Real-time Control of Solute Plume in Closed Conduit Flow.

The mitigation of accidental toxic chemical releases in a flow system such as a passenger terminal or a tall building is an important study area. The real-time automatic detection and elimination of the chemical cloud is vital to protect human lives against threats. The control of the chemical cloud propagation in the aforementioned flow systems is achieved by forced tributary flow patterns that are produced by distributed boundary actuators such as the ventilation system of the terminal. In the past several decades, studies on the boundary actuators have proved the feasibility of controlling chemical cloud propagation in a channel, at least using numerical simulations. However, the success of a real-time control mechanism depends on whether a control strategy can be determined fast enough to allow its implementation. Due to the intense computational effort associated with solving fluid governing equations, few attempts have been made to demonstrate this flow control problem in real world scenario. This dissertation introduces an approximate but very fast plume control method. A prototype realization of the real-time control system is also demonstrated for controlling a contaminant plume propagation in a circular pipe. A complete flow control system is developed, including a real-time control architecture, based on two novel mathematical models that approximate particle propagation and enable the real-time controllers. Compared to traditional CFD methods, the proposed mathematical models reduce the computational time by more than 99%. The prototype system resembles the major components in the chemical cloud elimination problem. The system includes a camera that monitors the cloud propagation, a boundary port that produces tributary flow pattern, and a computing station that determines the control strategy in real-time. The real-time control architecture consists of a feedforward optimal controller, a feedback controller and a model adaptation process This work elevates the state of the art of real-time flow control to real world scenarios by the success prototype demonstration of real-time flow control. The proposed mathematical models introduce an effective tool to link classical control algorithms with plume control applications. This will ultimately allow the control of a hazardous chemical cloud in critical infrastructure systems.PhDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113479/1/bywang_1.pd

Local Compression in Automated Breast Ultrasound in the Mammographic Geometry

Background, Motivation and Objective: Automated ultrasound scanning (AUS) of the breast has developed more slowly than anticipated. The main limitation, beyond achieving adequate acoustic coupling to the breast, has been excessive shadow artifacts, as reflecting structures at acute angles to the ultrasound beam are not flattened by the transducer as well as in manual scanning. We believe that imaging of the breast in near mammographic compression provides much of the needed flattening. The question under initial study in this effort is, whether in breast AUS under very light mammographic compression, local compression by the transducer might flatten the acutely oriented structures further and reduce the acoustic path length to key structures in the breast. We suspect these improvements will be possible without distorting the breast so dramatically that the lesion registration advantages of scanning the breast in the same system as mammography or digital breast tomosynthesis (DBT) are not realized. Preliminary tests are reported here, as well as design of a system for a more refined human study. Statement of Contribution/Methods: Initial imaging tests were performed in our combined AUS/DBT system. A fiber mesh, loosened slightly in its frame, replaced the standard plastic mammography compression paddle. The transducer, in contact with the mesh and the breast, was translated by motors. The compression force of the linear array transducer on its vertical was manually controlled. Breast phantoms and the breasts of three women were scanned with usual compression by the mesh paddle and then with less global, but added local, compression. Results: Examples of flattened structures were observed more brightly in the locally compressed breasts, and acoustic paths longer than 35 mm were reduced, by _10 mm. In many areas image penetration was 3 cm greater. In one case, image volumes w/wo local compression were spatially aligned by nonlinear image registration software. - - Discussion and Conclusions: Visual indicators of image features expected to provide improved ultrasonic imaging were observed with local compression and lateral movement of tissues appeared acceptable. These results motivated design and construction of an apparatus to make local compression practical and safe. It utilizes joystick control of the vertical compression force during scanning, realized by pneumatic actuators attached to the transducer. The air pressure applied to these actuators is also applied to actuators in the joystick for force feedback to the operator. Two miniature vibrators attached to the joystick provide vibrotactile feedback of the reaction torques computed from the measurements of 6 force sensors on the transducer holder. The fail-safe system design insures no pneumatic compression force application to the breast in case of power loss or emergency shutdown.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87269/4/Saitou50.pd

Successful treatment of dupilumab in Kimura disease independent of IgE: A case report with literature review

