. These contribute to the synthesis of withanolides by providing structural precursors. In this context, we have characterized sterol Δ22-desaturase from Withania somnifera and also functionally validating it by confirming its desaturase nature in conjunction with quantitative real-time expression profiling and metabolite evaluation. Further, transgenic hairy roots of W. somnifera displayed a higher accumulation of stigmasterol and withanolides. The increase in chemical constituents was concomitant with an increased gene copy number predicted via Southern blotting. Additionally, transgenic lines of tobacco over-expressing WsCYP710A11 displayed a substantial increase in its expression, corroborating well with enhanced stigmasterol content. Characterization of CYP710A11 from W. somnifera and its homologous transgenic expression has demonstrated its role in the regulation of withanolides biosynthesis. It also exhibited a differential transcriptional profile in response to exogenous elicitations. These empirical findings suggest the crucial role of CYP710A11 in stigmasterol biosynthesis. This in turn has implications for the overproduction of withanolides via pathway channelling.

Abstract SY09-01: A comprehensive European approach to precision pediatric cancer medicine

Abstract Cure rates for pediatric malignancies have stagnated at around 80% for two decades. A “more of the same” approach will likely not help a considerable proportion of the remaining ~20% of children who cannot be cured to date, thus implying an urgent need for innovative treatment strategies. The aim of the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) program is to translate next generation molecular diagnostics into a personalized, biomarker-driven treatment strategy. The program consists of two major pillars: the INFORM registry providing a molecular screening platform and the INFORM2 series of exploratory biomarker-driven phase I/II trials, conducted through the European Innovative Therapies for Children with Cancer (ITCC) network. This is complemented by an international public-private preclinical testing platform, ITCC-P4, which aims at systematic and rigorous preclinical filtering of novel assets for a potential indication in the pediatric space. INFORM is a multi-national registry, open across nine European countries, offering comprehensive real-time molecular profiling for pediatric patients with no standard treatment options. INFORM is complemented by corresponding programs in France, the Netherlands, the UK and Denmark to cover most of the European population. To date, more than 1,100 patients have been registered and profiled through INFORM, using whole-exome and low-coverage whole genome sequencing, as well as RNA transcriptome sequencing and DNA methylation analysis. In 2019 alone, almost 400 patients were recruited. A comprehensive analysis of the first ~800 patients enrolled including a thorough primary-relapse study to investigate intra-individual tumor evolution is currently ongoing and first results will be presented. Potentially actionable targets of ‘moderate' or higher priority (which are reported in the weekly interdisciplinary molecular tumor board and documented in the online database) were identified in approximately half of all patients, with many having been treated with mechanism-of-action based therapies on the basis of the generated data. Recently we have also added real-time drug profiling on short-term tumor cell cultures as an additional screening tool in the context of the COMPASS Consortium. The long-term goals of this program are 1) to inform a series of early-phase, cross-entity, combination clinical trials to improve access to innovative treatment approaches for pediatric patients (e.g., INFORM2 trial series); and 2) to deliver evidence demonstrating that the molecular profiling is of clinical value to patients, in the assumption that these costs will be reimbursed by health insurances as part of routine standard-of-care for high-risk pediatric cancer patients. Within the preclinical platform ITCC-P4, consortium members have established and molecularly characterized more than 150 patient-derived xenograft models from pediatric solid tumors (target: 400 models). These are now being utilized for systematic single-mouse preclinical trials applying both standard-of-care treatments as well as innovative new drugs from the portfolios of participating companies in selected pediatric cancer (sub)-entities through standardized Mechanism-of-Action-based matching with pediatric tumor biology. Applying a uniform and comprehensive interdisciplinary strategy for molecular diagnostic, preclinical and early clinical activities in Europe, we hope to be able to tackle the challenge of pediatric very high-risk diseases in a more effective way. Citation Format: Stefan M. Pfister, David TW Jones, Barbara C. Jones, Balasubramanian Gnana Prakash, Mirjam Blattner-Johnson, Elke Pfaff, Cornelis M. Van Tilburg, Sina Oppermann, Louis Stancato, Hubert Caron, Gilles Vassal, Kristian Pajtler, Natalie Jäger, Olaf Witt. A comprehensive European approach to precision pediatric cancer medicine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr SY09-01.

