Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Gyrotactic microorganisms bioconvection in combined convective magnetohydrodynamic Casson nanofluid flow over a vertically surfaced saturated porous media with variable viscosity

The current article focuses on mass and thermal transfer analysis of a two-dimensional immovable combined convective nanofluid flow including motile microorganisms with temperature-dependent viscosity on top of a vertical plate through a porous medium, and a model has been developed to visualize the velocity slip impacts on a nonlinear partial symbiotic flow. The governed equations include all of the above physical conditions, and suitable nondimensional transfigurations are utilized to transfer the governed conservative equations to a nonlinear system of differential equations and obtain numerical solutions by using the Shooting method. Numerical studies have been focusing on the effects of intricate dimensionless parameters, namely, the Casson fluid parameter, Brownian motion parameter, thermophoresis parameter, Peclet number, bioconvection parameter, and Rayleigh number, which have all been studied on various profiles such as momentum, thermal, concentration, and density of microorganisms. The concentration boundary layer thickness and density of microorganisms increased as the Casson fluid parameter, Brownian and thermophoresis parameters increased, whereas the bioconvection parameter, Peclet number, and Rayleigh number increased. The thermal boundary layer thickness, concentration boundary layer thickness, and density of microorganisms all decreased. The velocity distribution decreases as the Peclet number, bioconvection, and thermophoresis parameters rise but rises as the Rayleigh number, Brownian motion parameter, and Casson fluid parameter rise. These are graphed via plots along with divergent fluid parameters.     

Estimates of daily oxygen consumption,carbon dioxide and methane emissions,and heat production for beef and dairy cattle using spot gas sampling

A simulation study was conducted to examine accuracy of estimating daily O₂ consumption, CO₂ and CH₄ emissions, and heat production (HP) using a spot sampling technique and to determine optimal spot sampling frequency (FQ). Data were obtained from 3 experiments where daily O₂ consumption, emissions of CO₂ and CH₄, and HP were measured using indirect calorimetry (respiration chamber or headbox system). Experiment 1 used 8 beef heifers (ad libitum feeding; gaseous exchanges measured every 30 min over 3 d in respiration chambers); Experiment 2 used 56 lactating Holstein-Friesian cows (restricted feeding; gaseous exchanges measured every 12 min over 3 d in respiration chambers); Experiment 3 used 12 lactating Jersey cows (ad libitum feeding; gaseous exchanges measured every hour for 1 d using headbox style chambers). Within experiment, averages of all measurements (FQALL) and averages of measurements selected at time points with 12, 8, 6, or 4 spot sampling FQ (i.e., sampling every 2, 3, 4, and 6 h in a 24-h cycle, respectively; FQ12, FQ8, FQ6, and FQ4, respectively) were compared. Within study a mixed model was used to compare gaseous exchanges and HP among FQALL, FQ12, FQ8, FQ6, and FQ4, and an interaction of dietary treatment by FQ was examined. A regression model was used to evaluate accuracy of spot sampling within study [i.e., FQALL (observed) vs. FQ12, FQ8, FQ6, or FQ4 (estimated)]. No interaction of diet by FQ was observed for any variables except for CH₄ production in experiment 1. No FQ effect was observed for gaseous exchanges and HP except in experiment 2 where CO₂ production was less (5,411 vs. 5,563 L/d) for FQ4 compared with FQALL, FQ12, and FQ8. A regression analysis between FQALL and each FQ within study showed that slopes and intercepts became farther from 1 and 0, respectively, for almost all variables as FQ decreased. Most variables for FQ12 and FQ8 had root mean square prediction error (RMSPE) less than 10% of the mean and concordance correlation coefficient (CCC) greater than 0.80, and RMSPE increased and CCC decreased as FQ decreased. When a regression analysis was conducted with combined data from the 3 experiments (mixed model with study as a random effect), results agreed with those from the analysis for the individual studies. Prediction errors increased and CCC decreased as FQ decreased. Generally, all the estimates from FQ12, FQ8, FQ6, and FQ4 had RMSPE less than 10% of the means and CCC greater than 0.90 except for FQ6 and FQ4 for O₂ consumption and CH₄ production. In conclusion, the spot sampling simulation with 3 indirect calorimetry experiments indicated that FQ of at least 8 samples (every 3 h in a 24-h cycle) was required to estimate daily O₂ consumption, CO₂ and CH₄ production, and HP and to detect changes in those in response to dietary treatments. This sampling FQ may be considered when using techniques that measure spot gas exchanges such as the GreenFeed and face mask systems.     

用于厚屏蔽小探测器的蒙特卡罗模拟减方差方法研究

反应堆屏蔽计算中经常出现厚屏蔽、小探测器问题，常规蒙特卡罗方法难以有效解决。基于自动重要抽样（AIS）方法，本文提出了小探测器自动重要抽样(SDAIS)方法，并针对小探测器问题，优化了AIS方法的虚粒子赌分裂算法。该方法在自主开发的蒙特卡罗屏蔽程序MCShield上进行了实现。使用NUREG/CR-6115 PWR基准题验证该方法的正确性和计算效率。结果表明，SDAIS方法可有效地解决厚屏蔽小探测器问题，相比AIS方法及传统的重要性方法，计算效率提升1~2个量级。     

