Victor C. S. Lee

Effective Treatment of Metastatic Forms of Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma with a Novel Adenovirus-Based Adoptive Immunotherapy

Nasopharyngeal carcinoma (NPC) is endemic in China and Southeast Asia where it is tightly associated with infections by Epstein-Barr virus (EBV). The role of tumor-associated viral antigens in NPC renders it an appealing candidate for cellular immunotherapy. In earlier preclinical studies, a novel adenoviral vector-based vaccine termed AdE1-LMPpoly has been generated that encodes EBV nuclear antigen-1 (EBNA1) fused to multiple CD8(+) T-cell epitopes from the EBV latent membrane proteins, LMP1 and LMP2. Here, we report the findings of a formal clinical assessment of AdE1-LMPpoly as an immunotherapeutic tool for EBV-associated recurrent and metastatic NPC. From a total of 24 patients with NPC, EBV-specific T cells were successfully expanded from 16 patients with NPC (72.7%), whereas six patients with NPC (27.3%) showed minimal or no expansion of virus-specific T cells. Transient increase in the frequencies of LMP1&2- and EBNA1-specific T-cell responses was observed after adoptive transfer to be associated with grade I flu-like symptoms and malaise. The time to progression in these patients ranged from 38 to 420 days with a mean time to progression of 136 days. Compared with patients who did not receive T cells, the median overall survival increased from 220 to 523 days. Taken together, our findings show that adoptive immunotherapy with AdE1-LMPpoly vaccine is safe and well tolerated and may offer clinical benefit to patients with NPC.

On transaction processing with partial validation and timestamp ordering in mobile broadcast environments

Conventional concurrency control protocols are inapplicable in mobile broadcast environments due to a number of constraints of wireless communications. Previous studies are focused on efficient processing of read-only transactions at the mobile clients, neglecting update transactions. In this paper, we design a new protocol for processing both read-only and update mobile transactions. The protocol can detect data conflicts at an early stage at the mobile clients and resolve data conflicts flexibly using dynamic adjustment of timestamp ordering. Early data conflict detection saves processing and communication resources, while dynamic adjustment of timestamp ordering allows more schedules of transaction executions such that unnecessary transaction aborts can be avoided. We performed extensive simulation studies to evaluate the effectiveness of these two features for the performance of the new protocol. The analysis of simulation results showed that both features are effective and contribute differently to the satisfactory performance of the protocol.

Cooperative data scheduling in hybrid vehicular ad hoc networks: VANET as a software defined network

This paper presents the first study on scheduling for cooperative data dissemination in a hybrid infrastructure-to-vehicle (I2V) and vehicle-to-vehicle (V2V) communication environment. We formulate the novel problem of cooperative data scheduling (CDS). Each vehicle informs the road-side unit (RSU) the list of its current neighboring vehicles and the identifiers of the retrieved and newly requested data. The RSU then selects sender and receiver vehicles and corresponding data for V2V communication, while it simultaneously broadcasts a data item to vehicles that are instructed to tune into the I2V channel. The goal is to maximize the number of vehicles that retrieve their requested data. We prove that CDS is NP-hard by constructing a polynomial-time reduction from the Maximum Weighted Independent Set (MWIS) problem. Scheduling decisions are made by transforming CDS to MWIS and using a greedy method to approximately solve MWIS. We build a simulation model based on realistic traffic and communication characteristics and demonstrate the superiority and scalability of the proposed solution. The proposed model and solution, which are based on the centralized scheduler at the RSU, represent the first known vehicular ad hoc network (VANET) implementation of software defined network (SDN) concept.

PRODUCT-SUBSTRATE ENGINEERING BY BACTERIA : STUDIES ON CLAVAMINATE SYNTHASE, A TRIFUNCTIONAL DIOXYGENASE

Evidence is presented that clavaminate synthase (CS) catalyses three oxidative reactions in the clavulanic acid biosynthetic pathway. The first CS catalysed step (hydroxylation) is separated from the latter two (oxidative cyclisation and desaturation) by the action of a hydrolytic enzyme, proclavaminate amidinohydrolase, which modifies (or ‘mutates’) the sidechain of the product of the first reaction thereby converting it into a substrate for the second CS catalysed reaction.

Coding-Based Data Broadcast Scheduling in On-Demand Broadcast

According to data broadcast, we can satisfy multiple requests for the same data item in a broadcast tick. However, there is no significant breakthrough in performance improvement until recently that some studies proposed to use network coding in data broadcast. After broadcasting an encoded packet which encodes a number of data items, multiple clients can retrieve different requested data items in a broadcast tick. This not only utilizes bandwidth more efficiently, but also improves system performance. In this work, we propose a generalized encoding framework to incorporate network coding into data scheduling algorithms for on-demand broadcast. In the framework, data scheduling can be formulated as a weighted maximum clique problem in a graph where the weight of the clique is defined according to the performance objectives of the applications. Under the proposed framework, existing data scheduling algorithms for on-demand broadcast can be migrated into their corresponding coding versions while preserving their original criteria in scheduling data items. Our simulation results using a number of representative scheduling algorithms show that significant performance improvement can be achieved with coding.

