Bounded Verification of Higher-Order Stateful Programs

In this thesis we explore bounded verification techniques for higher-order stateful programs. We consider two settings: open and closed higher-order, which are defined by the type-order of free variables present in each. Closed higher-order programs allow free variables only if they are of ground type, whereas open higher-order programs generalise this by allowing free variables of arbitrary order. We elaborate on the challenges involved in reasoning within said settings, and define a higher-order stateful language—an ML-like -calculus with recursion and higher-order global state—as our vehicle of study. We define a Bounded Model Checking technique for closed higher-order programs via defunctionalization using nominal techniques, and a Symbolic Execution Game Semantics to perform Bounded Symbolic Execution of open higher-order programs. Contributions presented in this thesis involve theoretical and experimental results. On the theoretical side, all approaches defined herein are sound and bounded-complete in the sense that they report errors if and only if errors are reachable up to the given bound—all results necessary to show this are included. For the experimental side, we implemented prototype tools for each technique, collected and created benchmarks to test each higher-order setting, and measured the performance of our tools to compare them to other relevant existing tools. Results presented herein for closed and open higher-order programs have been published in SETTA 2019 and FSCD 2020 respectively

Literature review and analysis of the development of health outcomes assessment instruments in Chinese medicine

OBJECTIVE: To evaluate the development of health outcomes assessment instruments in Chinese medicine. METHODS: A comprehensive literature search for all published articles in China National Knowledge Infrastructure Database, Chongqing VIP Database and WANFANG Data was conducted. The studies that met the inclusion and exclusion criteria were used to extract information according to a predesigned assessment instrument. RESULTS: A total of 97 instruments for health outcome assessment in Chinese medicine were identified. Of these questionnaires, 7 were generic, 12 were condition-specific and 78 were disease-specific. All instruments were suitable for adults, children, and both men and women. These instruments aimed to evaluate the health-related quality of life, signs and symptoms as well as patient satisfaction and doctor-reported outcome. However, the descriptions were poorly constructed for some of the most basic parameters, such as the domains and items, administrative mode, response options, memory recall periods, burden evaluation, format, copyright, content validity, and other properties. CONCLUSION: The instrument development for health outcomes assessment in Chinese medicine is increasing rapidly; however, there are many limitations in current methodologies and standards, and further studies are needed. © 2013 Feng-bin Liu et al

Literature review and analysis of the application of health outcome assessment instruments in Chinese medicine

OBJECTIVE: To evaluate the application of health assessment instruments in Chinese medicine. METHODS: According to a pre-defined search strategy, a comprehensive literature search for all articles published in China National Knowledge Infrastructure databases was conducted. The resulting articles that met the defined inclusion and exclusion criteria were used for analysis. RESULTS: A total of 97 instruments for health outcome assessment in Chinese medicine have been used in fundamental and theoretical research, and 14 of these were also used in 29 clinical trials that were randomized controlled trials, or descriptive or cross-sectional studies. In 2 152 Chinese medicine-based studies that used instruments in their methodology, more than 150 questionnaires were identified. Among the identified questionnaires, 51 were used in more than 10 articles (0.5%). Most of these instruments were developed in Western countries and few studies (4%) used the instrument as the primary evidence for their conclusions. CONCLUSION: Usage of instruments for health outcome assessment in Chinese medicine is increasing rapidly; however, current limitations include selection rationale, result interpretation and standardization, which must be addressed accordingly

A Novel Approach to Molecular Recognition Surface of Magnetic Nanoparticles Based on Host–Guest Effect

A novel route has been developed to prepared β-cyclodextrin (β-CD) functionalized magnetic nanoparticles (MNPs). The MNPs were first modified with monotosyl-poly(ethylene glycol) (PEG) silane and then tosyl units were displaced by amino-β-CD through the nucleophilic substitution reaction. The monotosyl-PEG silane was synthesized by modifying a PEG diol to form the corresponding monotosyl-PEG, followed by a reaction with 3-isocyanatopropyltriethoxysilane (IPTS). The success of the synthesis of the monotosyl-PEG silane was confirmed with1H NMR and Fourier transform infrared (FTIR) spectroscopy. The analysis of FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed the immobilization of β-CD onto MNPs. Transmission electron microscopy (TEM) indicated that the β-CD functionalized MNPs were mostly present as individual nonclustered units in water. The number of β-CD molecules immobilized on each MNP was about 240 according to the thermogravimetric analysis (TGA) results. The as-prepared β-CD functionalized MNPs were used to detect dopamine with the assistance of a magnet

