Derek Zhang - Academia.edu (original) (raw)

Papers by Derek Zhang

arXiv (Cornell University), Dec 14, 2018

We propose a secure computation solution for blockchain networks. The correctness of computation ... more We propose a secure computation solution for blockchain networks. The correctness of computation is verifiable even under malicious majority condition using information-theoretic Message Authentication Code (MAC), and the privacy is preserved using Secret-Sharing. With state-ofthe-art multiparty computation protocol and a layer2 solution, our privacy-preserving computation guarantees data security on blockchain, cryptographically, while reducing the heavy-lifting computation job to a few nodes. This breakthrough has several implications on the future of decentralized networks. First, secure computation can be used to support Private Smart Contracts, where consensus is reached without exposing the information in the public contract. Second, it enables data to be shared and used in trustless network, without disclosing the raw data during data-at-use, where data ownership and data usage is safely separated. Last but not least, computation and verification processes are separated, which can be perceived as computational sharding, this effectively makes the transaction processing speed linear to the number of participating nodes. Our objective is to deploy our secure computation network as an layer2 solution to any blockchain system. Smart Contracts[41] will be used as bridge to link the blockchain and computation networks. Additionally, they will be used as verifier to ensure that outsourced computation is completed correctly. In order to achieve this, we first develop a general MPC network with advanced features, such as: 1) Secure Computation, 2) Off-chain Computation, 3) Verifiable Computation, and 4)Support dApps' needs like privacy-preserving data exchange. The remainder of this paper is organized as follows: Section 1 introduces the real world motivations which inspired us to build a secure computation network. Following motivations, we highlight our contributions in section 2. We then cover the background of secure computation, along with a comparison of similar technologies. Our system overview is presented in section 4. There, we briefly describe our system design and implementation. In section 5-7, we discuss, in detail, the major components of our multiparty computation protocol, secure computation process, and considerations in cryptoeconomics. Lastly, we review the implications and applications of the real world; this includes ecosystem design, business cases, and milestones.

BioTech

The American cranberry, Vaccinium macrocarpon, contains fibers and (poly)phenols that could exert... more The American cranberry, Vaccinium macrocarpon, contains fibers and (poly)phenols that could exert health-promoting effects through modulation of gut microbiota. This study aimed to investigate how a freeze-dried whole cranberry powder (FCP) modulated metabolite production and microbial composition using both a 48-h incubation strategy and a long-term human gut simulator study with the M-SHIME (Mucosal Simulator of the Human Intestinal Microbial Ecosystem). FCP was repeatedly administered over three weeks. The studies included five and three study subjects, respectively. In both models, FCP significantly increased levels of health-related short-chain fatty acids (SCFA: acetate, propionate and butyrate), while decreased levels of branched-chain fatty acids (markers of proteolytic fermentation). Interestingly, FCP consistently increased luminal Bacteroidetes abundances in the proximal colon of the M-SHIME (+17.5 ± 9.3%) at the expense of Proteobacteria (−10.2 ± 1.5%). At family level, ...

We are proud to announce the beta release of HanLP 2.1, which now offers 10 joint tasks on 104 la... more We are proud to announce the beta release of HanLP 2.1, which now offers 10 joint tasks on 104 languages: tokenization, lemmatization, part-of-speech tagging, token feature extraction, dependency parsing, constituency parsing, semantic role labeling, semantic dependency parsing, abstract meaning representation (AMR) parsing.

