Studies on the Role of Interleukin-6 in Prostate Cancer Development and in the Induction of Chronic Prostatic Inflammation by Propionibacterium acnes

Prostate cancer is one of the most common cancers in men worldwide. Inflammation is commonly observed in prostatic tissues, and correlative studies suggest that the inflammatory cytokine interleukin-6 (IL-6) may contribute to prostate carcinogenesis. However, the source of IL-6 production in the prostate tumor microenvironment has yet to be determined. In this thesis project, the cellular origin of IL-6 in both primary and metastatic prostate cancer was examined by a novel chromogenic in situ hybridization (CISH) assay. These studies indicated that, contrary to previously published studies, neither primary nor metastatic prostate adenocarcinoma cells express IL-6 mRNA. In contrast, IL-6 expression was very heterogeneous, nearly exclusively restricted to the prostate stromal compartment, and enriched in areas of acute inflammation. In metastatic disease, tumor cells were negative in all lesions and IL-6 expression was restricted to endothelial cells within the vasculature of bone metastases. We further report initial evidence that IL-6 may be involved in prostate tumor growth as evidenced by a series of allograft studies in C57BL/6J wildtype and IL-6 knockout (IL6-/-) mice. Compared to wildtype mice, IL6-/- mice had a significant reduction in take rate and tumor size of allografts of the TRAMP-C2 prostate tumor cell line. This trend was not observed for the colon MC38 cell line. Interestingly, IL-6 ELISA analyses showed a significant increase in circulating IL-6 levels in mice with TRAMP-C2 tumors. We then turned to a mouse model to further study the role of IL-6 in inducing and/or sustaining long-term chronic inflammation in the mouse prostate, as accumulating evidence indicates that this may be an important factor in the early development of prostate cancer. For these studies we aimed to use a clinically relevant human-derived strain of bacteria to induce inflammation in the mouse prostate. We cultured tissues from a series of radical prostatectomy specimens and found that the pro-inflammatory anaerobe Propionibacterium acnes (P. acnes) can be readily cultured from these tissues. Cultured P. acnes isolates were typed using multilocus sequence typing (MLST), the results of which suggested that prostatectomy-derived P. acnes isolates are not simply the result of contamination from skin flora. These data, along with studies in wildtype mice indicating that one of the strains of P. acnes (PA-2) can induce long-term prostatic inflammation, suggest that this is a clinically relevant species to study. We inoculated IL6-/- mice with the prostate derived PA-2 P. acnes and found that unlike wildtype mice that develop chronic inflammation that persists up to a year post-inoculation, mice with IL-6 depletion did not sustain chronic inflammation beyond a 2 month time point. In summary, in this thesis we aimed to examine the many possible roles of IL-6 in prostate cancer development and progression. We determined that paracrine rather than autocrine IL-6 production is likely associated with any role for the cytokine in prostate cancer progression. Furthermore, we report that systemic IL-6 levels may play a role in prostate tumor growth and that IL-6 could also be involved in the development of long-term bacteria-induced chronic inflammation in the prostate

On the local aspect of valleytronics

Valley magnetic moments play a crucial role in valleytronics in 2D hexagonal materials. Traditionally, based on studies of quantum states in homogeneous bulks, it is widely believed that only materials with broken structural inversion symmetry can exhibit nonvanishing valley magnetic moments. Such constraint excludes from relevant applications those with inversion symmetry, as specifically exemplified by gapless monolayer graphene despite its technological advantage in routine growth and production. This work revisits valley-derived magnetic moments in a broad context covering inhomogeneous structures as well. It generalizes the notion of valley magnetic moment for a state from an integrated total quantity to the local field called "local valley magnetic moment" with space-varying distribution. In suitable inversion-symmetric structures with inhomogeneity, e.g., zigzag nanoribbons of gapless monolayer graphene, it is shown that the local moment of a state can be nonvanishing with sizable magnitude, while the corresponding total moment is subject to the broken symmetry constraint. Moreover, it is demonstrated that such local moment can interact with space-dependent electric and magnetic fields manifesting pronounced field effects and making possible a local valley control with external fields. Overall, a path to "local valleytronics" is illustrated which exploits local valley magnetic moments for device applications, relaxes the broken symmetry constraint on materials, and expands flexibility in the implementation of valleytronics

