Localized surface functionalization with atmospheric-pressure microplasma jet for cell-on-a-chip applications

Surface properties of biopolymers are crucial for providing topographical and chemical cues to affect cellular behaviors, such as attachment, spreading, viability, proliferation, and differentiation. As an effective surface modification technique, plasma treatment is often applied to enhance surface wettability, adhesion, and biocompatibility of polymers. This study concentrates on developing technical platforms, experimental procedures, and computational-statistical models to manipulate and control the cellular functions on specifically modified polymer surfaces. A novel freeform microplasma-generated maskless surface patterning process was developed to create spatially defined topological and chemical features on biopolymer surface. Global and localized plasma functionalization was performed on polycaprolactone (PCL) samples to introduce biophysical, biochemical, biological and structural cues to enhance cellular response including attachment, proliferation and differentiation. A plasma computational-statistical model was developed to predict the changes in biopolymer surface physicochemical properties following the oxygen based plasma surface functionalization. Furthermore, an integrated system including localized plasma functionalization was specifically designed for the development of biologically inspired devices. The capabilities, benefits, and challenges of the integrated multifunctional biofabrication system to develop cell-on-a-chip device were also illustrated. The objective of this thesis is to contribute scientific and engineering knowledge to the utilization of plasma chemistry to enhance surface functionalization, development of an engineering model for local plasma treatment, and integration of biofabrication processes to assemble cell-on-a-chip devices.Ph.D., Mechanical Engineering and Mechanics -- Drexel University, 201

Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling.

Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings

Effect of Liuweibuqi capsule, a Chinese patent medicine, on the JAK1/STAT3 pathway and MMP9/TIMP1 in a chronic obstructive pulmonary disease rat model

AbstractObjectiveTo observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine (TCM), on the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and matrix metalloproteinases (MMPs) in a chronic obstructive pulmonary disease (COPD) rat model with lung deficiency in terms of TCM's pattern differentiation.MethodsRats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group (n= 10). Aside from the normal group, all rats were exposed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency. Models were established after 28 days and then the normal and model groups were given normal saline (0.09 g/kg), Liuweibuqi group was given Liuweibuqi capsule (0.35 g/kg), Jinshuibao group was given Jinshuibao capsules (0.495 g/kg), and the spleen group was given spleen aminopeptidase (0.33 mg/kg), once a day for 30 days. Changes in symptoms, signs, and lung histology were observed. Lung function was measured with a spirometer. Serum cytokines were detected using enzyme-linked immunosorbent assay, and changes in the JAK/STAT pathway, MMP-9, and MMPs inhibitor 1 (TIMP1) were detected by immunohistochemistry, RT-PCR, and western blotting, respectively.ResultsCompared with the normal group, lung tissue was damaged, and lung function was reduced in the model control group. Additionally, the levels of interleukin (IL)-1β, γ interferon (IFN-γ), and IL-6 were higher, while IL-4 and IL-10 were lower in the model control group than those in the normal group. The expressions of JAK1, STAT3, p-STAT3, and MMP-9 mRNA and protein in lung tissue were higher, and TIMP1 mRNA and protein was lower in the model group compared with the normal group. After treatment, compared with the model group, the expression of inflammatory cytokines was lower in each treatment group, and expressions of JAK/STAT pathway, MMPs were lower. Compared with the positive control groups, the Jinshuibao and spleen aminopeptidase groups, lung function was better, and JAK1, STAT3, and p-STAT3 protein were lower and TIMP1 was higher in the Liuweibuqi group.ConclusionLiuweibuqi capsules can improve the symptoms of COPD possibly by regulating the expression of the JAK1/STAT3 pathway and MMP9/TIMP1

The influence of facial femininity on Chinese and White UK women's jealousy

It is well established that men report greater jealousy when imagining scenarios in which their romantic partner interacts with men displaying masculine physical characteristics. However, few studies have tested for corresponding effects of sexually dimorphic characteristics on women’s jealousy or tested for these effects in non-Western samples. Thus, we investigated the effects of experimentally manipulated sexually dimorphic face-shape cues on Chinese and White UK women’s jealousy perceptions. Chinese and White UK women both reported greater jealousy when imagining scenarios in which their romantic partner interacted with more feminine women. Both groups of women showed large effects of facial femininity on jealousy perceptions for both Chinese and White UK stimuli. Together, these results suggest that sexually dimorphic facial characteristics influence women’s jealousy and that this effect is not unique to women raised in Western cultures

Adaptive Environment Modeling Based Reinforcement Learning for Collision Avoidance in Complex Scenes

The major challenges of collision avoidance for robot navigation in crowded scenes lie in accurate environment modeling, fast perceptions, and trustworthy motion planning policies. This paper presents a novel adaptive environment model based collision avoidance reinforcement learning (i.e., AEMCARL) framework for an unmanned robot to achieve collision-free motions in challenging navigation scenarios. The novelty of this work is threefold: (1) developing a hierarchical network of gated-recurrent-unit (GRU) for environment modeling; (2) developing an adaptive perception mechanism with an attention module; (3) developing an adaptive reward function for the reinforcement learning (RL) framework to jointly train the environment model, perception function and motion planning policy. The proposed method is tested with the Gym-Gazebo simulator and a group of robots (Husky and Turtlebot) under various crowded scenes. Both simulation and experimental results have demonstrated the superior performance of the proposed method over baseline methods.Comment: accepted by IROS202

