Continuous Microfluidic Viscometers for Biochemical and Diagnostic Analysis

Microfluidic technologies have advanced rapidly over the past two decades. Numerous microfluidic devices to assess different biomarkers have been reported, yet very few address physical properties, such as viscosities, of biological specimens. Continuous monitoring of viscosity changes provides a new biological and diagnostic parameter not yet made readily accessible due to the low obtainable volume of many biological specimens. In this dissertation, we have developed a droplet-based, water-in-oil continuous viscometer capable of measuring viscosity changes in 10 seconds or less and consuming a total sample volume of less than 1 microliter per hour. The viscometer employs a flow-focusing geometry and generates droplets under constant pressure. The length of the droplets is highly correlated to the aqueous-phase viscosity at high ratios of aqueous-to-oil inlet pressure, resulting in a linear calibration relationship for viscosity measurements. Theoretical analysis verifies the linear relationship and guides viscometer optimization. The viscometer can be used for Newtonian fluids and, by accurately calculating shear rates, for non-Newtonian fluids. The shear rates can be adjusted experimentally by varying the input pressures. The viscometer measures viscosities reliably over three orders of magnitude with less than 5% error. Using the viscometer, we measured viscosity changes of whole blood during blood coagulation continuously under different conditions. We have also developed a particle-based microviscometer for label-free DNA detection by applying the asynchronous magnetic bead rotation (AMBR) phenomenon. We have demonstrated experimentally that the rotation period of paramagnetic beads is linearly proportional to the viscosity of a DNA solution surrounding the paramagnetic beads, as expected theoretically. Simple optical measurement of asynchronous microbead motion determines solution viscosity precisely in microscale volumes, thus allowing an estimate of DNA concentration or average fragment length. The effects of different operating conditions have been investigated and a standard deviation of less than 10% has been achieved for viscosity measurements under the optimal conditions. The response of the AMBR viscometer yields reproducible measurement of DNA solutions, enzymatic digestion reactions, and PCR systems at template concentrations across a 5000-fold range. Preliminary design and operation of a ChessTrap device has been demonstrated to trap single particles into individual chambers for viscometer automation.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137145/1/yunzili_1.pd

Inhibition of HSP90 promotes neural stem cell survival from oxidative stress through attenuating NF-κB/p65 activation

Stem cell survival post transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades of yeas. The engrafted stem cells face the damage of oxidative stress, inflammation and immune response at the lesion point in host. Among the pathology, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in detail mechanism of stem cell survival from oxidative stress has not revealed clearly. Here in this study, we used hydrogen peroxide (H2O2) to induced the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors respectively targeting at each signalling indicated an upper streaming role of HSP90 upon NF-κB/p65 on NSCs survival. Pre-inhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress, and also promotes the stem cell application on CNS pathologies

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF- κ

Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies

Inhibition of HSP90 promotes neural stem cell survival from oxidative stress through attenuating NF-κB/p65 activation

Stem cell survival post transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades of yeas. The engrafted stem cells face the damage of oxidative stress, inflammation and immune response at the lesion point in host. Among the pathology, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in detail mechanism of stem cell survival from oxidative stress has not revealed clearly. Here in this study, we used hydrogen peroxide (H2O2) to induced the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors respectively targeting at each signalling indicated an upper streaming role of HSP90 upon NF-κB/p65 on NSCs survival. Pre-inhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress, and also promotes the stem cell application on CNS pathologies

Changes in myelinated fibers in the hippocampus of streptozotocin-induced diabetic rats: a stereological investigation

Diabetes causes cognitive impairment, and the hippocampus is important for long-term and permanent memory function. However, the mechanism of their interaction is still unclear. In this study, rat models of diabetes mellitus were generated by a single injection of streptozotocin (STZ). This study aims to explore the changes in myelinated fibers in the hippocampus of type 1 diabetic rats. The unbiased stereological methods and transmission electron microscopy were used to obtain the total volume of the hippocampus, the total volume of the myelin sheath, the total length of the myelinated nerve fibers, the distribution of the length with different diameters of the myelinated fibers, and the distribution of the length with different thickness of the myelin sheath. Stereological analysis revealed that, compared to that of the control group, the total myelinated fibers volumes and the total myelinated fibers length were decreased slightly, while the total volume and the thickness of myelin sheaths were significantly decreased in the diabetic group. Finally, when compared with the control group, the total length of myelinated fibers in the diabetes group was significantly reduced, with diameters ranging from 0.7 to 1.1 μm and thicknesses of myelin sheaths from 0.15 to 0.17 μm. This study provides the first experimental evidence by stereological means to demonstrate that myelinated nerve fibers may be the key factor in cognitive dysfunction in diabetes

