Showing papers by "The Chinese University of Hong Kong published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Observation of Electron-Antineutrino Disappearance at Daya Bay

Abstract: The Daya Bay Reactor Neutrino Experiment has measured a nonzero value for the neutrino mixing angle θ13 with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GW_(th) reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43 000 ton–GW_(th)–day live-time exposure in 55 days, 10 416 (80 376) electron-antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is R=0.940± 0.011(stat.)±0.004(syst.). A rate-only analysis finds sin^22θ_(13)=0.092±0.016(stat.)±0.005(syst.) in a three-neutrino framework.

Architecture of the human regulatory network derived from ENCODE data

Abstract: Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.

Abstract: Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier "Asian-Pacific consensus statement on the management of chronic hepatitis B" was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.

Nonfinancial Disclosure and Analyst Forecast Accuracy: International Evidence on Corporate Social Responsibility Disclosure

Abstract: We examine the relationship between disclosure of nonfinancial information and analyst forecast accuracy using firm-level data from 31 countries. We use the issuance of stand-alone corporate social responsibility (CSR) reports to proxy for disclosure of nonfinancial information. We find that the issuance of stand-alone CSR reports is associated with lower analyst forecast error. This relationship is stronger in countries that are more stakeholder-oriented—i.e., in countries where CSR performance is more likely to affect firm financial performance. The relationship is also stronger for firms and countries with more opaque financial disclosure, suggesting that issuance of stand-alone CSR reports plays a role complementary to financial disclosure. These results hold after we control for various factors related to firm financial transparency and other potentially confounding institutional factors. Collectively, our findings have important implications for academics and practitioners in understanding...

Facile Synthesis of Nitrogen-Doped Graphene via Pyrolysis of Graphene Oxide and Urea, and its Electrocatalytic Activity toward the Oxygen-Reduction Reaction

Abstract: excellent thermal conductivity, [ 2 ] and a high optical transparency. [ 3 ] These properties lead to very promising applications of graphene in electronic devices, [ 4 ] transparent electrodes, [ 5 ] and energy-storage devices. [ 6 , 7 ] Recently, it was found that graphene has an extraordinary catalytic activity. [ 8–14 ] For example, N-doped graphene has a high catalytic activity toward the oxygen-reduction reaction (ORR). [ 8 ] Furthermore, graphene oxide (GO), an important derivative of graphene, is an effi cient catalyst for oxidation and hydration reactions of various alcohols, [ 9 ] whereas reduced GO can be used for catalyzing the hydrogenation of nitrobenzene. [ 10 ] Studies have shown that the heteroatoms in graphene derivatives, such as N and O, play a critical role in their catalytic activities. [ 10 , 15 , 16 ] Thus, the introduction of dopants into the graphene lattice has been the focus of much research in order to achieve a high catalytic activity toward target reactions. Among various doped graphenes, nitrogen-doped graphene (NG) has attracted much attention because of its high catalytic activity toward the ORR – the electrode reaction that often limits the performance of the cathode in a fuel cell or a metalair battery. Conventional Pt-based catalysts have a high intrinsic catalytic activity toward the ORR, but suffer from the drawbacks of high cost, poor long-term stability, and susceptibility to the crossover effect, which hinder the commercial viability of Ptloaded fuel cells. [ 17 ] Thus the search for an alternative catalyst, such as NG, is of great importance in replacing these expensive Pt-based catalysts. To prepare NG, chemical-vapor deposition in the presence of N-containing precursors is the most-common method; [ 18 ] arc discharge of graphite electrodes in a H 2 /pyridine or H 2 /NH 3 atmosphere can also produce NG. [ 19 ] However, the extremely low yield and high cost of these methods limit their application only to fundamental studies. Later, it was found that GO can be

Structure extraction from texture via relative total variation

Abstract: It is ubiquitous that meaningful structures are formed by or appear over textured surfaces. Extracting them under the complication of texture patterns, which could be regular, near-regular, or irregular, is very challenging, but of great practical importance. We propose new inherent variation and relative total variation measures, which capture the essential difference of these two types of visual forms, and develop an efficient optimization system to extract main structures. The new variation measures are validated on millions of sample patches. Our approach finds a number of new applications to manipulate, render, and reuse the immense number of "structure with texture" images and drawings that were traditionally difficult to be edited properly.

Patterns of treatment response in newly diagnosed epilepsy

Abstract: Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy. Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; and D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year. Results: A total of 1,098 patients were included (median age 32 years, range 9–93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens ( p Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.