A Thermoplastic Elastomer Belt Based Robotic Gripper

Novel robotic grippers have captured increasing interests recently because of their abilities to adapt to varieties of circumstances and their powerful functionalities. Differing from traditional gripper with mechanical components-made fingers, novel robotic grippers are typically made of novel structures and materials, using a novel manufacturing process. In this paper, a novel robotic gripper with external frame and internal thermoplastic elastomer belt-made net is proposed. The gripper grasps objects using the friction between the net and objects. It has the ability of adaptive gripping through flexible contact surface. Stress simulation has been used to explore the regularity between the normal stress on the net and the deformation of the net. Experiments are conducted on a variety of objects to measure the force needed to reliably grip and hold the object. Test results show that the gripper can successfully grip objects with varying shape, dimensions, and textures. It is promising that the gripper can be used for grasping fragile objects in the industry or out in the field, and also grasping the marine organisms without hurting them

PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene expression

Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8 are associated with X-linked mental retardation. It usually functions as a transcriptional co-activator by associating with H3K4me3 and RNA polymerase II. We found that PHF8 may associate with another regulator, REST/NRSF, predominately at promoter regions via studying several published PHF8 chromatin immunoprecipitation-sequencing (ChIP-Seq) datasets. Our analysis suggested that PHF8 not only activates but may also repress gene expression

New evidence for the effect of type 2 diabetes and glycemic traits on testosterone levels: a two-sample Mendelian randomization study

ObjectiveType 2 diabetes mellitus (T2DM) is an endocrine-related disease with an increasing incidence worldwide. Male sexual dysfunction is common in diabetic patients. Therefore, we designed a Mendelian randomization (MR) study to investigate the association of type 2 diabetes and 3 glycemic traits with testosterone levels.MethodsUncorrelated single nucleotide polymorphisms (SNPs) associated with T2DM (N = 228), fasting insulin (N = 38), fasting glucose (N = 71), and HbA1c (N = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with testosterone levels (total testosterone, TT, bioavailable testosterone, BT, and sex hormone-binding globulin, SHBG) were obtained from the UK Biobank studies and other large consortia. Two-sample MR analysis was used to minimize the bias caused by confounding factors and response causality. Multivariable MR analysis was performed using Body mass index (BMI), Triglycerides (TG), LDL cholesterol (LDL), and adiponectin to adjust for the effects of potential confounders.ResultsType 2 diabetes mellitus was associated with the decrease of total testosterone (β: -0.021,95%CI: -0.032, -0.010, p<0.001) and sex hormone binding globulin (β: -0.048,95%CI: -0.065, -0.031, p<0.001). In males, total testosterone (β: 0.058, 95% CI: 0.088, 0.028, p < 0.001) decreased. In females, it was associated with an increase in bioavailable testosterone (β: 0.077,95%CI: 0.058,0.096, p<0.001). Each unit (pmol/L) increase in fasting insulin was associated with 0.283nmol/L decrease in sex hormone-binding globulin (95%CI: -0.464, -0.102, p=0.002) and 0.260nmol/L increase in bioavailable testosterone (95%CI: -0.464, -0.102, p= 0.002). In males, sex hormone binding globulin decreased by 0.507nmol/L (95%CI: -0.960, -0.054, p= 0.028) and bioavailable testosterone increased by 0.216nmol/L (95%CI: 0.087,0.344, p= 0.001). In females, sex hormone binding globulin decreased by 0.714 nmol/L (95%CI: -1.093, -0.335, p<0.001) and bioavailable testosterone increased by 0.467nmol/L (95%CI: 0.286,0.648, p<0.001). Each unit (%) increase in HbA1c was associated with 0.060nmol/L decrease in sex hormone-binding globulin (95%CI: -0.113, -0.007, p= 0.026). In males, total testosterone decreased by 0.171nmol/L (95%CI: -0.288, -0.053, p=0.005) and sex hormone binding globulin decreased by 0.206nmol/L (95%CI: -0.340, -0.072, p=0.003). Total testosterone increased by 0.122nmol/L (95%CI: 0.012,0.233, p=0.029) and bioavailable testosterone increased by 0.163nmol/L (95%CI: 0.042,0.285, p=0.008) in females.ConclusionsUsing MR Analysis, we found independent effects of type 2 diabetes, fasting insulin, and HbA1c on total testosterone and sex hormone-binding globulin after maximum exclusion of the effects of obesity, BMI, TG, LDL and Adiponectin

Efficient strategies for constrained black-box optimization by intrinsically linear approximation (CBOILA)

In this paper, a novel trust-region-based surrogate-assisted optimization method, called CBOILA (Constrained Black-box Optimization by Intrinsically Linear Approximation), has been proposed to reduce the number of black-box function evaluations and enhance the efficient performance for solving complex optimization problems. This developed optimization approach utilizes an assembly of intrinsically linear approximations to seek the optimum with incorporation of three strategies: (1) extended-box selection strategy (EBS), (2) global intelligence selection strategy (GIS) and (3) balanced trust-region strategy. EBS aims at reducing the number of function evaluations in current iteration by selecting points close to the given trust region boundary. Whilst, GIS is designed to improve the exploration performance by adaptively choosing points outside the trust region. The balanced trust-region strategy works with four indicators, which will be triggered by the quality of the approximation, the movement direction of the search, the location of the sub-optimum, and the condition of the termination, respectively. By modifying the move limit of each dimension accordingly, CBOILA is capable of attaining a balanced search between exploitation and exploration for the optimal solutions. To demonstrate the potentials of the proposed optimization method, four widely used benchmark problems have been examined and the results have also been compared with solutions by other metamodel-based algorithms in published works. Results show that the proposed method can efficiently and robustly solve constrained black-box optimization problems within an acceptable computational time