Doctor of Philosophy

dissertationIn microsurgical operating room environments, it is often necessary to cut and reattach vessels multiple times during surgery. The current method of vascular anastomosis is hand suturing. This technique is time consuming, difficult, and requires complex instruments. To solve this problem, researchers have explored alternative ways to improve this technique. Typical examples are staples, clips, cuffing rings, adhesives, and laser welding. The potential of these techniques has been hindered due to the lack of biocompatibility, complex procedures for use, and general inefficiency. As a result, few of these devices have been commercialized. One promising alternative is a ring-pin coupling device. This device has been shown to be useful for venous anastomosis, but lacks the versatility necessary for arterial applications. One purpose of this study was to optimize a vascular coupling design that could be used for arteries and veins of various sizes. To achieve this, finite element analysis was used to simulate the vessel-device interaction during anastomosis. Parametric simulations were performed to optimize the number of pins, the wing pivot point, and the pin offset of the design. The interaction of the coupler with various blood vessel sizes was also evaluated. The optimal vascular coupling device has four rotatable wings and one translatable spike in each wing. Prototypes were manufactured using polytetrafluoroethylene (PTFE) and high-density polyethylene (HDPE). A set of installation tools was designed to facilitate the anastomosis process. Proof-of-concept testing with the vascular coupler using plastic tubes and porcine cadaver vessels showed that the coupler could be efficiently attached to blood vessels, did not leak after the anastomosis was performed, had sufficient joint strength, and had little impact on flow in the vessel. A simplified finite element model assisted in the evaluation of the tearing likelihood of human vessels during installation of the coupler. The entire anastomosis process can be completed in three minutes when using the vascular coupler to join porcine cadaver vessels. A metal-free vascular coupling system that can be used for both arteries and veins was designed, fabricated, and tested. A set of corresponding instruments were developed to facilitate the anastomosis process. Evaluation of the anastomosis by Scanning Electron Microscopy (SEM) and Magnetic Resonance Imaging (MRI) demonstrated that the installation process does not cause damage to the vessel intima and the vascular coupling system is not exposed to the vessel lumen. Mechanical testing results showed that vessels reconnected with the vascular coupling system could withstand 12.7±2.2 N tensile force and have superior leak profiles compared to hand sutured vessels. The anastomotic process was successfully demonstrated on both arteries and veins in cadaver and live pigs

Characterization, sub-cellular localization and expression profiling of the isoprenylcysteine methylesterase gene family in Arabidopsis thaliana

Background: Isoprenylcysteine methylesterases (ICME) demethylate prenylated protein in eukaryotic cell. Until now, knowledge about their molecular information, localization and expression pattern is largely unavailable in plant species. One ICME in Arabidopsis, encoded by At5g15860, has been identified recently. Over-expression of At5g15860 caused an ABA hypersensitive phenotype in transgenic Arabidopsis plants, indicating that it functions as a positive regulator of ABA signaling. Moreover, ABA induced the expression of this gene in Arabidopsis seedlings. The current study extends these findings by examining the sub-cellular localization, expression profiling, and physiological functions of ICME and two other ICME-like proteins, ICME-LIKE1 and ICME-LIKE2, which were encoded by two related genes At1g26120 and At3g02410, respectively. Results: Bioinformatics investigations showed that the ICME and other two ICME-like homologs comprise a small subfamily of carboxylesterase (EC 3.1.1.1) in Arabidopsis. Sub-cellular localization of GFP tagged ICME and its homologs showed that the ICME and ICME-like proteins are intramembrane proteins predominantly localizing in the endoplasmic reticulum (ER) and Golgi apparatus. Semi-quantitative and real-time quantitative PCR revealed that the ICME and ICME-like genes are expressed in all examined tissues, including roots, rosette leaves, cauline leaves, stems, flowers, and siliques, with differential expression levels. Within the gene family, the base transcript abundance of ICME-LIKE2 gene is very low with higher expression in reproductive organs (flowers and siliques). Time-course analysis uncovered that both ICME and ICME-like genes are up-regulated by mannitol, NaCl and ABA treatment, with ICME showing the highest level of up-regulation by these treatments. Heat stress resulted in up-regulation of the ICME gene significantly but down-regulation of the ICME-LIKE1 and ICME-LIKE2 genes. Cold and dehydration stimuli led to no significant change of both ICME and ICME-like gene expression. Mutant icme-like2-1 showed increased sensitivity to ABA but slightly decreased sensitivity to salt and osmotic stresses during seed germination. Conclusions: It is concluded that the ICME family is involved in stress and ABA signaling in Arabidopsis, probably through mediating the process of demethylating prenylated proteins. Identification of these prenylated proteins will help to better understand the significance of protein prenylation in Planta

