| 1. |
- Zhao, Jie
(författare)
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Solution-Processable Conductive Graphene-Based Materials for Flexible Electronics
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis work explores electrical conductors based on few-layer graphene flakes as an enabler for low-cost, mechanically flexible, and high-conductivity conductors in large area flexible and printed electronic devices. The flakes are deposited from aqueous solutions and processed at low temperature.Graphene is selected for its excellent properties in mechanical, optical, electronic, and electrical aspects. However, thin films of pristine few-layer graphene flakes deposited from dispersions normally exhibit inferior electrical conductivity. One cause responsible for this problem is the loose stacking and random orientation of graphene flakes in a graphene deposition. We have solved this problem by implementing a simple post-deposition treatment leading to dramatically densified and planarized thin films. Significantly increased electrical conductivity by ~20 times is obtained. The 1-pyrenebutyric acid tetrabutylammonium salt as an exfoliation enhancer and dispersant in water yields ~110 S/m in conductivity when the graphene based thin films are processed at 90 °C. In order to achieve higher conductivity, a room-temperature method for site-selective copper electroless deposition has been developed. This method is of particular interest for the self-aligned copper deposition to the predefined graphene films. The resultant two-layer graphene/copper structure is characterized by an overall conductivity of ~7.9 × 105 S/m, an increase by ~7000 times from the template graphene films. Several electronic circuits based on the graphene/copper bilayer interconnect have been subsequently fabricated on plastic foils as proof-of-concept demonstrators. Alternatively, highly conductive composites featuring graphene flakes coated with silver nanoparticles with electrical conductivity beyond 106 S/m can be readily obtained at 100 oC. Moreover, a highly conductive reduced-graphene-oxide/copper hybrid hydrogel has been achieved by mixing aqueous graphene oxide solution and copper-containing Fehling's solution. The corresponding aerogel of high porosity exhibits an apparent electrical conductivity of ~430 S/m and delivers a specific capacity of ~453 mAh g−1 at current density of 1 A/g. The experimental results presented in this thesis show that the solution-phase, low-temperature fabrication of highly conductive graphene-based materials holds promises for flexible electronics and energy storage applications.
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| 2. |
- He, Jie
(författare)
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Gasification-based Biorefinery for Mechanical Pulp Mills
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The modern concept of “biorefinery” is dominantly based on chemical pulp mills to create more value than cellulose pulp fibres, and energy from the dissolved lignins and hemicelluloses. This concept is characterized by the conversion of biomass into various bio-based products. It includes thermochemical processes such as gasification and fast pyrolysis. In thermo-mechanical pulp (TMP) mills, the feedstock available to the gasification-based biorefinery is significant, including logging residues, bark, fibre material rejects, bio-sludges and other available fuels such as peat, recycled wood and paper products. On the other hand, mechanical pulping processes consume a great amount of electricity, which may account for up to 40% of the total pulp production cost. The huge amount of purchased electricity can be compensated for by self-production of electricity from gasification, or the involved cost can be compensated for by extra revenue from bio-transport fuel production. This work is to study co-production of bio-automotive fuels, bio-power, and steam via gasification of the waste biomass streams in the context of the mechanical pulp industry. Ethanol and substitute natural gas (SNG) are chosen to be the bio-transport fuels in the study. The production processes of biomass-to-ethanol, SNG, together with heat and power, are simulated with Aspen Plus. Based on the model, the techno-economic analysis is made to evaluate the profitability of bio-transport fuel production when the process is integrated into a TMP mill.The mathematical modelling starts from biomass gasification. Dual fluidized bed gasifier (DFBG) is chosen for syngas production. From the model, the yield and composition of the syngas and the contents of tar and char can be calculated. The model has been evaluated against the experimental results measured on a 150KWth Mid Sweden University (MIUN) DFBG. As a reasonable result, the tar content in the syngas decreases with the gasification temperature and the steam to biomass (S/B) ratio. The biomass moisture content is a key parameter for a DFBG to be operated and maintained at a high gasification temperature. The model suggests that it is difficult to keep the gasification temperature above 850 ℃ when the biomass moisture content is higher than 15.0 wt.