An International Comparison of Capital Structure and Debt Maturity Choices

Abstract: This study examines how the institutional environment influences capital structure and debt maturity choices of firms in 39 developed and developing countries. We find that a country's legal and tax system, corruption, and the preferences of capital suppliers explain a significant portion of the variation in leverage and debt maturity ratios. Specifically, firms in more corrupt countries and those with weaker laws tend to use more debt, especially short-term debt; explicit bankruptcy codes and deposit insurance are associated with higher leverage and more long-term debt. More debt is used in countries where there is a greater tax gain from leverage. © 2012 Michael G. Foster School of Business, University of Washington, Seattle, WA 98195.

Human reidentification with transferred metric learning

Abstract: Human reidentification is to match persons observed in non-overlapping camera views with visual features for inter-camera tracking. The ambiguity increases with the number of candidates to be distinguished. Simple temporal reasoning can simplify the problem by pruning the candidate set to be matched. Existing approaches adopt a fixed metric for matching all the subjects. Our approach is motivated by the insight that different visual metrics should be optimally learned for different candidate sets. We tackle this problem under a transfer learning framework. Given a large training set, the training samples are selected and reweighted according to their visual similarities with the query sample and its candidate set. A weighted maximum margin metric is online learned and transferred from a generic metric to a candidate-set-specific metric. The whole online reweighting and learning process takes less than two seconds per candidate set. Experiments on the VIPeR dataset and our dataset show that the proposed transferred metric learning significantly outperforms directly matching visual features or using a single generic metric learned from the whole training set.

Cooperative Output Regulation of Linear Multi-Agent Systems

Abstract: In this technical note, we consider the cooperative output regulation of linear multi-agent systems. The overall system consists of two groups of subsystems. While the first group of subsystems can access the exogenous signal, the second cannot. As a result, the problem cannot be solved by the decentralized approach. By devising a distributed observer, we can solve the problem by a dynamic full information distributed control scheme. The problem can also be viewed as a generalization of some results of the leader-following consensus problem of multi-agent systems.

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

Abstract: We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)

Abstract: Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.

Fused matrix factorization with geographical and social influence in location-based social networks

Abstract: Recently, location-based social networks (LBSNs), such as Gowalla, Foursquare, Facebook, and Brightkite, etc, have attracted millions of users to share their social friendship and their locations via check-ins The available check-in information makes it possible to mine users' preference on locations and to provide favorite recommendations Personalized Point-of-interest (POI) recommendation is a significant task in LBSNs since it can help targeted users explore their surroundings as well as help third-party developers to provide personalized services To solve this task, matrix factorization is a promising tool due to its success in recommender systems However, previously proposed matrix factorization (MF) methods do not explore geographical influence, eg, multi-center check-in property, which yields suboptimal solutions for the recommendation In this paper, to the best of our knowledge, we are the first to fuse MF with geographical and social influence for POI recommendation in LBSNs We first capture the geographical influence via modeling the probability of a user's check-in on a location as a Multicenter Gaussian Model (MGM) Next, we include social information and fuse the geographical influence into a generalized matrix factorization framework Our solution to POI recommendation is efficient and scales linearly with the number of observations Finally, we conduct thorough experiments on a large-scale real-world LBSNs dataset and demonstrate that the fused matrix factorization framework with MGM utilizes the distance information sufficiently and outperforms other state-of-the-art methods significantly

Bayesian face revisited: a joint formulation

Abstract: In this paper, we revisit the classical Bayesian face recognition method by Baback Moghaddam et al. and propose a new joint formulation. The classical Bayesian method models the appearance difference between two faces. We observe that this "difference" formulation may reduce the separability between classes. Instead, we model two faces jointly with an appropriate prior on the face representation. Our joint formulation leads to an EM-like model learning at the training time and an efficient, closed-formed computation at the test time. On extensive experimental evaluations, our method is superior to the classical Bayesian face and many other supervised approaches. Our method achieved 92.4% test accuracy on the challenging Labeled Face in Wild (LFW) dataset. Comparing with current best commercial system, we reduced the error rate by 10%.

WO3 nanorods/graphene nanocomposites for high-efficiency visible-light-driven photocatalysis and NO2 gas sensing

Abstract: One-dimensional (1-D) nanostructures are of great importance due to their superior charge transport properties. Anchoring 1-D semiconductor nanomaterials on graphene offers potential advantages in photoelectrochemical and sensing applications. This paper presents a systematic investigation on the incorporation of WO3 nanorods and graphene for high-efficiency visible-light-driven photocatalysis and NO2 gas sensing. This novel composite shows remarkably enhanced performance compared to pure WO3 nanorods for these applications. The high photocatalytic activity of the WO3/graphene nanocomposite is found to be related to the increased adsorption toward chemical species, enhanced light absorption and efficient charge separation and transfer. Meanwhile, the improved conductivity, specific electron transfer and increased gas adsorption also contribute to their superior sensitivity and selectivity to NO2 gas.

Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography

Abstract: Objective Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population. Methods Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. Results Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was Conclusion NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.

Global well-posedness of classical solutions with large oscillations and vacuum to the three-dimensional isentropic compressible Navier-Stokes equations

Abstract: We establish the global existence and uniqueness of classical solutions to the Cauchy problem for the isentropic compressible Navier-Stokes equations in three spatial dimensions with smooth initial data that are of small energy but possibly large oscillations with constant state as far field, which could be either vacuum or nonvacuum. The initial density is allowed to vanish, and the spatial measure of the set of vacuum can be arbitrarily large; in particular, the initial density can even have compact support. These results generalize previous results on classical solutions for initial densities being strictly away from vacuum and are the first for global classical solutions that may have large oscillations and can contain vacuum states. © 2012 Wiley Periodicals, Inc.

Plasmon-Controlled Fluorescence: Beyond the Intensity Enhancement

Abstract: Control over light absorption and emission using plasmonic nanostructures is an enabling technology, which can dramatically enhance the performances of existing optical and optoelectronic devices, such as solar cells, light-emitting devices, biosensors, and high-resolution fluorescence microscopes. This Perspective takes fluorescence as an example, illustrating how plasmonic nanostructures can control the light absorption and emission of nanoscale optical species. The origins of fluorescence intensity enhancements will be first discussed. Different parameters that can largely affect the interactions between plasmonic nanostructures and fluorophore molecules will be examined, including the distance between the fluorophore molecule and the metal nanostructure and the wavelengths of their respective optical responses. The role of plasmonic nanostructures on fluorescence will then be reconsidered from the perspective of optical nanoantennas. We expect that more functionalities of plasmonic nanostructures as o...

VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis

Abstract: A proline to serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB) causes some dominantly inherited familial forms of motor neuron disease including amyotrophic lateral sclerosis (ALS) type-8 VAPB is an integral endoplasmic reticulum (ER) protein whose amino-terminus projects into the cytosol Overexpression of ALS mutant VAPBP56S disrupts ER structure but the mechanisms by which it induces disease are not properly understood Here we show that VAPB interacts with the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51) ER and mitochondria are both stores for intracellular calcium (Ca2+) and Ca2+ exchange between these organelles occurs at regions of ER that are closely apposed to mitochondria These are termed mitochondria-associated membranes (MAM) We demonstrate that VAPB is a MAM protein and that loss of either VAPB or PTPIP51 perturbs uptake of Ca2+ by mitochondria following release from ER stores Finally, we demonstrate that VAPBP56S has altered binding to PTPIP51 and increases Ca2+ uptake by mitochondria following release from ER stores Damage to ER, mitochondria and Ca2+ homeostasis are all seen in ALS and we discuss the implications of our findings in this context

Cooperative Output Regulation With Application to Multi-Agent Consensus Under Switching Network

Abstract: In this paper, we consider the cooperative output regulation of linear multi-agent systems under switching network. The problem can be viewed as a generalization of the leader-following consensus problem of multi-agent systems. Due to the limited information exchanges of different subsystems, the problem cannot be solved by the decentralized approach and is not allowed to be solved by the centralized control. By devising a distributed observer network, we can solve the problem by both dynamic state feedback control and dynamic measurement output feedback control. As an application of our main result, we show that a special case of our results leads to the solution of the leader-following consensus problem of linear multi-agent systems.

Vehicle-to-Aggregator Interaction Game

Abstract: Electric vehicles (EVs) are likely to become very popular worldwide within the next few years. With possibly millions of such vehicles operating across the country, one can establish a distributed electricity storage system that comprises of the EVs' batteries with a huge total storage capacity. This can help the power grid by providing various ancillary services, once an effective vehicle-to-grid (V2G) market is established. In this paper, we propose a new game-theoretic model to understand the interactions among EVs and aggregators in a V2G market, where EVs participate in providing frequency regulation service to the grid. We develop a smart pricing policy and design a mechanism to achieve optimal frequency regulation performance in a distributed fashion. Simulation results show that our proposed pricing model and designed mechanism work well and can benefit both EVs (in terms of obtaining additional income) and the grid (in terms of achieving the frequency regulation command signal).