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (D500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-beta levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-beta responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.Peer reviewe

Asynchronous Magnetic Bead Rotation (AMBR) Microviscometer for Label-Free DNA Analysis

We have developed a label-free viscosity-based DNA detection system, using paramagnetic beads as an asynchronous magnetic bead rotation (AMBR) microviscometer. We have demonstrated experimentally that the bead rotation period is linearly proportional to the viscosity of a DNA solution surrounding the paramagnetic bead, as expected theoretically. Simple optical measurement of asynchronous microbead motion determines solution viscosity precisely in microscale volumes, thus allowing an estimate of DNA concentration or average fragment length. The response of the AMBR microviscometer yields reproducible measurement of DNA solutions, enzymatic digestion reactions, and PCR systems at template concentrations across a 5000-fold range. The results demonstrate the feasibility of viscosity-based DNA detection using AMBR in microscale aqueous volumes

Rainbow Dance, Inkling of Collapse or Symbol of Eternal Love

“The Dance of Rainbow Skirts” ( Wu nishang 舞霓裳) figures prominently in two Chinese traditional plays Rain on the Wutong Tree and The Palace of Eternal Youth, both focusing on the love story between the Tang Emperor Xuanzong and Lady Yang. In these two plays, dance not only serves as a symbol for Emperor Tang Xuanzong and Lady Yang Guifei’s love, but also links the earthly realm and the immortal world. Comparing the two works, this paper explores how the art of dance comes into play in the love between Emperor Tang Xuanzong and Lady Yang Guifei, and examines the ways in which dance connects to the different interpretations of their love. The paper argues that dance is an inkling of collapse and symbol of eternal love in the two plays respectively. In the former play Lady Yang’s dance portrays her beauty and Emperor Xuanzong’s affection, but the beautiful image of her only lives on in Xuanzong’s dream after the rebellion. The paradox of “fu” (福，happiness) and “huo” (祸，disaster) is well presented in dance. In contrast, in the later play the Rainbow Dance helps to portray Lady Yang as a talented subject and symbolizes her eternal love with Emperor Xuanzong. By traveling to the palace of the moon in her dreams, transcribing the music and performing the dance, Lady Yang takes control of her fate, art and love

“Home Sweet Home”: Displacement and Belonging in Post-1960s Diasporic Chinese Literature

Situated at the intersection of Sinophone and Diaspora Studies and focusing on the rhetoric of “home,” my dissertation explores the ways in which Chinese immigrant Sinophone writers and Anglophone writers in the U.S. construct “imaginative homes” in response to the absence of their physical homes. Through detailed analysis of works by Yu Lihua (Again the Palm Trees, 1967), Yan Geling (The Criminal Lu Yanshi, 2011; A Woman’s Epic, 2006), Pai Hsien-yung (Taipei People, 1971), Shi Yu (New York Lover, 2004), Chen Qian (Listen to the Caged Bird Sing, 2010), Rong Rong (Notes of a Couple, 2004) and Ha Jin (A Free Life, 2007; A Map of Betrayal, 2014), I explore the shifting dynamics of roots and routes by examining how Chinese diasporic subjects formulate their identities in negotiations between their homeland and the adopted land. Far from being an either/or binary, Chinese diasporic subjects often experience home and homelessness, uprooting and re-rooting simultaneously. This dissertation also delineates that, from a historical perspective, diasporic Chinese’s experience of home has shifted from being nationally affiliated in 1960s–70s overseas Chinese student writings to being personally oriented in post-1980s Chinese immigrant writings. This study of “home” in diasporic Chinese writings bridges Chinese diaspora and Sinophone studies, and further highlights the heterogeneity and complexity of the notion of “home