%. Thus, a certain amount of biomass or product gas needs to be added in the combustor to provide sufficient heat for biomass devolatilization and steam reforming.For ethanol production, a stand-alone thermo-chemical process is designed and simulated. The techno-economic assessment is made in terms of ethanol yield, synthesis selectivity, carbon and CO conversion efficiencies, and ethanol production cost. The calculated results show that major contributions to the production cost are from biomass feedstock and syngas cleaning. A biomass-to-ethanol plant should be built over 200 MW.In TMP mills, wood and biomass residues are commonly utilized for electricity and steam production through an associated CHP plant. This CHP plant is here designed to be replaced by a biomass-integrated gasification combined cycle (BIGCC) plant or a biomass-to-SNG (BtSNG) plant including an associated heat & power centre. Implementing BIGCC/BtSNG in a mechanical pulp production line might improve the profitability of a TMP mill and also help to commercialize the BIGCC/BtSNG technologies by taking into account of some key issues such as, biomass availability, heat utilization etc.. In this work, the mathematical models of TMP+BIGCC and TMP+BtSNG are respectively built up to study three cases: 1) scaling of the TMP+BtSNG mill (or adding more forest biomass logging residues in the gasifier for TMP+BIGCC); 2) adding the reject fibres in the gasifier; 3) decreasing the TMP SEC by up to 50%.The profitability from the TMP+BtSNG mill is analyzed in comparison with the TMP+BIGCC mill. As a major conclusion, the scale of the TMP+BIGCC/BtSNG mill, the prices of electricity and SNG are three strong factors for the implementation of BIGCC/BtSNG in a TMP mill. A BtSNG plant associated to a TMP mill should be built in a scale above 100 MW in biomass thermal input. Comparing to the case of TMP+BIGCC, the NR and IRR of TMP+BtSNG are much lower. Political instruments to support commercialization of bio-transport fuel are necessary.
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| 3. |
- Zhang, Jie
(författare)
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A numerical model to simulate short-term beach and dune evolution
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sediment transport in the cross-shore (CS) and associated changes in the beach profile, especially during storms, have been topics of widespread concern. Since storms are often accompanied by high water levels and large waves, large quantities of sand from the beach and the dune are typically transported offshore, leading to severe beach and dune erosion, which threatens the integrity of buildings and infrastructure near the coast. With climate change, sea levels are expected to rise and storms are likely to grow in numbers and intensity, which further aggravates coastal flooding and erosion. The capability to quantify storm impact on the beach and dune is becoming increasingly important both for coastal engineers and managers. Thus, in this thesis, a new numerical model to simulate hydrodynamics, CS sediment transport, as well as beach and dune evolution under varying waves and water levels was developed. Particular focus was put on describing the response of the subaerial region of the profile, involving the foreshore, the berm, and the dune. A variety of modules, involving wave transformation, CS currents, mean water elevation, and CS sediment transport across the profile, by including relevant physics in combination with a set of theoretical and empirical formulas were included in the model. The theory employed in the new model was first calibrated and validated against data from the SUPERTANK laboratory, where the experimental cases selected encompassed several types of profile evolution, including berm erosion and bar formation, berm flooding and erosion, and offshore mound evolution. Good agreement was obtained between calculations and measurements, indicating that the model can produce robust and reliable predictions of CS transport and profile evolution in the nearshore. Then, the model was applied to two field sites, Cocoa Beach and Perdido Key Beach in Florida, USA, to simulate the evolution of a mound placed in the offshore exposed to varying non-breaking waves and water levels. In addition, several scenarios with different mound volume and location designs were investigated to indicate potential uses for the model. The results illustrate that the model can be used for providing guidance to the design of mounds in the offshore that is of great value in coastal planning and management, especially for beach nourishment. Finally, the model was applied to simulate the dune erosion during storms, where the wave impact theory was used for describing the impact of waves on the dune. Both laboratory data and field data were used for model testing. The results indicated that the model could reproduce the dune retreat rather well. Overall, the new numerical model could be a useful tool in practical engineering projects for predicting CS sediment transport and beach and dune profile evolution.