Experimental study on the validity of flow region division

Einstein first proposed that a river flow can be divided into three parts, corresponding to the banks and its bed, respectively, but he did not explain why the flow is dividable and how to divide the flow, in other words the flow division is only a mathematical treatment to simplify his analysis. Since Einstein\u27s proposition there have been many researches and debates on this topic, many division lines have been proposed, but there is no specially designed experimental research to verify the physical existence of division lines, and these division lines have not been tested against the experimental data. For this purpose, an experiment in a rectangular open channel was conducted to measure whether zero-shear stress exists in an open channel except its existence on the free surface. The measured results reveal that zero-shear stress indeed exists below the free surface, and some proposed equations of division line agree well with the profile of the measured zero-shear line, thus it is clarified that Einstein\u27s hypothesis is not only useful to simplify the mathematical treatment, but also it has the physical basis, i.e., zero-shear division line. As far as the authors know, in the literature, this is the first experimental proof that the division lines indeed exist in channel flows

Experimental study on flow resistance over rigid vegetated channel

Vegetation is an important part of the ecological channel, and flow structure over vegetation in ecological channel is rather complex. The vegetation resistance to flow is affected by many factors, and there is still no general calculation method to express it. Thus, it is necessary to explore the mechanism of flow resistance over vegetation in open channel. In this paper, the rigid cylindrical sticks arranged in the open channel were used to simulate the stems of non-submerged vegetation in order to investigate the effects of vegetation on the flow. Through theoretical analysis and experimental verification, it shows the form drag caused by vegetation is closely related to the vortex volume created by vegetation. In addition, the total resistance of vegetated channel can be determined by two methods based on vegetation density and flow resistance partitioning, respectively, and both of them are verified by the experimental results. What\u27s more, for rigid vegetation, the drag coefficient is closely related to vegetation density, spacing between vegetation patches and the Reynolds number. The empirical formula among them was established through the experimental results

4-Methyl-2-oxo-2,3-dihydro-1-benzopyran-7-yl benzene­sulfonate

The title compound, C16H12O5S, is a derivative of coumarin. The dihedral angle between the coumarin ring system and the phenyl ring is 65.9 (1)°. In the crystal structure, mol­ecules are linked by weak C—H⋯O hydrogen bonding to form molecular ribbons

A Community-Based Walk-In Screening of Depression in Taiwan

Depression is a crucial public health problem because of its relatively high association with suicidal attempts, prolonged social isolation, poor physical health, and dementia. However, the available data and study on the prevalence of depression in Taiwan were mostly completed within the previous 1 to 2 decades, and these studies were limited to certain areas or populations. Little is known regarding the current status of depression in Taiwan. We used a brief tool, the Center for Epidemiological Studies Depression Scale (CES-D), to screen depression in 4 areas among the general and aged population. The results showed a higher CES-D score in the southern area among general (mean ± SD: 7.8 ± 8.4) or aged participants (mean ± SD: 7.2 ± 8.0) compared with other areas. The ratio of suspected depression patients was 16.4% of all recruited participants and 13.3% of aged participants. These results may provide information for this public health issue

The top quark rare decays with flavor violation

In the present study, we investigate the decays of the top quark $t\rightarrow c\gamma$, $t\rightarrow cg$, $t\rightarrow cZ$ and $t\rightarrow ch$. They are extremely rare processes in the Standard Model (SM). As the $U(1)_X$ extension of the minimal supersymmetric standard model, the $U(1)_X$SSM features new superfields such as the right-handed neutrinos and three Higgs singlet states. We analyze the effects of different sensitivity parameters on the results and make reasonable theorecial predictions useful for future experimental developments. Considering the constraint of the updated experimental data, the numerical results show that the branching ratios of all four processes $t\rightarrow c\gamma,~cg,~cZ,~ch$ can reach the same order of magnitude as their experimental upper limits. Among them, $\tan\beta$ has the most obvious effect on each process and is the main parameter. $g_X$, $g_{YX}$, $\mu$, $M_2$, $\lambda_H$, $M_{U23}^2$ and $M_{Q23}^2$ are important parameters for the processes, and have effects on the numerical results.Comment: pages 22, figures 1