Improving Positioning Accuracy Using GPS Pseudorange Measurements for Cooperative Vehicular Localization

Accurate positioning is a key factor for enabling innovative applications in intelligent transportation systems. Cutting-edge communication technologies make cooperative localization a promising approach for accurate vehicle positioning. In this paper, we first propose a ranging technique called weighted least squares double difference (WLS-DD), which is used to detect intervehicle distances based on the sharing of GPS pseudorange measurements and a weighted least squares method. It takes the carrier-to-noise ratio (CNR) of raw pseudorange measurements into consideration for mitigating noises so that it can improve the accuracy of the distance detection. We show the superiority of WLS-DD by conducting a series of field experiments. Based on intervehicle distance detection, we propose a distributed location estimate algorithm (DLEA) to improve the accuracy of vehicle positioning. The implementation of DLEA only relies on inaccurate GPS pseudorange measurements and the obtained intervehicle distances without using any reference points for positioning correction. Moreover, to evaluate the joint effect of WLS-DD and DLEA, we derive a data fitting model based on the observed distance detection bias from field experiments, which generates parameters in a variety of environments for performance evaluation. Finally, we demonstrate the effectiveness of the proposed solutions via a comprehensive simulation study.

Scheduling real-time requests in on-demand data broadcast environments

On-demand broadcast is an attractive data dissemination method for mobile and wireless computing. In this paper, we propose a new online preemptive scheduling algorithm, called PRDS that incorporates urgency, data size and number of pending requests for real-time on-demand broadcast system. Furthermore, we use pyramid preemption to optimize performance and reduce overhead. A series of simulation experiments have been performed to evaluate the real-time performance of our algorithm as compared with other previously proposed methods. The experimental results show that our algorithm substantially outperforms other algorithms over a wide range of workloads and parameter settings.

Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis.

BackgroundwLocal failure is an important cause of morbidity and mortality in nasopharyngeal carcinoma (NPC). Although surgery or brachytherapy may be feasible in selected cases, most patients with local failure require external beam re-irradiation. Stereotactic radiation using single or multiple fractions have been employed in re-irradiation of NPC, but the optimal fractionation scheme and dose are not clear.MethodsRecords of 125 NPC patients who received salvage stereotactic radiation were reviewed. A matched-pair design was used to select patients with similar prognostic factors who received stereotactic re-irradiation using single fraction (SRS) or multiple fractions (SRM). Eighty-six patients were selected with equal number in SRS and SRM groups. All patients were individually matched for failure type (persistent or recurrent), rT stage (rT1-2 or rT3-4), and tumor volume (≤ 5 cc, >5–10 cc, or >10 cc). Median dose was 12.5 Gy in single fraction by SRS, and 34 Gy in 2–6 fractions by SRM.ResultsLocal control rate was better in SRM group although overall survival rates were similar. One- and 3-year local failure-free rates were 70% and 51% in SRS group compared with 91% and 83% in SRM group (p = 0.003). One- and 3-year overall survival rates were 98% and 66% in SRS group compared with 78% and 61% in SRM group (p = 0.31). The differences in local control were mainly observed in recurrent or rT2-4 disease. Incidence of severe late complications was 33% in SRS group vs. 21% in SRM group, including brain necrosis (16% vs. 12%) and hemorrhage (5% vs. 2%).ConclusionOur study showed that SRM was superior to SRS in salvaging local failures of NPC, especially in the treatment of recurrent and rT2-4 disease. In patient with local failure of NPC suitable for stereotactic re-iradiation, use of fractionated treatment is preferred.

On-demand broadcast for multiple-item requests in a multiple-channel environment

On-demand broadcast is an effective approach to disseminating data in mobile computing environments. Substantial efforts have been devoted to improving the scheduling efficiency of on-demand broadcast. Previous studies focused mainly on the case of scheduling single-item requests in single-channel environments. However, requesting multiple dependent data items is common in many advanced applications such as electronic stock trading and traffic information enquiry services. In addition, multi-channel architectures are widely deployed in data broadcast systems. In this work, we investigate the issues arising in scheduling multi-item requests in multi-channel on-demand broadcast environments. Two problems, namely, the request starvation problem and the bandwidth utilization problem are identified in existing algorithms. To tackle the observed problems, an innovative algorithm is proposed. Results from our simulation study demonstrate the superiority of the proposed algorithm.

Efficient validation of mobile transactions in wireless environments

In broadcast environments, the limited bandwidth of the upstream communication channel from the mobile clients to the server bars the application of conventional concurrency control protocols. In this paper, we propose a new variant of the optimistic concurrency control (OCC) protocol that is suitable for broadcast environments. At the server, forward validation of a transaction is done against currently running transactions, including mobile transactions and server transactions. At the mobile clients, partial backward validation of a transaction is done against committed transactions at the beginning of every broadcast cycle. Upon completion of execution, read-only mobile transactions can be validated and committed locally and update mobile transactions are sent to the server for final validation. These update transactions have a better chance of commitment because they have gone through the partial backward validation. In addition to the nice properties of conventional OCC protocols, this protocol provides autonomy between the mobile clients and the server with minimum upstream communication, which is a desirable feature to the scalability of applications running in broadcast environments. This protocol is able to process both update transactions and read-only transactions at the mobile clients at low space and processing overheads.