Abstract 5727: Metabolic status and adaptability of breast cancer stem cells

Abstract Breast cancer stem cells (BCSCs) represent the subpopulation of malignant cells that cause tumor initiation, metastasis, and recurrence. BCSCs resist therapy with radiation and standard drugs, emphasizing the need to identify new vulnerabilities as therapeutic targets. Here, we investigated the metabolism of BCSCs at single-cell resolution using molecular imaging and scRNA sequencing techniques. We imaged retention of the fluorescent dye PKH26 or expression of a CRISPR/Cas9-engineered ALDH1A3-mCherry promoter-reporter to identify BCSCs and metabolic state of cells by two-photon microscopy with fluorescence lifetime imaging (FLIM) of endogenous NADH. We previously reported that sorted BCSCs exhibited enhanced metabolic plasticity relative to bulk tumor cells in 2D culture and rapidly metabolically adapted to the glycolysis inhibitor 2-deoxyglucose (2DG). Since cells rewire signaling and metabolism in 3D environments, we utilized two-photon microscopy to quantify metabolism in secondary mammospheres and living animals. In both intact spheres and orthotopic tumor xenografts, BCSCs marked by either fluorescent reporter utilized glycolysis to a greater extent than bulk cancer cells. We validated our findings by correlating cellular entropy as a marker for cancer stem cells with metabolic pathway preferences on a single-cell basis. When treated with 2DG, mammospheres showed increased OXPHOS and a significant decrease in the percentage of ALDH1A3-mCherry+ cells. These data 1) highlight capabilities of FLIM to measure the metabolism of single cancer cells in physiologic environments; 2) correlate molecular phenotypes with real-time molecular imaging profiles of metabolism and stem-ness; and 3) reveal that BCSCs rely on glycolysis, suggesting a potential target for metabolic therapy. Citation Format: Johanna M. Buschhaus, Ayse J. Muniz, Ming Luo, Joseph P. Burnett, Nathan A. Truchan, Michael D. Brooks, Brock A. Humphries, Kathy E. Luker, Joerg Lahann, Duxin Sun, Max S. Wicha, Gary D. Luker. Metabolic status and adaptability of breast cancer stem cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5727.

Abstract 2489: Characterization of breast cancer ctDNA with Omi-Seq

Abstract Cancer patients' cell free DNA (cfDNA) contains circulating tumor-derived DNA (ctDNA). The fast dynamic of clearance allows ctDNA to be used as biomarkers for tumor real time profiling. The benefit of non-invasive, cost effective, and easily-repetitive sampling makes liquid biopsy a highly-desirable option for molecular assessment. Deep sequencing has been widely used to investigate subpopulations in complex biological samples. However, there are still limitations of the sequencing technology due to the low yield of cfDNA amount, and errors introduced during sample preparation and sequencing. Approximately 1% of bases are incorrectly identified, depending on the specific platform and sequence context. Although Molecular Identifier can theoretically greatly reduce errors, it suffers from several drawbacks. First, it is difficult to synthesize double strand adapters with randomized Molecular Identifier. Second, due to the difficulty in making high quality Single Molecular Identifier (SMI) adaptors, the ligation efficiency might be compromised and therefore might require large amounts of input DNA. To optimize the liquid biopsy protocol, we first examined if there is any bias in the molecular barcodes' selection during library preparation. Indeed, a skewed trend with molecular barcode selection in ligation process has been detected. We also evaluated the error rates in molecular barcodes and found that there is a substantial amount of errors (~5% of total reads carrying the wrong molecular barcode). To overcome these issues, Omi-seq calculates Digital Molecular Identifier (DMI) using a pool of regular adapters with defined barcodes which can be easily synthesized in high quality. We then analyzed Horizon multiplex I cfDNA reference standard with the lowest available allele frequency (AF) 0.1%. With Omi-error correction, Omi-Seq was able to reproducibly detect the variants. We also evaluated Omi-Seq in real patient samples, Omi-Seq is able to detect variants at AF 0.03%. Omi-Seq was utilized to created cancer profiles for 202 subjects enrolled in The First Affiliated Hospital of Wenzhou Medical University breast cancer study. The gene landscape indicated that the most frequently detected genes are PIK3CA and TP53, followed by ERBB2. The accuracy of Her2 CNV in tissue/FFPE sample is 96% with 85 % sensitivity and 100% specificity. Mutation numbers vary between different molecular subtypes of cfDNA, where the basal-like group had more variants detected than Luminal patients. Furthermore, the ratio changes of max ctDNA AF (ctF) are highly correlated to the clinical response measurement, including cancer relapse, metastatic and treatment resistance. Our data show that ctDNA characterization with Omi-seq could extend the capacity of personalized cancer clinical management. Citation Format: Yinghao Wang, Yaoyao Guan, Jingjing Xiang, Lingguo Kong, Lizhi Lin, Judy Webb, Yunguang Tong, Ouchen Wang. Characterization of breast cancer ctDNA with Omi-Seq [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2489.