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| 4. |
- Zhang, Jie
(författare)
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CVD growth and material quality control of silicon carbide
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- SiC has emerged as a promising semiconductor to replace Si in high power, high frequency and high temperature electronics. Thanks 1to the advantageous intrinsic material properties, such as large band gap, high electric breakdown field, high thermal conductivity and highly inert chemical properties, intensified efforts world-wide have been attracted in developing crystal growth technology and device fabrication processes for the SiC components. As a result of the fast progress in the crystal growth technology, up to 3 inch n-type and 2 inch both n- and p-type SiC substrates, grown by seeded sublimation technique, are now commercially available. The substrate quality is under constant improvement in terms of micropipe density and structural perfection. In this context, a new crystal growth technique using high temperature chemical vapour deposition (HTCVD) has accelerated the improvement of substrate quality and demonstrated great potential for producing high quality semi-insulating SiC substrates.For SiC device fabrication, CVD has been the technique of choice for producing epitaxial structures. For kV-class high power devices, thick and low-doped epilayers with high crystalline quality are required. To meet this requirement, a fast epitaxy technique has been developed in a vertical, hot-wall reactor, also known as a chimney reactor. Compared with the growth rate of 2 - 6 μm/h from the convention CVD in the horizontal hot-wall reactor, the chimney process has produced epilayers with growth rates as high as 10 - 40 μm/h and residual doping of low 1013 - 10 15 cm-3 • Edge-terminated Schottky diodes made on the chimney-grown epilayers have demonstrated a reverse blocking voltage of 3.85 kV. The system design concern of the chimney reactor and the characteristics of the fast epitaxy technique are presented in Paper 1. The growth behaviour in the vertical hot-wall reactor in both up- and down-orientations is further exploited in Paper 2. The nitrogen doping behaviour and the morphology control of the thick epilayers are investigated in Papers 3 and 4. In paper 5, the electrically active impurities in these epilayers are characterised using Deep Level Transient Spectrometry (DLTS). The influence of the growth conditions on these defects is studied. For low-power or high frequency devices such as MESFETs, the CVD process developed in a horizontal hot-wall reactor has shown to be capable of matching the specific demands imposed by these devices. During the process development in this reactor, the pre-growth etching of the substrate has shown to improve the morphology of the subsequently grown epilayers. A detailed study of the in situ etching mechanism has been carried out and the results are presented in Paper 6. To significantly increase the uniformity and the throughput, gas foil rotation has been installed in this reactor, providing a capacity of 3x2" wafers. The first results of the epilayers grown with the gas foil rotation in the horizontal hot-wall CVD reactor is reported in Paper 7.
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| 5. |
- Zhang, Jie, 1981
(författare)
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Global Regulation of Snf1 in Saccharomyces cerevisiae: A case study of experimental systems biology
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cells commonly face environmental changes and have evolved various regulatory mechanisms to adjust their metabolism accordingly. One such key regulator in S. cerevisiae is the Snf1 kinase, which belongs to the conserved AMP-activated protein kinase (AMPK) family in all eukaryotes. The main function of Snf1 is to sense the energetic status in the cell and switch the cell metabolism from anabolism to catabolism through a complex regulatory network. In this study, we applied an experimental systems biology approach to study the regulation of Snf1 in S. cerevisiae at the global level. First, we show that the three β-subunits of Snf1 (Sip1, Sip2 and Gal83) are not redundant and found that Sip2, but not Sip1, can take over in the utilization of ethanol and glycerol when Gal83 is deleted, although both Sip1 and Sip2 isoforms can utilize acetate as the carbon source. To map the possible protein interactions of Snf1 with TORC1, a key regulator in the nitrogen catabolite repression (NCR), we assessed the global effect of deleting Snf1 and/or Tor1 under nutrient limited conditions. We show that Snf1 may regulate amino acid biosynthesis by inducing the GDH3 encoded glutamate dehydrogenase, and therefore may represent a convergence to the TORC1 pathway. The data also suggest that Snf1 plays a larger role in the regulation of translation under the nutrient-limited conditions tested, compared to TORC1. Finally, we examined the effects of replacing the kinase domain of Snf1 with its analog from AMPK. The chimeric α1-Snf1 kinase restored the functions of Snf1, although to a lesser extent. However, this chimera fails to repress sterol biosynthesis as the native Snf1 does, and we attribute this to different phosphorylation motifs between Snf1 and AMPK. We also propose that Snf1 might repress the sterol biosynthetic genes by phosphorylating Ser272 of the transcription factor Ecm22, and therefore exerts transcriptional regulation on this process. Through these examples, we demonstrate that experimental systems biology is useful for investigating complex regulatory networks and powerful for identifying molecular targets for validation.
