Browsing by Author "Huang, Wei"
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- Assembly of Bio-Nanoparticles for Double Controlled Drug ReleaseHuang, Wei; Zhang, Jianfei; Dorn, Harry C.; Zhang, Chenming (PLOS, 2013-09-06)A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1) the broad final in vivo distribution of the administrated nanoparticles, and (2) strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes.
- Assembly, characterization and evaluation of a 3rd generation nanoparticle based drug carrier for metastatic breast cancer treatmentHuang, Wei (Virginia Tech, 2013-06-03)Cancer is one of the leading causes of death in the world. For women in the U.S. and the European countries, breast cancer is the most common type and it continuously threatens the lives of the patients and causes huge economic losses. Chemotherapy and endocrine therapy are the common treatments for recurrence prevention and metastatic cancer symptom palliation. However, the uses of these therapies are meanwhile largely limited because their toxic side effects and non-specificity usually lead to low quality lives of the patients. Low aqueous solubility, multi-drug resistance, degradation of drug, limited intra-tumor diffusion and etc. are other limitations of conventional chemotherapies and endocrine therapies. Nanoparticle based drug carriers were extensively studied for therapeutic drug delivery. Many carriers could be loaded with high dose of hydrophobic and hydrophilic drugs, protect the drug from the surrounding in vivo environment during the transportation, specifically target and enter the tumor cells and slowly release the drug thereafter. Advanced nanoparticle drug carriers are studied driven by the need of a more efficient drug delivery. The 3rd generation of nanoparticle based drug carriers are recently developed. They usually consist of more than one type of nanoparticles. Different part of the particle has more specialized functions. Therefore, by carefully selecting from the conventional nanoparticle carriers, a 3rd generation particle could have the properties such as high loading capacity of multiple drugs, prolonged half-life in circulation, higher tendency of accumulating at the tumor site, improved specificity to the tumor cells, higher cell uptake rate and accurately triggered controlled release, and combination of the above-mentioned properties. In our study, a paclitaxel loaded nanoparticle supported immunoliposome was assembled for metastatic breast cancer drug delivery. Functionalized single walled carbon nanohorn or poly(lactic-co-glycolic acid) was encapsulated in the polyethylene glycol (PEG) coated liposome for high drug loading and controlled release. Anti-Her2 antibody or Herceptin® was grafted onto the surface of the liposome for a higher affinity to the Her2 overexpressing breast cancer cells. Firstly, the conjugation of protein to the surface of liposome and PEGylated liposomes were investigated. Proteins with or without membrane binding domain were conjugated to liposome and PEGylated liposomes through covalent and non-covalent binding for comparison. A modified enzyme-linked immune sorbent assay was developed for surface grafted protein quantification. Secondly, the encapsulation of solid nanoparticle into PEGylated immunoliposome was investigated. Results showed a new structure of solid nanoparticle in PEGylated immunoliposome at a 1:1 ratio was formed during the repeated freeze-thawing process. Supported immunoliposomes with high homogeneity in size and structure were purified by sucrose density gradient centrifugation. Thirdly, the drug loading, triggered release, cell binding, cell uptake and cell toxicities of the supported immunoliposome were studied. Release results showed a minimum drug leakage in serum at body temperature from the particle. The release was initiated with a minor burst trigged by low pH inside the tumor cell and followed with a long term linear pattern. Cell assay results showed the highest binding affinity of the antibody or Herceptin® grafted nanoparticles to Her2 overexpressing cell lines and a lysosomal intracellular distribution of the endocytosised particles. In the final study, a fabrication process for polymeric material nanoparticles was established. The process was capable of providing accurate control of the particle size with significant high output rates, thus largely extends the scope of materials for supporting the immunoliposome.
