The Phonological System of A Xin\u27an Idiolect

My idiolect, a Xin’an idiolect, belongs to the Wuxi dialect, which is the northern Wu dialect. It carries most of the characteristics of the Wuxi dialect, such as the tripartite division of the manner of articulation of initial stop consonants. However, with the special geographic position, on the bounty of Wuxi dialect from the northwest area to southeast area and connected with Suzhou city, my idiolect shows its unique features, such as the condition of the retroflex. This study analyzes the phonological system of the idiolect and discusses the features. Since the dialect of the suburban area of the Wuxi is rare, it was only documented in the local chronicles; therefore the study is a good supplemental material to the Wuxi dialect. Moreover, using the idiolect is like to use the phonological material with the specific area and social identity. It is well known that the variation of the language is related to the area, to the speaker’s social identity and to the situation, therefore the specific idiolect definitely will benefit researchers to analyze the dialect. Furthermore, idiolect is also a good sample to study the language diversity among the different social classes, which need to get more attention from scholars. With the influence of the Mandarin and the surrounding dialects, some phonological features of my idiolect are in the variation, such as the sharp and rounded sounds. In the thesis, the theory of the language contact is applied to explain my idiolect

Parameter-uniform numerical methods for problems with layer phenomena: Application in mathematical finance

Ph.DDOCTOR OF PHILOSOPH

Image edge detection with a photonic spiking VCSEL-neuron

We report both experimentally and in theory on the detection of edge features in digital images with an artificial optical spiking neuron based on a vertical-cavity surface-emitting laser (VCSEL). The latter delivers fast (< 100 ps) neuron-like optical spikes in response to optical inputs pre-processed using convolution techniques; hence representing image feature information with a spiking data output directly in the optical domain. The proposed technique is able to detect target edges of different directionalities in digital images by applying individual kernel operators and can achieve complete image edge detection using gradient magnitude. Importantly, the neuromorphic (brain-like) spiking edge detection of this work uses commercially sourced VCSELs exhibiting responses at sub-nanosecond rates (many orders of magnitude faster than biological neurons) and operating at the important telecom wavelength of 1300 nm; hence making our approach compatible with optical communication and data-centre technologies

Inhibition of OATP1B1 by tyrosine kinase inhibitors: In vitro-in vivo correlations

Background:Several tyrosine kinase inhibitors (TKIs) can decrease docetaxel clearance in patients by an unknown mechanism. We hypothesised that these interactions are mediated by the hepatic uptake transporter OATP1B1.Methods:The influence of 16 approved TKIs on transport was studied in vitro using HEK293 cells expressing OATP1B1 or its mouse equivalent Oatp1b2. Pharmacokinetic studies were performed with Oatp1b2-knockout and OATP1B1-transgenic mice.Results:All docetaxel-interacting TKIs, including sorafenib, were identified as potent inhibitors of OATP1B1 in vitro. Although Oatp1b2 deficiency in vivo was associated with increased docetaxel exposure, single- or multiple-dose sorafenib did not influence docetaxel pharmacokinetics.Conclusion: These findings highlight the importance of identifying proper preclinical models for verifying and predicting TKI-chemotherapy interactions involving transporters

All-optical neuromorphic binary convolution with a spiking VCSEL neuron for image gradient magnitudes

All-optical binary convolution with a photonic spiking vertical-cavity surface-emitting laser (VCSEL) neuron is proposed and demonstrated experimentally for the first time, to the best of our knowledge. Optical inputs, extracted from digital images and temporally encoded using rectangular pulses, are injected in the VCSEL neuron, which delivers the convolution result in the number of fast (<100 ps long) spikes fired. Experimental and numerical results show that binary convolution is achieved successfully with a single spiking VCSEL neuron and that all-optical binary convolution can be used to calculate image gradient magnitudes to detect edge features and separate vertical and horizontal components in source images. We also show that this all-optical spiking binary convolution system is robust to noise and can operate with high-resolution images. Additionally, the proposed system offers important advantages such as ultrafast speed, high-energy efficiency, and simple hardware implementation, highlighting the potentials of spiking photonic VCSEL neurons for high-speed neuromorphic image processing systems and future photonic spiking convolutional neural networks

