Microfluidic Flow Sensing Approaches

Precise flow metrology has an increasing demand in many microfluidic related applications. At the scale and scope of interests, Capillary number instead of Reynold number defines the flow characteristics. The interactions between fluid medium and flow channel surface or the surface tension, cavitation, dissolution, and others play critical roles in microfluidic flow metrology. Conventional flow measurement approaches are not sufficient for solving these issues. This chapter will review the currently available products on the market, their microfluidic flow sensing technologies, the technologies with research and development, the major factors impacting flow metrology, and the prospective sensing approaches for future microfluidic flow sensing

Chicken IFI6 inhibits avian reovirus replication and affects related innate immune signaling pathways

Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-β were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity

Efficacy of Co-administration of Liuwei Dihuang Pills and Ginkgo Biloba Tablets on Albuminuria in Type 2 Diabetes: A 24-Month, Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Purpose: We investigated the effects of Traditional Chinese Medicine (TCM) on the occurrence and progression of albuminuria in patients with type 2 diabetes.Methods: In this randomized, double-blind, multicenter, controlled trial, we enrolled 600 type 2 diabetes without diabetic nephropathy (DN) or with early-stage DN. Patients were randomly assigned (1:1) to receive Liuwei Dihuang Pills (LWDH) (1.5 g daily) and Ginkgo biloba Tablets (24 mg daily) orally or matching placebos for 24 months. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR) from baseline to 24 months.Results: There were 431 patients having UACR data at baseline and 24 months following-up in both groups. Changes of UACR from baseline to follow-up were not affected in both groups: −1.61(−10.24, 7.17) mg/g in the TCM group and −0.73(−7.47, 6.75) mg/g in the control group. For patients with UACR ≥30 mg/g at baseline, LWDH and Ginkgo biloba significantly reduced the UACR value at 24 months [46.21(34.96, 58.96) vs. 20.78(9.62, 38.85), P < 0.05]. Moreover, the change of UACR from baseline to follow-up in the TCM group was significant higher than that in the control group [−25.50(−42.30, −9.56] vs. −20.61(−36.79, 4.31), P < 0.05].Conclusion: LWDH and Ginkgo biloba may attenuate deterioration of albuminuria in type 2 diabetes patients. These results suggest that TCM is a promising option of renoprotective agents for early stage of DN.Trial registration: The study was registered in the Chinese Clinical Trial Registry. (no. ChiCTR-TRC-07000037, chictr.org

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Micromachined Thermal Time-of-Flight Flow Sensors and Their Applications

Micromachined thermal flow sensors on the market are primarily manufactured with the calorimetric sensing principle. The success has been in limited industries such as automotive, medical, and gas process control. Applications in some emerging and abrupt applications are hindered due to technical challenges. This paper reviews the current progress with micromachined devices based on the less popular thermal time-of-flight sensing technology: its theory, design of the micromachining process, control schemes, and applications. Thermal time-of-flight sensing could effectively solve some key technical hurdles that the calorimetric sensing approach has. It also offers fluidic property-independent data acquisition, multiparameter measurement, and the possibility for self-calibration. This technology may have a significant perspective on future development

Ball Screw Fault Diagnosis Based on Wavelet Convolution Transfer Learning

The ball screw is the core component of the CNC machine tool feed system, and its health plays an important role in the feed system and even in the entire CNC machine tool. This paper studies the fault diagnosis and health assessment of ball screws. Aiming at the problem that the ball screw signal is weak and susceptible to interference, using a wavelet convolution structure to improve the network can improve the mining ability of signal time domain and frequency domain features; aiming at the challenge of ball screw sensor installation position limitation, a transfer learning method is proposed, which adopts the domain adaptation method as jointly distributed adaptation (JDA), and realizes the transfer diagnosis across measurement positions by extracting the diagnosis knowledge of different positions of the ball screw. In this paper, the adaptive batch normalization algorithm (AdaBN) is introduced to enhance the proposed model so as to improve the accuracy of migration diagnosis. Experiments were carried out using a self-made lead screw fatigue test bench. Through experimental verification, the method proposed in this paper can extract effective fault diagnosis knowledge. By collecting data under different working conditions at the bearing seat of the ball screw, the fault diagnosis knowledge is extracted and used to identify and diagnose the position fault of the nut seat. In this paper, some background noise is added to the collected data to test the robustness of the proposed network model

Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats

Context: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). Objective: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis factor-α converting enzyme) signalling and investigated its anti-DN (diabetic nephropathy) effects in a DN rat model. Materials and methods: In vitro, cells were treated with 200 μg/mL advanced glycation end products (AGEs), and then co-cultured with 20 μg/mL TFA for 24 h. Real time PCR, western blotting and co-immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5 mg/kg/d) was used as a positive control. Results: IC50 of TFA is 35.6 μM in HK2 and 39.6 μM in HRMC. TFA treatment (20 μM) inhibited the activation of iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and ED50=67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the expression of proinflammatory cytokines and exerted anti-inflammatory effects significantly though inhibiting the activation of iRhom2/TACE signalling. Discussion and conclusions: Our results show that TFA could dose-dependently ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE signalling and attenuating ER stress. These results suggest that TFA has potential therapeutic value for the treatment of DN in humans

Responses of growing‐season soil respiration to water and nitrogen addition as affected by grazing intensity

1. Most grasslands in the world, including the semi-arid steppe in China, are threatened by nitrogen deposition, precipitation change and livestock grazing, which greatly affect soil carbon processes (e.g. soil respiration). Although the individual effects of nitrogen deposition and precipitation change on soil respiration are well understood, how their effects on soil respiration are altered by different grazing intensities is unclear. 2. To determine how the effects of nitrogen deposition and precipitation change on soil respiration are affected by grazing intensity, we conducted an experiment in a semi-arid steppe involving areas that experienced 10 years of no, light, moderate or heavy grazing. These areas were treated with water addition (110 mm, 30% of the mean annual precipitation) and nitrogen addition (10.5 g m(-2) year(-1)). 3. Our results showed that relative to no grazing, grazing decreased growing-season soil respiration by 10%-19%. The decline in soil respiration was mainly via its negative effects on above-ground net primary productivity (ANPP) and the fungi: bacteria ratio with light grazing, mainly via its negative effects on ANPP and leaf nitrogen content with moderate grazing, and mainly via its negative effects on ANPP, root biomass, microbial biomass and the fungi: bacteria ratio with heavy grazing. 4. Across all grazing intensities, both water and water+nitrogen addition increased growing-season soil respiration, whereas nitrogen addition decreased growing-season soil respiration. Water addition increased growing-season soil respiration mostly via its positive effect on ANPP with no grazing and with low grazing, and mostly via its positive effects on both plant and microbial variables with moderate and heavy grazing. The pathways determining the nitrogen addition-induced decline in growing-season soil respiration were the same within each of the four levels of grazing and mostly resulted from its negative effect on microbial variables. 5. Our results indicate that the effects of climate change on growing-season soil respiration and other soil carbon processes in grasslands depend on grazing intensity. The findings suggest that grazing intensity should be considered in future manipulation experiments and should be included in carbon models to accurately simulate soil carbon dynamics under scenarios of climate change in grassland ecosystems