- Compensator design for a system of two connected beamsHuang, Wei (Virginia Tech, 1994-08-05)The goal of this paper is to study the LQG problem for a class of infinite dimensional systems. We investigate the convergence of compensator gains for such systems when standard finite element schemes are used to discretize the problem. We are particularly interested in the analysis of the uniformly exponential stability of the corresponding closed - loop systems resulting from the finite dimensional compensators. A specific multiple component flexible structure is used to focus the analysis and to test problem in numerical simulations. An abstract framework for analysis and approximation of the corresponding dynamics system is developed and used to design finite - dimensional compensators. Linear semigroup theory is used to establish that the systems are well posed and to prove the convergence of generic approximation schemes. Approximate solutions of the optimal regulator and optimal observer are constructed via Galerkin - type approximations. Convergence of the scheme is established and numerical results are presented to illustrate the method
- Environmental Impacts of Foreign Direct Investment in the Pearl River DeltaHuang, Wei (Virginia Tech, 2002-04-23)The paper is aimed to trace and explain the relationship between foreign direct investment (FDI) and local natural environment changes in the Pearl River Delta (PRD). The purpose is threefold: to make a connection between the environmental problems and global economic forces; develop a model to identify if FDI is one of the major cause of the environmental changes in the PRD; and identify how FDI interacts with the local environmental policy-making process. The study reviews a wide range of literature on China¡¯s and international economic and environmental development. A tentative model is built based on existing theoretical frameworks to present the complex relationship between FDI and environment, followed by two case studies on Guangzhou and Dongguan, two cities in the PRD of different development patterns. Although FDI acts as the major economic catalyst in the region, my analysis does not show a linear relationship of FDI and environmental pollution. However, positive relationship among government regulations, FDI, and environment can be established to achieve sustainable development.
- Measuring and Modeling On-chip Interconnect Power on Real HardwareAdhinarayanan, Vignesh; Paul, Indrani; Greathouse, Joseph L.; Huang, Wei; Pattnaik, Ashutosh; Feng, Wu-chun (IEEE, 2016-09-26)On-chip data movement is a major source of power consumption in modern processors, and future technology nodes will exacerbate this problem. Properly understanding the power that applications expend moving data is vital for inventing mitigation strategies. Previous studies combined data movement energy, which is required to move information across the chip, with data access energy, which is used to read or write on- chip memories. This combination can hide the severity of the problem, as memories and interconnects will scale differently to future technology nodes. Thus, increasing the fidelity of our energy measurements is of paramount concern. We propose to use physical data movement distance as a mechanism for separating movement energy from access energy. We then use this mechanism to design microbenchmarks to ascertain data movement energy on a real modern processor. Using these microbenchmarks, we study the following parameters that affect interconnect power: (i) distance, (ii) interconnect bandwidth, (iii) toggle rate, and (iv) voltage and frequency. We conduct our study on an AMD GPU built in 28nm technology and validate our results against industrial estimates for energy/bit/millimeter. We then construct an empirical model based on our characterization and use it to evaluate the interconnect power of 22 real-world applications. We show that up to 14% of the dynamic power in some applications can be consumed by the interconnect and present a range of mitigation strategies.
- The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a modelChen, Holly Y.; Ma, Suk Ling; Huang, Wei; Ji, Lindan; Leung, Vincent H. K.; Jiang, Honglin; Yao, Xiaoqiang; Tang, Nelson L. S. (Springer Nature, 2016-12-02)Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription. An inverse correlation between the number of repeats and the extent of transactivation was found in a haplotype consisting of three promoter SNPs (C-STR-T-T). We showed that these adjacent SNPs located outside the STR were required for the STR to function as eSTR. The C allele of rs35767 provides a binding site for CCAAT/enhancer-binding-protein delta (C/EBPD), which is essential for the gradational transactivation property of eSTR and FOXA3 may also be involved. Therefore, we propose a mechanism in which the gradational transactivation by the eSTR is caused by the interaction of one or more transcriptional complexes located outside the STR, rather than by direct binding to a repeat motif of the STR.
- Stereoselective photoredox ring-opening polymerization of O-carboxyanhydridesFeng, Quanyou; Yang, Lei; Zhong, Yongliang; Guo, Dong; Liu, Guoliang; Xie, Linghai; Huang, Wei; Tong, Rong (Nature, 2018-04-19)Biodegradable polyesters with various tacticities have been synthesized by means of stereoselective ring-opening polymerization of racemic lactide and β-lactones but with limited side-chain groups. However, stereoselective synthesis of functional polyesters remains challenging from O-carboxyanhydrides that have abundant pendant side-chain functional groups. Herein we report a powerful strategy to synthesize stereoblock polyesters by stereoselective ring-opening polymerization of racemic O-carboxyanhydrides with the use of photoredox Ni/Ir catalysts and a selected Zn complex with an achiral ligand. The obtained stereoblock copolymers are highly isotactic with high molecular weights ( > 70 kDa) and narrow molecular weight distributions (Mw/Mn < 1.1), and they display distinct melting temperatures that are similar to their stereocomplex counterparts. Furthermore, in one-pot photoredox copolymerization of two different O-carboxyanhydrides, the use of such Zn complex mediates kinetic resolution of the comonomers during enchainment and shows a chirality preference that allows for the synthesis of gradient copolymers.