A vision-based deep learning approach for the detection and prediction of occupancy heat emissions for demand-driven control solutions

This paper introduces a vision-based deep learning approach that enables the detection and recognition of occupants’ activities within building spaces. The data can feed into building energy management systems through the establishment of occupancy heat emission profiles, which can help minimise unnecessary heating, ventilation, and air-conditioning (HVAC) energy loads and effectively manage indoor conditions. The proposed demand-driven method can enable HVAC systems to adapt and make a timely response to dynamic changes of occupancy, instead of using “static” or fixed occupancy operation schedules, historical load, and time factor. Based on a convolutional neural network, the model was developed to enable occupancy activity detection using a camera. Training data was obtained from online image sources and captured images of various occupant activities in office spaces. Tests were performed by real-time live detection and predictions of occupancy activities in buildings. Initial activities response includes sitting, standing, walking, and napping. Average detection accuracy of 80.62% was achieved. The detection formed the real-time occupancy heat emission profiles known as the Deep Learning Influenced Profile. Along with typical ‘scheduled’ office occupancy profiles, a building energy simulation (BES) tool was used to further assess the framework. An office space in Nottingham, UK was selected to test the proposed method and modelled using building simulation. Using the deep learning detection method, the results showed that the occupancy heat gains could be represented more accurately in comparison to using static office occupancy profiles. The accurate detection of occupants and their activities can also be used to effectively estimate CO2 concentration. The information can be useful for modulating ventilation systems leading to better indoor environmental quality. Overall, this initial approach of the study showed the capabilities of this framework for detecting occupancy activities and providing reliable predictions of building internal gains.

Experimental study on integrated and autonomous conductivity-temperature-depth (CTD) sensor applied for underwater glider

This paper studies a novel CTD sensor (SZQ1-1) which is developed for underwater glider to meet the requirement of autonomous acquisition of high-quality profile hydrodynamic oceanography data. An independently developed electromagnetic induction type conductivity sensor, a quick response thermistor and a high-precision pressure sensor is used to integrate the CTD sensor. Several designs of compact mechanical structure and low-power control acquisition circuit are developed in the CTD sensor. The SZQ1-1 CTD is calibrated with measuring instrument in the laboratory and fourth-degree polynomial fitting equations are developed to fit the curves. After software-based calibration, the SZQ1-1 is compared with SBE 19plus by sea trial. The SZQ1-1 and SBE 19plus were carried by an underwater glider which dived in Northern South China Sea with a maximum depth of 500.36 m. Because the thermal lag error exists in the original data measured with the CTD sensor in the underwater glider, the measured conductivity and salinity data are revised again in the software. According to sea trial results, the real-time temperature, salinity and depth profile data obtained by SZQ1-1 sensor is consistent with the data measured with SBE 19plus.

Real-time metabolic profiling of oesophageal tumours reveals an altered metabolic phenotype to different oxygen tensions and to treatment with Pyrazinib

Oesophageal cancer is the 6th most common cause of cancer related death worldwide. The current standard of care for oesophageal adenocarcinoma (OAC) focuses on neoadjuvant therapy with chemoradiation or chemotherapy, however the 5-year survival rates remain at < 20%. To improve treatment outcomes it is critical to further investigate OAC tumour biology, metabolic phenotype and their metabolic adaptation to different oxygen tensions. In this study, by using human ex-vivo explants we demonstrated using real-time metabolic profiling that OAC tumour biopsies have a significantly higher oxygen consumption rate (OCR), a measure of oxidative phosphorylation compared to extracellular acidification rate (ECAR), a measure of glycolysis (p = 0.0004). Previously, we identified a small molecule compound, pyrazinib which enhanced radiosensitivity in OAC. Pyrazinib significantly inhibited OCR in OAC treatment-naïve biopsies (p = 0.0139). Furthermore, OAC biopsies can significantly adapt their metabolic rate in real-time to their environment. Under hypoxic conditions pyrazinib produced a significant reduction in both OCR (p = 0.0313) and ECAR in OAC treatment-naïve biopsies. The inflammatory secretome profile from OAC treatment-naïve biopsies is heterogeneous. OCR was positively correlated with three secreted factors in the tumour conditioned media: vascular endothelial factor A (VEGF-A), IL-1RA and thymic stromal lymphopoietin (TSLP). Pyrazinib significantly inhibited IL-1β secretion (p = 0.0377) and increased IL-3 (p = 0.0020) and IL-17B (p = 0.0181). Importantly, pyrazinib did not directly alter the expression of dendritic cell maturation markers or reduce T-cell viability or activation markers. We present a new method for profiling the metabolic rate of tumour biopsies in real-time and demonstrate the novel anti-metabolic and anti-inflammatory action of pyrazinib ex-vivo in OAC tumours, supporting previous findings in-vitro whereby pyrazinib significantly enhanced radiosensitivity in OAC.