Neuromorphic object edge detection with artificial photonic spiking VCSEL-neurons

Fast spiking Vertical Cavity Surface Emitting Laser neurons are used to reveal neuromorphic object edge information in digital images. Input integration and thresholding are used in tandem with convolution to create a photonic spiking node with high prospects for convolutional neural networks and computer vision

A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities

In recent years, various endogenous compounds have been proposed as putative biomarkers for the hepatic uptake transporters OATP1B1 and OATP1B3 that have the potential to predict transporter-mediated drug-drug interactions (DDIs). However, these compounds have often been identified from top-down strategies and have not been fully utilized as a substitute for traditional DDI studies. In an attempt to eliminate observer bias in biomarker selection, we applied a bottom-up, untargeted metabolomics screening approach in mice and found that plasma levels of the conjugated bile acid chenodeoxycholate-24-glucuronide (CDCA-24G) are particularly sensitive to deletion of the orthologous murine transporter Oatp1b2 (31-fold increase vs. wild type) or the entire Oatp1a/1b(-/-)cluster (83-fold increased), whereas the humanized transgenic overexpression of hepatic OATP1B1 or OATP1B3 resulted in the partial restoration of transport function. Validation studies with the OATP1B1/OATP1B3 inhibitors rifampin and paclitaxel in vitro as well as in mice and human subjects confirmed that CDCA-24G is a sensitive and rapid response biomarker to dose-dependent transporter inhibition. Collectively, our study confirmed the ability of CDCA-24G to serve as a sensitive and selective endogenous biomarker of OATP1B-type transport function and suggests a template for the future development of biomarkers for other clinically important xenobiotic transporters.</p

Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide

The oral multikinase inhibitor sorafenib undergoes extensive UGT1A9-mediated formation of sorafenib-β-D-glucuronide (SG). Using transporter-deficient mouse models, it was previously established that SG can be extruded into bile by ABCC2 or follow a liver-to-blood shuttling loop via ABCC3-mediated efflux into the systemic circulation, and subsequent uptake in neighboring hepatocytes by OATP1B-type transporters. Here we evaluated the possibility that this unusual process, called hepatocyte hopping, is also operational in humans and can be modulated through pharmacological inhibition. We found that SG transport by OATP1B1 or murine Oatp1b2 was effectively inhibited by rifampin, and that this agent can significantly increase plasma levels of SG in wildtype mice, but not in Oatp1b2-deficient animals. In human subjects receiving sorafenib, rifampin acutely increased the systemic exposure to SG. Our study emphasizes the need to consider hepatic handling of xenobiotic glucuronides in the design of drug-drug interaction studies of agents that undergo extensive phase II conjugation

Hardware-algorithm collaborative computing with photonic spiking neuron chip based on integrated Fabry-P\'erot laser with saturable absorber

Photonic neuromorphic computing has emerged as a promising avenue toward building a low-latency and energy-efficient non-von-Neuman computing system. Photonic spiking neural network (PSNN) exploits brain-like spatiotemporal processing to realize high-performance neuromorphic computing. However, the nonlinear computation of PSNN remains a significant challenging. Here, we proposed and fabricated a photonic spiking neuron chip based on an integrated Fabry-P\'erot laser with a saturable absorber (FP-SA) for the first time. The nonlinear neuron-like dynamics including temporal integration, threshold and spike generation, refractory period, and cascadability were experimentally demonstrated, which offers an indispensable fundamental building block to construct the PSNN hardware. Furthermore, we proposed time-multiplexed spike encoding to realize functional PSNN far beyond the hardware integration scale limit. PSNNs with single/cascaded photonic spiking neurons were experimentally demonstrated to realize hardware-algorithm collaborative computing, showing capability in performing classification tasks with supervised learning algorithm, which paves the way for multi-layer PSNN for solving complex tasks.Comment: 10 pages, 8 figure