An automated patient monitoring using discrete‐time wireless sensor networks

In recent years, Internet of Things (IoT) devices are used for remote health monitoring. For remotely monitoring a patient, only the health information at different time points are not sufficient; predicted values of biomarkers (for some future time points) are also important. In this article, we propose a powerful statistical model for an efficient dynamic patient monitoring using wireless sensor nodes through Bayesian Learning (BL). We consider the setting where a set of correlated biomarkers are measured from a patient through wireless sensors, but the sensors only report the ordinal outcomes (say, good, fair, high, or very high) to the sink based on some prefixed thresholds. The challenge is to use the ordinal outcomes for monitoring and predicting the health status of the patient under consideration. We propose a linear mixed model where interbiomarker correlations and intrabiomarker dependence are modeled simultaneously. The estimated and the predicted values of the biomarkers are transferred over the internet so that health care providers and the family members of the patient can remotely monitor the patient. Extensive simulation studies are performed to assess practical usefulness of our proposed joint model, and the performance of the proposed joint model is compared to that of some other traditional models used in the literature.     

Simultaneous synthesis of a heat exchanger network with multiple utilities using utility substages

Heat exchanger network synthesis (HENS) has progressed by using mathematical programming-based simultaneous methodology. Although various considerations such as non-isothermal mixing and bypass streams are applied to consider real world alternatives in modeling phase, many challenges are faced because of its properties within non-convex mixed-integer nonlinear programming (MINLP). We propose a modified superstructure, which contains a utility substage for use in considering multiple utilities in a simultaneous MINLP model. To improve model size and convergence, fixed utility locations according to temperature and series connections between utilities are suggested. The numbers of constraints, discrete, and continuous variables show that overall model size decreases compared with previous research. Thus, it is possible to expand the feasible search area for reaching the nearest global solution. The model's effectiveness and applications are exemplified by several literature problems, where it is used to deduce a network superior to that of any other reported methodology.     

Household endotoxin reduction in the Louisa Environmental Intervention Project for rural childhood asthma

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic school children (N = 104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5-14 years) were recruited and block-randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow-up visits. Mixed-model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post-intervention visits. The extensive compared with the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29-0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post-intervention by residents.     

Spray coating process variable and property analysis of UV-curable polyurethane acrylate coating on polycarbonate substrate

A series of spray coating experiments were conducted on an UV-curable, polyurethane-modified, acrylate-based coating formulation with the aim to control defects, coating thickness, and thickness variation. Statistical approaches including design of experiment, residual examination, analysis of variance, and t-test were used in designing the experiments and analyzing data. Viscosity of formulation, atomizing pressure, liquid feeding pressure, distance between nozzle and substrate, and travel speed of substrate were the process variables studied. The ranges of process variables that gave defect-free coating were identified and used in the subsequent experiments to determine process variables and interactions that had significant contribution to the changes in coating thickness and thickness variation. All process variables studied were found to have contribution to the change in coating thickness, but they showed no significant contribution to the variation of coating thickness. No interaction displayed significant contribution. Confirmation tests performed on extra samples prepared with varying coating thicknesses indicated a good agreement with the experimental results. Additional samples were tested for total transmittance, transmission haze, adhesion, surface roughness, hardness, scratch hardness, abrasion resistance, and durability to attack of car wash chemicals. Spray coated samples showed slight improvement in the total transmittance over the uncoated samples, while maintaining the transmission haze and exhibiting rougher surfaces. Only samples with thin coatings were found to possess sufficient adhesion to the substrate. These thin coatings gave improved hardness, scratch hardness, and durability to car wash attack to the level comparable to commercial coated polycarbonate headlamp lenses, whilst giving better abrasion resistance.     

A case-deletion diagnostic for penalized calibration estimators and BLUP under linear mixed models in survey sampling

The penalized calibration technique in survey sampling combines usual calibration and soft calibration by introducing a penalty term. Certain relevant estimates in survey sampling can be considered as penalized calibration estimates obtained as particular cases from an optimization problem with a common basic structure. In this framework, a case deletion diagnostic is proposed for a class of penalized calibration estimators including both design-based and model-based estimators. The diagnostic compares finite population parameter estimates and can be calculated from quantities related to the full data set. The resulting diagnostic is a function of the residual and leverage, as other diagnostics in regression models, and of the calibration weight, a singular feature in survey sampling. Moreover, a particular case, which includes the basic unit level model for small area estimation, is considered. Both a real and an artificial example are included to illustrate the diagnostic proposed. The results obtained clearly show that the proposed diagnostic depends on the calibration and soft-calibration variables, on the penalization term, as well as on the parameter to estimate.     

Gradient-based recursive parameter estimation for a periodically nonuniformly sampled-data Hammerstein–Wiener system based on the key-term separation

The identification of the Hammerstein–Wiener (H-W) systems based on the nonuniform input–output dataset remains a challenging problem. This article studies the identification problem of a periodically nonuniformly sampled-data H-W system. In addition, the product terms of the parameters in the H-W system are inevitable. In order to solve the problem, the key-term separation is applied and two algorithms are proposed. One is the key-term-based forgetting factor stochastic gradient (KT-FFSG) algorithm based on the gradient search. The other is the key-term-based hierarchical forgetting factor stochastic gradient (KT-HFFSG) algorithm. Compared with the KT-FFSG algorithm, the KT-HFFSG algorithm gives more accurate estimates. The simulation results indicate that the proposed algorithms are effective.