Dynamics of Biological Processes during Composting of Anaerobically Digested Wastewater Sludge

Microbiological processes occurring in the course of controlled thermophilic composting of dehydrated wastewater sludge anaerobically digested in a reactor at the Lyubertsy waste treatment plant (Moscow, Russia) were studied. Dynamics of the concentrations of nitrogen species in the presence of microorganisms of the nitrogen cycle (ammonifying, nitrifying, denitrifying, and nitrogen-fixing) was studied at the changed temperature modes at sequential stages of long-term composting (98 days). During the active stage of composting, considerable emission of ammonia (553–861 mg m–3) and nitrogen oxide (67–86 mg m–3) were observed on days 6–10; these values significantly exceeded the accepted allowances for atmospheric emissions. Abundance of culturable heterotrophic microorganisms, CFU numbers of nitrogen-fixers, and the presence and activity of cultured nitrifying and denitrifying microorganisms were determined using microbiological techniques. The data of real-time PCR and NGS profiling by the 16S rRNA genes were used to analyze the taxonomic diversity of the microorganisms involved in composting (bacteria, archaea, and fungi); the patterns of succession within the microbial community during this process were established. Laboratory experiments revealed the potential for further decomposition of organic matter of digested sludge, which was probably unavailable to microorganisms under anoxic conditions, but could be degraded by the aerobic microbiota, resulting in a product stimulating plant growth and containing 2.3% of total nitrogen and containing ammonium and nitrate nitrogen (890 and 3750 mg kg–1, respectively).

Examination of the Performance Characteristics of Velostat as an In-Socket Pressure Sensor

Velostat is a low-cost, low-profile electrical bagging material with piezoresistive properties, making it an attractive option for in-socket pressure sensing. The focus of this research was to explore the suitability of a Velostat-based system for providing real-time socket pressure profiles. The prototype system performance was explored through a series of bench tests to determine properties including accuracy, repeatability and hysteresis responses, and through participant testing with a single subject. The fabricated sensors demonstrated mean accuracy errors of 110 kPa and significant cyclical and thermal drift effects of up to 0.00715 V/cycle and leading to up to a 67% difference in voltage range respectively. Despite these errors the system was able to capture data within a prosthetic socket, aligning to expected contact and loading patterns for the socket and amputation type. Distinct pressure maps were obtained for standing and walking tasks displaying loading patterns indicative of posture and gait phase. The system demonstrated utility for assessing contact and movement patterns within a prosthetic socket, potentially useful for improvement of socket fit, in a low cost, low profile and adaptable format. However, Velostat requires significant improvement in its electrical properties before proving suitable for accurate pressure measurement tools in lower limb prosthetics.

Ultrafast real-time observation of double Fano resonances in discrete excitons and single plasmon-continuum

Ultrafast observation of multiple asymmetric Fano line shapes in energetically overlapped single continuum and multiple discrete states is of great theoretical interest in different domains of physics, though their real-time experimental demonstrations are yet to be achieved. Here, we present an experimental observation on time-domain response of the double Fano asymmetries in a metal--two-dimensional semiconductor hybrid prototype at room temperature. The ultrafast interactions in two discrete spin-resolved excitons of ${\mathrm{MoS}}_{2}$ and a single metal plasmon-continuum allow us to observe the generation and evolution of the double Fano line profiles in real time. Apart from the subpicosecond development of double Fano line shapes, we calculate all the time-dependent nonlinear double Fano parameters. These results suggest a better understanding of ultrafast Fano physics in condensed-matter systems and have potential prospects in ultrafast photonic devices using double Fano resonances even at room temperature.