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| 6. |
- Zhang, Jie
(författare)
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Studies on 7a-hydroxycholesterol in extrahepatic tissues and cells
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In human liver, primary bile acids are synthesized from cholesterol via the well-established neutral and also via the recently described acidic pathways. The latter includes 27-hydroxycholesterol 7alpha-hydroxylase. Extrahepatic presence and function of this enzyme as well as the possible occurrence of other hydroxylases were investigated in the present study. For this purpose, radio-labeled 27-hydroxycholesterol (27-OHC) and 25-hydroxy-cholesterol (25-OHC) were prepared. Both hydroxysterols were 7a-hydroxylated, and subsequently oxidized to 7a-hydroxy-3-oxo-A4 steroids, in cultures of human diploid fibroblasts (HDF), rat astrocytes, Schwann cells and neurons, mouse thymic epithelial cells, and the human melanoma cell line SK-MEL-2 but not in virus-transformed fibroblasts (9OVA-VI) and the malignant cell lines WiDr and MDA-231. Some 27-OHC was also oxidized to 3beta-hydroxy-5-cholestenoic, 3beta,7alpha-dihydroxy-5-cholestenoic and 7alpha-hydroxy-3-oxo-4-cholestenoic acids. In case of 25-hydroxycholesterol, regulation of 7alpha-hydroxylation was studied and the reaction was found to be stimulated by interleukin-1beta, dexamethasone and cortisol, and inhibited by metyrapone and RU486. In healthy volunteers, the concentration of 7alpha-hydroxy-3-oxo-4-cholestenoic acid was found to be significantly higher in peripheral arterial than in hepatic venous blood, indicating an extrahepatic formation of 7alpha-hydroxylated metabolites of cholesterol in vivo. 27-Hydroxycholesterol 7alpha-hydroxylase was present in microsomal preparations from rat brain. In addition to 25-OHC and 27-OHC, 3beta-hydroxy-5-cholestenoic and 3beta-hydroxy-5-cholenoic acids, dehydroepiandrosterone (DHEA) and pregnenolone were 7alpha-hydroxylated. For 27-OHC, the apparent Km was about 2 myM and Vmax about 15 pmol/min xmg protein. Competition experiments indicated that the same enzyme 7alpha-hydroxylated 27-OHC and 25-OHC which, however, was different from cholesterol 7alpha-hydroxylase. Other extrahepatic 7alpha-hydroxylase(s) may exist. 25-Hydroxylation was found to be an important reaction in cultures of rat astrocytes and Schwann cells leading to formation of significant amounts of 7alpha,25-dihydroxy-4-cholesten-3-one. Several 7alpha-hydroxylated metabolites of 27-OHC and 25-OHC, e.g. 7alpha,25-diOHC,27-OHC, 7alpha,27-diOHC and 7alpha,27-dihydroxy-4-cholesten-3-one, were found to be as effective suppressors of HMG-CoA reductase activity in fibroblasts as 25-OHC. The suppression of this activity by 25-OHC and 27-OHC was reduced or abolished by DHEA and pregnenolone. In 90VA-VI cells, 7alpha,27-diOHC but not 7alpha,25-diOHC had suppressor activity. The results suggest that 7alpha-hydroxylation is not directly involved in the potential function of 27-OHC and 25-OHC as regulators of HMG-CoA reductase activity. Both 25-OHC and 27-OHC were inducers of apoptosis in mouse thymocytes. 7alpha-Hydroxylation of both compounds as well as formation of acidic metabolites of 27-OHC decreased or abolished the apoptotic effects, suggesting a protective role of these reactions in hydroxycholesterol-induced apoptosis.