A Probabilistic Framework for Estimating the Risk of Pedestrian-Vehicle Conflicts at Intersections

Pedestrian safety has become an important research topic among various studies due to the increased number of pedestrian-involved crashes. To evaluate pedestrian safety proactively, surrogate safety measures (SSMs) have been widely used in traffic conflict-based studies as they do not require historical crashes as inputs. However, most existing SSMs were developed based on the assumption that road users would maintain constant velocity and direction. Risk estimations based on this assumption are less unstable, more likely to be exaggerated, and unable to capture the evasive maneuvers of drivers. Considering the limitations among existing SSMs, this study proposes a probabilistic framework for estimating the risk of pedestrian-vehicle conflicts at intersections. The proposed framework loosen restrictions of constant speed by predicting trajectories using a Gaussian Process Regression and accounts for the different possible driver maneuvers with a Random Forest model. Real-world LiDAR data collected at an intersection was used to evaluate the performance of the proposed framework. The newly developed framework is able to identify all pedestrian-vehicle conflicts. Compared to the Time-to-Collision, the proposed framework provides a more stable risk estimation and captures the evasive maneuvers of vehicles. Moreover, the proposed framework does not require expensive computation resources, which makes it an ideal choice for real-time proactive pedestrian safety solutions at intersections

Compressive performance of AFRP reinforced laminated bamboo stub columns

Engineered bamboo construction can be affected by natural defects, insects, corrosion, etc., which will result in damaging the mechanical properties of structural components. However, traditional reinforcement methods such as setting steel supports and increasing the cross-sectional area of components may cost a lot and cause a negative influence on the appearance of building. Many engineering practices and research works show that applying FRP (Fiber Reinforced Polymer/Fiber) sheet is an economical and efficient method for reinforcing and retrofitting building structures. Therefore, the compressive performance of AFRP (Aramid Fiber Reinforced Polymer/Fiber) reinforced laminated bamboo lumber (LBL) stub columns was studied in this paper. Through six groups (three replicates for each group) of stub columns with six different cloth ratios, the influence of AFRP on the failure pattern and mechanical properties of bamboo columns was explored. The test results showed that AFRP could effectively restrain the lateral deformation and improve the mechanical behavior of LBL columns. With the increase in cloth ratio, the ultimate strength and elastic modulus increased linearly in general, while the Poisson’s ratio gradually decreased. The reduced modulus of reinforced columns in the elastoplastic stage increased up to 161.31% compared with normal columns. Although the ductility of LBL columns laterally wrapped by AFRP was greatly improved, the initial stiffness, yield point and turning points between elastoplastic stage and plastic stage basically remained unchanged in contrast to unreinforced columns. Based on the test results, an empirical equation considering the cloth ratio was proposed to calculate the ultimate strength of AFRP reinforced LBL columns, using ‘Lam and Teng’ model. In addition, a simplified equation was also proposed to calculate the compressive strength of reinforced LBL columns derived from Mises yield criterion. The results of this work can be a reference to promote the application of strengthening and retrofitting engineered bamboo structure with FRP

Current trends and developments in progressive collapse research on reinforced concrete flat plate structures

Progressive collapse of structures caused by extreme or accidental loads may lead to significant loss of life and property. Considerable research efforts have been made to date to mitigate the probability of progressive collapse and its consequences. This study summarises the fundamentals of progressive collapse in relation to the existing theoretical concepts and understanding. Specifically the existing theories pertinent to progressive collapse of building structures, in particular reinforced concrete (RC) flat plates, are examined from the following four key aspects: (1) definition of progressive collapse from deformation and/or strength perspectives with respect to the failure criteria of structural members and the entire structural system; (2) failure mechanisms of load-bearing systems undergoing progressive collapse with respect to the structural ultimate capacity, which has not been considered in the design process; (3) research methodologies for investigating collapse mechanisms, with emphases on experimental and numerical approaches; and (4) collapse-resistant design principles as covered in several international design standards in which a number of robustness requirements have been recognised. Based on the schematic review of the current trends and developments, gaps and limitations in progressive collapse research are identified and a new research direction is established to advance the progressive collapse study of RC flat plate structures