British Journal of Nutrition, 2020

Cranberries are high in polyphenols, and epidemiological studies have shown that a high-polypheno... more Cranberries are high in polyphenols, and epidemiological studies have shown that a high-polyphenol diet may reduce risk factors for diabetes and CVD. The present study aimed to determine if short-term cranberry beverage consumption would improve insulin sensitivity and other cardiovascular risk factors. Thirty-five individuals with obesity and with elevated fasting glucose or impaired glucose tolerance participated in a randomised, double-blind, placebo-controlled, parallel-designed pilot trial. Participants consumed 450 ml of low-energy cranberry beverage or placebo daily for 8 weeks. Changes in insulin sensitivity and cardiovascular risk factors including vascular reactivity, blood pressure, RMR, glucose tolerance, lipid profiles and oxidative stress biomarkers were evaluated. Change in insulin sensitivity via hyperinsulinaemic–euglycaemic clamp was not different between the two groups. Levels of 8-isoprostane (biomarker of lipid peroxidation) decreased in the cranberry group but ...

Viruses, 2021

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutat... more The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus–host interactions in order to quickly evaluate the infectious ability of mutant viruses and to develop or validate virus-inhibiting drugs. Here, we developed an ultrasensitive bioluminescent biosensor to evaluate virus–cell interactions by quantifying the interaction between the SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid, and HTP biosensor tool will significantly expedite the detection of viral mutants and the anti-COVID-19 drug discovery pro...

Did you know your muscles can feel exhausted without actually being exhausted? It turns out that ... more Did you know your muscles can feel exhausted without actually being exhausted? It turns out that your brain is just as important as your muscles when it comes to fatigue, or physical tiredness. You can experience “peripheral” fatigue, which is fatigue originating from the muscles, or you can experience central fatigue, which originates from the brain and central nervous system. By studying both the brain and the muscles, scientists can examine which is causing your fatigue. But how? Do we need to perform brain surgery to get answers? Luckily, special techniques involving stimulation of the nerves and muscles can be used instead! In this article, we illustrate how scientists determine if the tiredness you feel after exercising is caused by central or peripheral fatigue or maybe both. We will also explore the differences between the two.

Data in Brief, 2021

These data include secondary analysis of publicly available RNA-seq data from castration-resistan... more These data include secondary analysis of publicly available RNA-seq data from castration-resistant prostate cancer (CRPC) patients as well as RT-qPCR and Western blotting analyses of patient-derived xenograft models and a CRPC cell line. We applied Spearman correlation analysis to assess the relationship between canonical androgen receptor (AR) splicing and alternative AR splicing. We also assessed the ratio of AR splice variants (AR-Vs) to the full-length AR (AR-FL) at the RNA and protein levels by absolute RT-qPCR and Western blotting, respectively. These data are critical for studying the mechanisms underlying upregulated expression of AR-Vs after AR-directed therapies and the importance of AR-Vs to castration-resistant progression of prostate cancer. Data presented here are related to the research article by Ma et al., "Increased transcription and high translation efficiency lead

Cancers, 2020

The Hippo pathway is an emerging tumor suppressor signaling pathway involved in a wide range of c... more The Hippo pathway is an emerging tumor suppressor signaling pathway involved in a wide range of cellular processes. Dysregulation of different components of the Hippo signaling pathway is associated with a number of diseases including cancer. Therefore, identification of the Hippo pathway regulators and the underlying mechanism of its regulation may be useful to uncover new therapeutics for cancer therapy. The Hippo signaling pathway includes a set of kinases that phosphorylate different proteins in order to phosphorylate and inactivate its main downstream effectors, YAP and TAZ. Thus, modulating phosphorylation and dephosphorylation of the Hippo components by kinases and phosphatases play critical roles in the regulation of the signaling pathway. While information regarding kinase regulation of the Hippo pathway is abundant, the role of phosphatases in regulating this pathway is just beginning to be understood. In this review, we summarize the most recent reports on the interaction...

