Answer Refinement Modification: Refinement Type System for Algebraic Effects and Handlers

Algebraic effects and handlers are a mechanism to structure programs with computational effects in a modular way. They are recently gaining popularity and being adopted in practical languages, such as OCaml. Meanwhile, there has been substantial progress in program verification via refinement type systems. However, thus far, there has not been a satisfactory refinement type system for algebraic effects and handlers. In this paper, we fill the void by proposing a novel refinement type system for algebraic effects and handlers. The expressivity and usefulness of algebraic effects and handlers come from their ability to manipulate delimited continuations, but delimited continuations also complicate programs' control flow and make their verification harder. To address the complexity, we introduce a novel concept that we call answer refinement modification (ARM for short), which allows the refinement type system to precisely track what effects occur and in what order when a program is executed, and reflect the information as modifications to the refinements in the types of delimited continuations. We formalize our type system that supports ARM (as well as answer type modification) and prove its soundness. Additionally, as a proof of concept, we have implemented a corresponding type checking and inference algorithm for a subset of OCaml 5, and evaluated it on a number of benchmark programs. The evaluation demonstrates that ARM is conceptually simple and practically useful. Finally, a natural alternative to directly reasoning about a program with delimited continuations is to apply a continuation passing style (CPS) transformation that transforms the program to a pure program. We investigate this alternative, and show that the approach is indeed possible by proposing a novel CPS transformation for algebraic effects and handlers that enjoys bidirectional (refinement-)type-preservation.Comment: 66 page

Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer.</p> <p>Methods</p> <p>PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status.</p> <p>Results</p> <p>PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (<it>P </it>= 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression.</p> <p>Conclusions</p> <p>We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.</p

A 90-day Feeding Toxicity Study of l-Serine in Male and Female Fischer 344 Rats

A subchronic feeding study of l-serine (l-Ser) was conducted with groups of 10 male and 10 female Fischer 344 rats fed a powder diet containing 0, 0.06, 0.5, 1.5 or 5.0% concentrations of l-Ser for 90 days. There were no toxicologically significant, treatment-related changes with regards to body weight, food intake, water intake or urinalysis data. In several of the hematology, serum biochemistry and organ weight parameters, significant changes were observed between some of the treated groups and the controls. All these changes, however, were subtle and lacked any corresponding pathological findings. In addition, the increased or decreased values remained within the range of the historical control values. In fact, histopathological assessment revealed only sporadic and/or spontaneous lesions. In conclusion, the no-observed-adverse-effect-level (NOAEL) for l-Ser was, therefore, determined to be at least a dietary dose of 5.0% (2765.0 mg/kg body weight/day for males and 2905.1 mg/kg body weight/day for females) under the present experimental conditions

In-situ Simple Investigations on Long-Term Recovery Tendency of Liquefied ground

departmental bulletin pape

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)

Introduction: In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC. Methods and analysis: This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoint are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias. Ethics and dissemination: This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals

授業支援システムを用いたプログラミング基礎教育の授業実践

大学のプログラミング基礎教育において修得させたい能力は、初歩的なプログラミング能力、課題内容に関して相談できるコミュニケーション能力、論理的思考能力、自己学習能力などである。これらの能力を持つ学習者が世間一般や産業界から求められていると考える。しかし、現状では、積極的に自分でプログラムを考えている学習者は少なく、プログラムの作成から実行までの操作ができれば満足している学習者が多く見受けられる。また、プログラミング初心者は、授業内容が進むにつれて、プログラムの構造が複雑になるため、途中で構造を作ることができなくなり、論理的思考を身につけるまでに至らないことが多い。教員が学習者の学習内容の理解度を把握し、理解度が低い内容は次回の授業に反映させて、つまづきをなくして次の内容に進む工夫が必要と考える。授業を受ける学習者は、高校の教科「情報」で教育をうけており、最低限の機器操作能力は持っているが、抽象的な数操作や概念理解の学習経験が少ないうえ、積極的に学習する心構えは希薄であり、授業活動を支援するシステムが必要となる。そこで、これまでの授業実践より、授業設計に役立つ知見を収集し、それらを組み合わせた授業支援システムを開発した。本稿では、2007年度に実施した授業支援システムを用いた授業実践について述べる