Kimura disease (KD) is a rare and benign chronic inflammatory disease of unknown cause. It is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil count, and elevated serum IgE. Currently, no definitive treatments are recommended. A 57-year-old Chinese man was diagnosed with KD after 7 years of slow subcutaneous masses growth. The patient underwent treatment of oral glucocorticoids for 1 year, but the masses recurred as the dosage was tapered down. Subsequent anti-IgE therapy of omalizumab administered subcutaneously at 450 mg/day at a 4-week interval did not show improvement. The size of masses and serum IgE and circulating eosinophils did not decrease significantly after 19 cycles of continuous treatment. Ultimately, switched strategy of dupilumab was applied at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. This treatment demonstrated dramatical effects with reduced masses in each area and fast dropdown of eosinophil counts, while the high level of serum IgE remained without changes. Recently, different biologics including anti-IgE, anti-IL-5, and anti-IL-4/IL-13 have been applied to treat KD with satisfied results and help to explore the pathogenesis of this rare disease. To our knowledge, this is the first report that demonstrates the effects of two different biologics in the same patient and reveals the impressive clinical efficacy of dupilumab to treat KD independent of IgE. Therefore, further investigation of the underlying mechanism and the development of diagnosis and treatment of KD is valuable

Food-specific IgG4-guided diet elimination improves allergy symptoms in children

Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017–1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases

Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance

Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction of miR122 and identified the oxygen-sensing prolyl hydroxylase domain 1 (PHD1) as a miR122 target. Further studies indicated that HIF1α-dependent induction of miR122 participated in a feed-forward pathway for liver protection via the enhancement of hepatic HIF responses through PHD1 repression. Moreover, pharmacologic studies utilizing nanoparticle-mediated miR122 overexpression demonstrated attenuated liver injury. Finally, proof-of-principle studies in patients undergoing orthotopic liver transplantation showed elevated miR122 levels in conjunction with the repression of PHD1 in post-ischemic liver biopsies. Taken together, the present findings provide molecular insight into the functional role of miR122 in enhancing hepatic ischemia tolerance and suggest the potential utility of pharmacologic interventions targeting miR122 to dampen hepatic injury during liver transplantation

The Neurogenic Compound P7C3 Regulates the Aerobic Glycolysis by Targeting Phosphoglycerate Kinase 1 in Glioma

BackgroundP7C3 is a neurogenic compound that exhibits neuroprotective properties in neural cells. However, its target proteins and effects in glioma are unknown.MethodsThe candidate P7C3 target proteins were analyzed using a human protein microarray containing 23136 human proteins. A streptavidin agarose affinity assay was used to verify the direct interaction between P7C3 and phosphoglycerate kinase 1 (PGK1). Mass spectrometry was used to identify the binding sites of PGK1 for P7C3 binding. Seahorse XF96 extracellular flux analyzer was used to measure the cell oxygen consumption rate and extracellular acidification rate. Glycolytic metabolites were measured using the related kits. Protein level was detected by western blotting and immunohistochemical staining. Autophagy was analyzed using a transmission electron microscope and western blotting. The malignancy of tumor progression in vitro and in vivo was analyzed based on cell viability, apoptosis and proliferation, migration and invasion, and xenograft model. Glial cells were marked by antibodies via immunohistochemical staining.ResultsThe human protein microarray identified 577 candidate P7C3 target proteins. The global profile of P7C3 target proteins indicated that P7C3 regulates glycolysis. Metabolic experiments confirmed that P7C3 regulates aerobic glycolysis in glioma cells. The underlying mechanism of P7C3 was found to be direct targeting PGK1 at lysine residues and asparagine residues, and the specific P7C3-PGK1 interaction led to decreased protein level and total intracellular kinase activity of PGK1. The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases indicated that the mRNA level of PGK1 is significantly increased in high-grade glioma, and the abnormally high mRNA level of PGK1 is associated with a poor prognosis in patients with glioma, suggesting that PGK1 is a promising target for glioma therapy. The inhibition of PGK1 and the subsequent suppression of aerobic glycolysis caused by P7C3 inhibited the malignant growth of glioma in vitro and in vivo. Furthermore, P7C3 did not damage normal glial cells under concentration, which exhibit an inhibitory effect on gliomas.ConclusionsThis study revealed that P7C3 suppresses glioma by regulating aerobic glycolysis via directly targeting PGK1. Furthermore, we identified the P7C3 target proteins for the first time which is expected to provide scientific clues for future studies

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwid