Summer Final Report

The summer of 2012 has been filled with many memorable events and activities. As an intern, I had responsibilities that had to be fulfilled. My tour of duty was completed as an administrative student trainee in the Information Technology and Communications Services Business Office (IT-A). In accordance with the Business Objectives and Agreement of the Business Office and my performance plan, I was to provide business office support, improve business, project management, and technical work processes. With this being stated, I supported a project called "The Big Move Project" (TBMP), which will take course over the next several years. The Big Move Project is the planning of the Information Technology (IT) Directorate's relocation to various buildings in the course of upcoming years, when designs and the building of Central Campus have been completed. Working directly with my supervisor and the project manager, I was responsible for gathering both administrative and operational area requirements for the Information Technology (IT) Directorate, along with its outsourced support and contractors, such as IMCS, NICS, and ACES. My first action was to create rubrics that will serve as a guideline for the information that should be given by each branch of IT. After receiving that information via a few KAITS actions, I was able to start the consolidation process, and begin working on a presentation. A SharePoint was created shortly after for others to view the progression of the project, which I managed. During the consolidation ofthis information, I would occasionally present to the IT Deputy Director and IT Chiefs. The draft of this presentation was shown to employees of Center Operations (T A) and stakeholders-IT Chief Officers and contractor managers-in the relocation of IT to make them aware of what requirements must be met that will enable IT to be accommodated appropriately in the design of Central Campus Phase 11-the time in which IT and its contractors are scheduled to be relocated. Besides supporting TBMP, I also supported the Section 508 Policy Compliance Coordinator, R. Liang. Section 508 is a policy that requires employers to implement accessibility assurance of information and technology to disabled communities. On Thursday, July 19, 2012, I was able to go to Camp Boggy Creek-a camp for disabled children-for an education outreach, in collaboration with the Education Office. We shared with them information about how astronauts live and work in space, they were able to ride hovercrafts, build paper rockets, and then launch them outside. Although this outreach was quite fun with the kids at the camp, this was a learning opportunity to gain some insight to those with cognitive and physical disabilities, the problems they typically face, and in tum, how to accommodate those with disabilities in the work environment. In the process of implementing accessibility and Section 508 compliance, I attended various teleconferences, did field runs to supply closed-caption call phones to employees with limited hearing, and helped with the development of the charter ofthe Section 508 Compliance Working Group

Mutual epithelium-macrophage dependency in liver carcinogenesis mediated by ST18

The ST18 gene has been proposed to act either as a tumor suppressor or as an oncogene in different human cancers, but direct evidence for its role in tumorigenesis has been lacking thus far. Here, we demonstrate that ST18 is critical for tumor progression and maintenance in a mouse model of liver cancer, based on oncogenic transformation and adoptive transfer of primary precursor cells (hepatoblasts). ST18 messenger RNA (mRNA) and protein were detectable neither in normal liver nor in cultured hepatoblasts, but were readily expressed after subcutaneous engraftment and tumor growth. ST18 expression in liver cells was induced by inflammatory cues, including acute or chronic inflammation in vivo, as well as coculture with macrophages in vitro. Knocking down the ST18 mRNA in transplanted hepatoblasts delayed tumor progression. Induction of ST18 knockdown in pre-established tumors caused rapid tumor involution associated with pervasive morphological changes, proliferative arrest, and apoptosis in tumor cells, as well as depletion of tumor-associated macrophages, vascular ectasia, and hemorrhage. Reciprocally, systemic depletion of macrophages in recipient animals had very similar phenotypic consequences, impairing either tumor development or maintenance, and suppressing ST18 expression in hepatoblasts. Finally, RNA sequencing of ST18-depleted tumors before involution revealed down-regulation of inflammatory response genes, pointing to the suppression of nuclear factor kappa B–dependent transcription. Conclusion: ST18 expression in epithelial cells is induced by tumor-associated macrophages, contributing to the reciprocal feed-forward loop between both cell types in liver tumorigenesis. Our findings warrant the exploration of means to interfere with ST18-dependent epithelium–macrophage interactions in a therapeutic setting. (Hepatology 2017;65:1708-1719)

Immunohistochemical analysis of development of desmin-positive hepatic stellate cells in mouse liver

Development of desmin-positive hepatic stellate cells was studied in mice using double immunofluorescent techniques and in vitro cultures with special attention given to their cell lineages. Several studies recently reported on the presence of cells that are immunologically reactive with both antidesmin and anticytokeratin antibodies in young fetal rat livers, and suggested the possibility that these cells give rise to hepatocytes and hepatic stellate cells. At early stages of mouse liver development, stellate cells with desmin-positive filaments were scattered in the liver parenchyma. However, the stellate cells definitely differed from hepatoblasts and hepatocytes in terms of their morphology and expression of desmin and hepatoblast and hepatocyte-specific E-cadherin in the liver. Fetal hepatoblasts and hepatocytes did not react with antidesmin antibodies, nor did desmin-positive stellate cells express E-cadherin in vivo and in vitro. Thus it is likely that desmin-positive stellate cells and hepatoblasts belong to different cell lineages. In the fetal liver, the desmin-positive stellate cells surrounded blood vessels, and extended their processes to haematopoietic cells and megakaryocytes. Many, but not all, hepatoblasts and hepatocytes were observed to be associated with the stellate cells. At fetal stages, cellular processes positive for desmin in the stellate cells were also thick compared with those in the adult liver, in which desmin-positive stellate cells lay in Disse's space and were closely associated with all hepatocytes. These developmental changes in the geography of desmin-positive cells in the liver parenchyma and their morphology may be associated with their maturation and interactions with other cell types

Videofluoroscopic and Manometric Evaluation of Swallowing Function in Patients with Multiple System Atrophy

We investigated swallowing function of 29 patients with multiple system atrophy (MSA) by videofluoroscopy and manometry. Abnormal findings in videofluoroscopy were generally consistent with those in Parkinson's disease. Although findings of videofluoroscopy were not correlated with a history of aspiration pneumonia, severity of disease was significantly correlated with a history of aspiration pneumonia. Oropharyngeal and hypopharyngeal swallowing pressures of the patients were decreased to 73.9 ± 48.4 mm Hg and 85.3 ± 42.9 mm Hg, respectively, both of which were significantly different from the pressures of the control group. Incomplete relaxation of the upper esophageal sphincter was seen in 23.1% of the MSA patients, all of whom had had MSA for more than 5 years. In conclusion, patients with MSA are at risk for aspiration pneumonia as disease severity increases, and the swallowing function of patients with more than 5 years' duration of MSA should be routinely followed up with both videofluoroscopy and manometry. </jats:p

Vocal fold motion impairment in patients with multiple system atrophy: evaluation of its relationship with swallowing function

Objective: To elucidate the relationship between VFMI and dysphagia in MSA. Methods: We evaluated swallowing function of 36 MSA patients with and without VFMI, by videofluoroscopy, and investigated the relationship between VFMI and pharyngeal swallowing function. Results: VFMI was found in 17 patients (47.2%). Patients with VFMI had advanced severity of the disease. Although there was a tendency for bolus stasis at the pyriform sinus and the upper oesophageal sphincter opening to be more involved in patients with VFMI, statistical analysis did not show significant differences in swallowing function of MSA patients between with and without VFMI. In contrast, patients who underwent a tracheotomy ultimately required tube feeding or a laryngectomy. Conclusions: Appearance of VFMI is a sign of disease progression but does not necessary mean patients should change their way of taking nutrition. However, MSA patients who need a tracheotomy might have advanced to a high-risk group for dysphagia. Appropriate evaluation and treatment for VFMI and dysphagia are required to maintain patients' quality of life in MSA