Pathogens, 2021

While many beneficial host–microbiota interactions have been described, imbalanced microbiota in ... more While many beneficial host–microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn’s disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type M (CTM) on adherent-invasive Escherichia coli (AIEC) LF82, a pathobiont associated with CD. Different stages of pathogenic infection were investigated: (i) colonization of the mucus layer, and (ii) adhesion to and (iii) invasion of the epithelial cells. Following 48 h of fecal batch incubation, 0.5 and 1 mM of CTM significantly altered AIEC LF82 levels in a simulated mucus layer, resulting in a decrease of 50.5% in the untreated blank, down to 43.0% and 11.4%, respectively. At 1 mM of CTM, the significant decrease in the levels of AIEC LF82 coincided with a stimulation of the metabolic activity of the background microbiota. The increased levels of health-associated acetate (+7.9 mM) an...

Cancer Letters, 2021

Upregulation of androgen receptor splice variants (AR-Vs), especially AR-V7, is associated with c... more Upregulation of androgen receptor splice variants (AR-Vs), especially AR-V7, is associated with castration resistance of prostate cancer. At the RNA level, AR-V7 upregulation is generally coupled with increased full-length AR (AR-FL); consequently, AR-V7 and AR-Vs collectively constitute a minority of the AR population. However, Western blotting showed that the relative abundance of AR-V proteins is much higher in many castration-resistant prostate cancers (CRPCs). To address the mechanism underlying this discrepancy, we analyzed RNA-seq data from ∼350 CRPC samples and found a positive correlation between all canonical and alternative AR splicing. This indicates that increased alternative splicing is not at the expense of canonical splicing. Instead, androgen deprivation releases AR-FL from repressing the transcription of the AR gene to induce coordinated increase of AR-FL and AR-V mRNAs. At the protein level, however, androgen deprivation induces AR-FL, but not AR-V, degradation. Moreover, AR-V7 is translated much faster than AR-FL. Thus, androgen-deprivation-induced AR-gene transcription and AR-FL protein decay, together with efficient AR-V7 translation, explain the discrepancy between the relative AR-V mRNA and protein abundances in many CRPCs, highlighting the inevitability of AR-V induction after endocrine therapy.

ABSTRACTThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading a... more ABSTRACTThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus-host interaction in order to quickly evaluate infectious ability of mutant virus and develop or validate virus-inhibiting drugs. Here we have developed an ultrasensitive bioluminescent biosensor to evaluate virus-cell interaction by quantifying the interaction between SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants, and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid and HTP biosensor tool will significantly expedite detection of viral mutants and anti-COVID-19 drug discovery processes.

Basic Principles, Advanced Concepts, and Applications, 2011

26.3. 2 Highlights concerning transporter-based drug interactions 420 26.3. 3 Points to consider ... more 26.3. 2 Highlights concerning transporter-based drug interactions 420 26.3. 3 Points to consider for in vivo drug interaction study design 423 26.3. 4 Issues to consider in the interpretation of drug interaction study results 424 26.4 A recent labeling example to ...

Nature Methods, 2013

This document is associated with the Bioconductor package HD2013SGI, which contains the data and ... more This document is associated with the Bioconductor package HD2013SGI, which contains the data and the R code for the statistical analysis presented in the paper Mapping genetic interactions in human cancer cells with RNAi and multiparametric phenotyping