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer

<p>Abstract</p> <p>Background</p> <p>The phosphoinositide 3-kinase (PI3K)/Akt pathway plays a fundamental role in cell proliferation and survival in human tumorigenesis, including gastric cancer. <it>PIK3CA </it>mutations and amplification are two major causes of overactivation of this pathway in human cancers. However, until this work, there was no sound investigation on the association of <it>PIK3CA </it>mutations and amplification with clinical outcome in gastric cancer, particularly the latter.</p> <p>Methods</p> <p>Using direct sequencing and real-time quantitative PCR, we examined <it>PIK3CA </it>mutations and amplification, and their association with clinicopathological characteristics and clinical outcome of gastric cancer patients.</p> <p>Results</p> <p><it>PIK3CA </it>mutations and amplification were found in 8/113 (7.1%) and 88/131 (67%) gastric cancer patients, respectively. <it>PIK3CA </it>amplification was closely associated with increased phosphorylated Akt (p-Akt) level. No relationship was found between <it>PIK3CA </it>mutations and clinicopathological characteristics and clinical outcome in gastric cancer. <it>PIK3CA </it>amplification was significantly positively associated with cancer-related death. Importantly, Kaplan-Meier survival curves revealed that the patients with <it>PIK3CA </it>amplification had significantly shorter survival times than the patients without <it>PIK3CA </it>amplification.</p> <p>Conclusions</p> <p>Our data showed that <it>PIK3CA </it>mutations were not common, but its amplification was very common in gastric cancer and may be a major mechanism in activating the PI3K/Akt pathway in gastric cancer. Importantly, Kaplan-Meier survival curves revealed that <it>PIK3CA </it>amplification was significantly positively associated with poor survival of gastric cancer patients. Collectively, the PI3K/Akt signaling pathway may be an effective therapeutic target in gastric cancer.</p

Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line

<p>Abstract</p> <p>Background</p> <p>Key role of angiogenesis in tumor growth and metastasis based on accumulating evidence and recent progress of immunotherapy have led us to investigate vaccine therapy targeting tumor angiogenesis.</p> <p>Methods</p> <p>C57BL/6J mice were vaccinated with a syngeneic endothelial cell line Tpit/E by subcutaneous injection once a week. Prior to ninth vaccination, the mice were challenged with B16/F10 melanoma cells by subcutaneous inoculation on the back for the tumor growth model or by tail venous injection for the lung metastasis model. Development of subcutaneous tumor and lung metastasis was monitored by computed tomography scanning, which enabled accurate evaluation with the minimized sacrifice of mice.</p> <p>Results</p> <p>Vaccination with Tpit/E cells inhibited subcutaneous tumor growth and appearance of lung metastasis compared to control. Survival period was elongated in the Tpit/E vaccination in both of the two models. We also obtained hybridomas secreting specific antibodies to Tpit/E cells from a mouse vaccinated with the cells, indicating that specific immune response to the syngeneic endothelial cells was elicited.</p> <p>Conclusion</p> <p>These results suggest that vaccination with an autologous endothelial cell line may be effective against melanoma.</p

Schwann cell hamartoma: case report

<p>Abstract</p> <p>Background</p> <p>Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening.</p> <p>Case presentation</p> <p>We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract.</p> <p>Conclusion</p> <p>As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.</p

Genetic Variation in the EGFR Gene and the Risk of Glioma in a Chinese Han Population

Previous studies have shown that regulation of the epidermal growth factor gene (EGFR) pathway plays a role in glioma progression. Certain genotypes of the EGFR gene may be related to increased glioblastoma risk, indicating that germ line EGFR polymorphisms may have implications in carcinogenesis. To examine whether and how variants in the EGFR gene contribute to glioma susceptibility, we evaluated nine tagging single-nucleotide polymorphisms (tSNPs) of the EGFR gene in a case–control study from Xi'an city of China (301 cases, 302 controls). EGFR SNP associations analyses were performed using SPSS 16.0 statistical packages, PLINK software, Haploview software package (version 4.2) and SHEsis software platform. We identified two susceptibility tSNPs in the EGFR gene that were potentially associated with an increased risk of glioma (rs730437, p = 0.016; OR: 1.32; 95%CI: 1.05–1.66 and rs1468727, p = 0.008; OR: 1.31; 95%CI: 1.04–1.65). However, after a strict Bonferroni correction analysis was applied, the significance level of the association between EGFR tSNPs and risk of glioma was attenuated. We observed a protective effect of haplotype “AATT” of the EGFR gene, which was associated with a 29% reduction in the risk of developing glioma, while haplotype “CGTC” increased the risk of developing glioma by 36%. Our results, combined with previous studies, suggested an association between the EGFR gene and glioma development