Lateral Sharpening of Cortical Frequency Tuning by Approximately Balanced Inhibition

SummaryCortical inhibition plays an important role in shaping neuronal processing. The underlying synaptic mechanisms remain controversial. Here, in vivo whole-cell recordings from neurons in the rat primary auditory cortex revealed that the frequency tuning curve of inhibitory input was broader than that of excitatory input. This results in relatively stronger inhibition in frequency domains flanking the preferred frequencies of the cell and a significant sharpening of the frequency tuning of membrane responses. The less selective inhibition can be attributed to a broader bandwidth and lower threshold of spike tonal receptive field of fast-spike inhibitory neurons than nearby excitatory neurons, although both types of neurons receive similar ranges of excitatory input and are organized into the same tonotopic map. Thus, the balance between excitation and inhibition is only approximate, and intracortical inhibition with high sensitivity and low selectivity can laterally sharpen the frequency tuning of neurons, ensuring their highly selective representation

Broad Inhibition Sharpens Orientation Selectivity by Expanding Input Dynamic Range in Mouse Simple Cells

SummaryOrientation selectivity (OS) is an emergent property in the primary visual cortex (V1). How OS arises from synaptic circuits remains unsolved. Here, in vivo whole-cell recordings in the mouse V1 revealed that simple cells received broadly tuned excitation and even more broadly tuned inhibition. Excitation and inhibition shared a similar orientation preference and temporally overlapped substantially. Neuron modeling and dynamic-clamp recording further revealed that excitatory inputs alone would result in membrane potential responses with significantly attenuated selectivity, due to a saturating input-output function of the membrane filtering. Inhibition ameliorated the attenuation of excitatory selectivity by expanding the input dynamic range and caused additional sharpening of output responses beyond unselectively suppressing responses at all orientations. This “blur-sharpening” effect allows selectivity conveyed by excitatory inputs to be better expressed, which may be a general mechanism underlying the generation of feature-selective responses in the face of strong excitatory inputs that are weakly biased

Dcc Mediates Functional Assembly of Peripheral Auditory Circuits.

Proper structural organization of spiral ganglion (SG) innervation is crucial for normal hearing function. However, molecular mechanisms underlying the developmental formation of this precise organization remain not well understood. Here, we report in the developing mouse cochlea that deleted in colorectal cancer (Dcc) contributes to the proper organization of spiral ganglion neurons (SGNs) within the Rosenthal\u27s canal and of SGN projections toward both the peripheral and central auditory targets. In Dcc mutant embryos, mispositioning of SGNs occurred along the peripheral auditory pathway with misrouted afferent fibers and reduced synaptic contacts with hair cells. The central auditory pathway simultaneously exhibited similar defective phenotypes as in the periphery with abnormal exit of SGNs from the Rosenthal\u27s canal towards central nuclei. Furthermore, the axons of SGNs ascending into the cochlear nucleus had disrupted bifurcation patterns. Thus, Dcc is necessary for establishing the proper spatial organization of SGNs and their fibers in both peripheral and central auditory pathways, through controlling axon targeting and cell migration. Our results suggest that Dcc plays an important role in the developmental formation of peripheral and central auditory circuits, and its mutation may contribute to sensorineural hearing loss

Sensory processing deficits and related cortical pathological changes in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily affecting cognitive functions. However, sensory deficits in AD start to draw attention due to their high prevalence and early onsets which suggest that they could potentially serve as diagnostic biomarkers and even contribute to the disease progression. This literature review examines the sensory deficits and cortical pathological changes observed in visual, auditory, olfactory, and somatosensory systems in AD patients, as well as in various AD animal models. Sensory deficits may emerge at the early stages of AD, or even precede the cognitive decline, which is accompanied by cortical pathological changes including amyloid-beta deposition, tauopathy, gliosis, and alterations in neuronal excitability, synaptic inputs, and functional plasticity. Notably, these changes are more pronounced in sensory association areas and superficial cortical layers, which may explain the relative preservation of basic sensory functions but early display of deficits of higher sensory functions. We propose that sensory impairment and the progression of AD may establish a cyclical relationship that mutually perpetuates each condition. This review highlights the significance of sensory deficits with or without cortical pathological changes in AD and emphasizes the need for further research to develop reliable early detection and intervention through sensory systems