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| 7. |
- Zhang, Jie
(författare)
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Targeting Human Epidermal Growth Factor Receptors with Drug Conjugates Based on Affibody Molecules
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is a major public health challenge and the second leading cause of death in the world, with millions of new cases being diagnosed each year. Traditional cancer treatments such as surgery, radiation therapy, and chemotherapy are many times effective, but may also cause damage to healthy cells, leading to side effects. Targeted therapy is a more precise and focused approach to cancer treatment, where the aim is to target the cancer cells while leaving the normal cells unaffected. It is particularly effective in cancers where specific molecular targets are known, such as the subset of breast cancer patients with HER2 over-expression or in the subset of patients with pancreatic cancer with HER3 over-expression. Antibody-drug conjugates (ADCs) are an important addition to tumor-targeted therapy, with twelve drugs approved for clinical use by the FDA. They utilize the high specificity of monoclonal antibodies conjugated with highly cytotoxic small molecules to enhance the accumulation of the drugs in the tumor, for highly specific and efficient killing. However, traditional ADCs may not be the optimal delivery format for the directed delivery of cytotoxic drugs. They are limited by their relatively large molecular weights, resulting in relatively low penetration of solid tumors. Recently, a novel type of drug conjugates, affibody-drug conjugates, has been described. These combined an engineered scaffold affinity protein, an affibody molecule, with an albumin binding domain (ABD) for half-life extension, to which a cytotoxic payload has been conjugated. Previous studies show that these novel drug conjugates have a potent and tumor-cell-specific cytotoxic effect. In the future, they may therefore become complementary or alternatives to current targeted cancer therapies. This thesis focuses on the optimization of affibody-drug conjugates targeting HER2 and HER3, members of the human epidermal growth factor receptor family. The thesis presents in vitro and in vivo preclinical data, showing the potential for further clinical development. In paper I, we investigated the influence of the drug-to-affibody ratio (DAR) on the pharmacokinetic profile of affibody-drug conjugates targeting HER2. Increasing the drug load resulted in an elevated delivery of the DM1 drug to the tumors; however, it also led to increased uptake by the liver. Further optimization of the molecular design is necessary to enable highly efficient delivery to tumors while minimizing the uptake in normal organs and tissues. In paper II, the effect of the length and composition of the linker between the HER2 targeting affibody molecule and the ABD was investigated. The use of a 12 amino acids linker reduced hepatic uptake compared with the use of a 5 amino acids linker. This finding offers an important insight into the influence of the linker on the properties of the affibody drug conjugates. In paper III, we investigated the influence of different cytotoxic payloads, as part of an affibody-drug conjugate targeting HER2, on binding properties, cytotoxicity, biodistribution, and anti-tumor effect. The combination of a potent cytotoxic effect in vitro, and a high tumor uptake in vivo, resulted in a superior anti-tumor effect for ZHER2- ABD-mcMMAF at lower doses compared to the previously investigated ZHER2-ABD- mcDM1. Importantly, it maintained a favorable toxicity profile with lower liver uptake compared to ZHER2-ABD-mcDM1. The affibody-drug conjugate ZHER2-ABD- mcMMAF holds great promise as a valuable agent for HER2-targeted cancer therapy. In paper IV, we generated a series of HER2-targeted affibody-drug conjugates fused with different PAS or XTEN polypeptides. We evaluated the ability of the XTEN and PAS polypeptides to extend the plasma half-life, and their influence on tumor uptake, and tissue biodistribution. We compared our new constructs with the previously developed construct, ZHER2-ABD-mcDM1, where an albumin binding domain was used for half-life extension. It was found that the ABD-fused affibody-drug conjugate demonstrated superior tumor uptake and tumor-to-normal-organ ratios compared to the PASylated and XTENylated affibody-drug conjugates. It is possible that ABD is better also for other cancer-targeting strategies where a high tumor uptake while maintaining comparable accumulation in normal tissues is desired. In paper V, we compared the binding properties and cytotoxic potential of a monovalent and a bivalent HER3-targeting affibody-drug conjugate. The biodistribution and therapeutic potential of the bivalent drug construct were evaluated. We found that the bivalent ZHER3-ABD-ZHER3- mcDM1 is a highly potent drug conjugate with favorable biodistribution and anti-tumor efficacy. These results suggest that ZHER3-ABD-ZHER3-mcDM1 holds promise for future clinical development as a potential therapeutic option for patients with HER3 over-expressing cancer. In summary, the potential for modification and optimization through the design of diverse components within HER2 and HER3-targeting affibody-drug conjugates significantly enhances therapeutic effectiveness, thereby encouraging prospective advancements in the development of targeted drug conjugates.
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