High-accuracy Thermal-conductivity Characterisation of Thin-film/Substrate Systems and Interfaces by Modified 3-Omega Method

Temperature rise in electronic devices due to self-heating is a major barrier to increasing the capacity of devices because higher temperatures greatly deteriorate performance reliability. The primary cause of this temperature rise is the interface thermal resistance between a thin film and a substrate. Thus, the actual temperature rise in a thin-film electronic device such as a high-performance chip is a great deal more significant than the theoretical predictions made for that device because existing theory does not integrate atomic defects and interface thermal resistance. In contrast, measuring thermal conductivity in thin crystalline specimens by using the conventional three-omega (3ω) method is challenging because controlling the heat-penetration depth is a more difficult in high thermal-conductivity crystalline materials since the heat penetrates more rapidly into specimens. This thesis develops a modified 3ω method for characterising high thermal-conductivity crystalline thin-film/substrate systems and interfaces by extending the conventional 3ω method. This research makes several contributions: First, it offers a thorough investigation of one- and two-dimensional theoretical and numerical analyses of heat conduction in a multilayered medium conducted by Joule heating a metal strip. The effect of the metal-strip width on the measurement accuracy of the 3ω method was explored. It was found that the thermal conductivity measurement can be performed over a wide range of frequencies only if the width of the metal-strip element is small relative to the film thickness. Therefore, a modified 3ω method was established. Second, experimental verifications of the theoretical investigations for the implementation of the modified 3ω method were systematically conducted. An extremely narrow and long nanostrip (height × width × length = 100 nm × 400 nm × 4 mm) was deposited on the specimen s surface using electron-beam lithography (EBL) and physical vapour deposition (PVD) techniques. Utilising the modified 3ω method, the thermal conductivity of bulk silicon (Si) wafers was successfully characterised. Third, it was discovered that the heat-penetration depth into a thin-film specimen is controllable by varying the applied current frequency, and this was performed by investigating its thermal conductivity using the modified 3ω method. The nanostrip enables the heat penetration to be as shallow as tens of microns, which is not achievable by the conventional 3ω method. In addition, the method is applied on an aluminium nitride (AlN) thin film on Si substrate, which is a commonly used thin-film/substrate system in semiconductor manufacturing devices. Fourth, the interface thermal resistance in multilayered thin-film/substrate systems were conveniently and accurately obtained by coupling theoretical predictions and experimental measurements. Specific case studies on silicon and AlN thin films on Si substrates were conducted to verify the reliability of the method. It was demonstrated that the thermal conductivity of the interface material can be obtained by the modified 3ω method in conjunction with high-resolution transmission electron microscopy (TEM). In addition, interface thermal resistance between the nanostrip material and the silicon surface and/or between the thin-film materials (i.e. Si and AlN) and the silicon substrate can be determined by the modified 3ω method. The research concluded that the method developed is applicable to the characterisation of a wide range of thin-film/substrate systems in the semiconductor industry, and that this method can be used to optimise the crystalline thin film on substrate designs aimed at improving overall thermal conductivity and therefore device efficiency

Chemical Constituents of Dichloromethane Extract of Cultivated Satureja khuzistanica

Four compounds β-sitosterol, β-sitosterol-3-O-β-d-glucopyranoside, ursolic acid and 4′,5,6-trihydroxy-3′, 7-dimethoxyflavone were characterized from the dichloromethane extract of the aerial parts of Satureja khuzistanica (Lamiaceae), a native medicinal plant growing in Iran, on the basis of spectral analysis and comparing with the data in literature. The natural occurrence of these compounds can be conclusive for the chemotaxonomic characterization of the genus Satureja

Integrating Molecular Networking and 1H NMR Spectroscopy for Isolation of Bioactive Metabolites from the Persian Gulf Sponge Axinella sinoxea