Int. Journal of Clinical Pharmacology and Therapeutics, 2012

The purpose of this study was to conduct a pilot study in order to obtain reliable results for fu... more The purpose of this study was to conduct a pilot study in order to obtain reliable results for further planning of a well-designed pivotal trial comparing the bioequivalence (BE) of two paroxetine tablet formulations in healthy Chinese subjects. Before conducting the pivotal trial, the pilot trial enrolled 14 subjects to help in study design, establishing the recruitment period, determining pharmacokinetics (PK) time points and sample size, and assessing BE of the two formulations. The single-center, randomized, open-label, single-dose, two period crossover study with a 7-day washout interval was conducted after obtaining information from the fasted pilot trial in 72 healthy volunteers for a pivotal study under fed and fasted conditions, respectively. There were 19 PK sample collection time points employed in both the pilot and pivotal trials. A sensitive and specific liquid chromatography- tandem mass spectrometry (LC-MS/ MS) method was developed and validated for determining paroxetine in human plasma. BE between two articles was determined by calculating 90% confidence intervals (CIs) for the ratio of Cmax 91.38 - 110.39% for the pilot trial, 99.81 - 114.08% for pivotal trial under fasted condition, and 94.06 - 110.41% for pivotal trial under fed condition, AUC(0-t) 96.06 - 110.52% for pilot study, 100.88 - 113.05% for the pivotal trial under fasted condition, and 97.08 - 106.06% for pivotal study under fed condition, and AUC(0-∞) 96.17 - 110.42% for the pilot study, 100.85 - 112.81% for the pivotal trial under fasted condition and 97.22 - 106.14% for the pivotal study under fed condition, respectively. These values for the test and reference products are within the 80 - 125% interval proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a PK study in healthy Chinese volunteers, and results showed from both the pilot and pivotal studies that the two paroxetine formulations are bioequivalent in their rates and extent of absorption.

Clinical Pharmacokinetics, 2007

The chemokine receptor CCR1 is believed to play a role in several inflammatory diseases, primaril... more The chemokine receptor CCR1 is believed to play a role in several inflammatory diseases, primarily by promoting the migration of leukocytes through the endothelial barrier. Thus, a possible strategy for treating inflammatory diseases is inhibition of leukocyte infiltration by antagonising CCR1. Recently, CP-481,715 has been described as a potent and specific antagonist of CCR1. The aims of this study were to assess the safety, pharmacokinetics and pharmacodynamics of CP-481,715 along with drug interactions with ciclosporin. This was a phase I randomised, double-blind, placebo-controlled study with CP-481,715 in 78 healthy male volunteers. Subjects were administered escalating CP-481,715 doses of up to 3000 mg with food and after fasting in the single-dose study. In the drug interaction study, which was a single-dose, two-way crossover study, 12 subjects received a 300 mg dose of CP-481,715 as a suspension of polymorph A under fasted conditions, both with and without prior administration of ciclosporin. All doses of CP-481,715 were well tolerated, with linear pharmacokinetics up to the 300 mg dose. The pharmacodynamic activity of CP-481,715 was detected ex vivo by demonstrating a dose-related and linear increase in the amount of macrophage inflammatory protein-1alpha, CCL3, required to induce CD11b upregulation. Analysis of vital signs indicated no consistent clinical effects, and statistical analysis of ECG characteristics demonstrated no significant prolongation of the corrected QT interval. A drug-drug interaction study with ciclosporin demonstrated that CP-481,715 clearance was decreased by ciclosporin, consistent with its ability to compete with P-glycoprotein. Phase II studies may be warranted to see if CP-481,715 exhibits efficacy in treating inflammatory diseases such as rheumatoid arthritis, multiple sclerosis or transplant rejection.

The AAPS Journal, 2009

Pharmacokinetic drug interactions can lead to serious adverse events, and the evaluation of a new... more Pharmacokinetic drug interactions can lead to serious adverse events, and the evaluation of a new molecular entity's drug-drug interaction potential is an integral part of drug development and regulatory review prior to its market approval. Alteration of enzyme and/or transporter activities involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by other concomitant drugs may lead to a change in exposure leading to altered response (safety or efficacy). Over the years, various in vitro methodologies have been developed to predict drug interaction potential in vivo. In vitro study has become a critical first step in the assessment of drug interactions. Well-executed in vitro studies can be used as a screening tool for the need for further in vivo assessment and can provide the basis for the design of subsequent in vivo drug interaction studies. Besides in vitro experiments, in silico modeling and simulation may also assist in the prediction of drug interactions. The recent FDA draft drug interaction guidance highlighted the in vitro models and criteria that may be used to guide further in vivo drug interaction studies and to construct informative labeling. This report summarizes critical elements in the in vitro evaluation of drug interaction potential during drug development and uses a case study to highlight the impact of in vitro information on drug labeling.