The geographic position, highly fluctuating sea temperatures and hypersalinity make Persian Gulf an extreme environment. Although this unique environment has high biodiversity dominated by invertebrates, its potential in marine biodiscovery has largely remained untapped. Herein, we aimed at a detailed analysis of the metabolome and bioactivity profiles of the marine sponge Axinella sinoxea collected from the northeast coast of the Persian Gulf in Iran. The crude extract and its Kupchan subextracts were tested in multiple in-house bioassays, and the crude extract and its CHCl3-soluble portion showed in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium (Efm). A molecular networking (MN)-based dereplication strategy by UPLC-MS/MS revealed the presence of phospholipids and steroids, while 1H NMR spectroscopy indicated the presence of additional metabolites, such as diketopiperazines (DKPs). Integrated MN and 1H NMR analyses on both the crude and CHCl3 extracts combined with an antibacterial activity-guided isolation approach afforded eight metabolites: a new diketopiperazine, (-)-cyclo(L-trans-Hyp-L-Ile) (8); a known diketopiperazine, cyclo(L-trans-Hyp-L-Phe) (7); two known phospholipids, 1-O-hexadecyl-sn-glycero-3-phosphocholine (1) and 1-O-octadecanoyl-sn-glycero-3-phosphocholine (2); two known steroids, 3β-hydroxycholest-5-ene-7,24-dione (3) and (22E)-3β-hydroxycholesta-5,22-diene-7,24-dione (4); two known monoterpenes, loliolide (5) and 5-epi-loliolide (6). The chemical structures of the isolates were elucidated by a combination of NMR spectroscopy, HRMS and [α]D analyses. All compounds were tested against MRSA and Efm, and compound 3 showed moderate antibacterial activity against MRSA (IC50 value 70 μg/mL). This is the first study that has dealt with chemical and bioactivity profiling of A. sinoxea leading to isolation and characterization of pure sponge metabolites

Hypermongone C Accelerates Wound Healing through the Modulation of Inflammatory Factors and Promotion of Fibroblast Migration

The physiology of wound healing is dependent on the crosstalk between inflammatory mediators and cellular components of skin regeneration including fibroblasts and endothelial cells. Therefore, strategies to promote healing must regulate this crosstalk to achieve maximum efficacy. In light of the remarkable potential of natural compounds to target multiple signaling mechanisms, this study aims to demonstrate the potential of hypermongone C, a polycyclic polyprenylated acylphloroglucinol (PPAP), to accelerate wound closure by concurrently enhancing fibroblast proliferation and migration, promoting angiogenesis, and suppressing pro-inflammatory cytokines. This compound belongs to a family of plants (Hypericum) that traditionally have been used to treat injuries. Nevertheless, the exact biological evidence to support the claims is still missing. The results were obtained using a traditional model of cell scratch assay and endothelial cell tube formation, combined with the analysis of protein and gene expression by macrophages. In summary, the data suggest that hypermongone C is a multi-targeting therapeutic natural compound for the promotion of tissue repair and the regulation of inflammation

Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-β-Rhamnoside Isolated from Parrotia persica

Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-β-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-β-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-β-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-β-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-β-rhamnoside and chlorogenic acid

7-epi-Clusianone, a Multi-Targeting Natural Product with Potential Chemotherapeutic, Immune-Modulating, and Anti-Angiogenic Properties

Targeted therapies have changed the treatment of cancer, giving new hope to many patients in recent years. The shortcomings of targeted therapies including acquired resistance, limited susceptible patients, high cost, and high toxicities, have led to the necessity of combining these therapies with other targeted or chemotherapeutic treatments. Natural products are uniquely capable of synergizing with targeted and non-targeted anticancer regimens due to their ability to affect multiple cellular pathways simultaneously. Compounds which provide an additive effect to the often combined immune therapies and cytotoxic chemotherapies, are exceedingly rare. These compounds would however provide a strengthening bridge between the two treatment modalities, increasing their effectiveness and improving patient prognoses. In this study, 7-epi-clusianone was investigated for its anticancer properties. While previous studies have suggested clusianone and its conformational isomers, including 7-epi-clusianone, are chemotherapeutic, few cancer types have been demonstrated to exhibit sensitivity to these compounds and little is known about the mechanism. In this study, 7-epi-clusianone was shown to inhibit the growth of 60 cancer cell types and induce significant cell death in 25 cancer cell lines, while simultaneously modulating the immune system, inhibiting angiogenesis, and inhibiting cancer cell invasion, making it a promising lead compound for cancer drug discovery