高分子修飾微粒子と液晶からなる物理ゲルの基礎物性と応用に関する研究

筑波大学 (University of Tsukuba)201

Helmholtz: A Verifier for Tezos Smart Contracts Based on Refinement Types

27th International Conference, TACAS 2021, Held as Part of the European Joint Conferences on Theory and Practice of Software, ETAPS 2021, Luxembourg City, Luxembourg, March 27 - April 1, 2021Part of the Lecture Notes in Computer Science book series (LNTCS, volume 12652)A smart contract is a program executed on a blockchain, based on which many cryptocurrencies are implemented, and is being used for automating transactions. Due to the large amount of money that smart contracts deal with, there is a surging demand for a method that can statically and formally verify them. This tool paper describes our type-based static verification tool HELMHOLTZ for Michelson, which is a statically typed stack-based language for writing smart contracts that are executed on the blockchain platform Tezos. HELMHOLTZ is designed on top of our extension of Michelson’s type system with refinement types. HELMHOLTZ takes a Michelson program annotated with a user-defined specification written in the form of a refinement type as input; it then typechecks the program against the specification based on the refinement type system, discharging the generated verification conditions with the SMT solver Z3. We briefly introduce our refinement type system for the core calculus Mini-Michelson of Michelson, which incorporates the characteristic features such as compound datatypes (e.g., lists and pairs), higher-order functions, and invocation of another contract. HELMHOLTZ successfully verifies several practical Michelson programs, including one that transfers money to an account and that checks a digital signature

Helmholtz: A Verifier for Tezos Smart Contracts Based on Refinement Types

A smart contract is a program executed on a blockchain, based on which many cryptocurrencies are implemented, and is being used for automating transactions. Due to the large amount of money that smart contracts deal with, there is a surging demand for a method that can statically and formally verify them. This article describes our type-based static verification tool HELMHOLTZ for Michelson, which is a statically typed stack-based language for writing smart contracts that are executed on the blockchain platform Tezos. HELMHOLTZ is designed on top of our extension of Michelson’s type system with refinement types. HELMHOLTZ takes a Michelson program annotated with a user-defined specification written in the form of a refinement type as input; it then typechecks the program against the specification based on the refinement type system, discharging the generated verification conditions with the SMT solver Z3. We briefly introduce our refinement type system for the core calculus Mini-Michelson of Michelson, which incorporates the characteristic features such as compound datatypes (e.g., lists and pairs), higher-order functions, and invocation of another contract. HELMHOLTZ successfully verifies several practical Michelson programs, including one that transfers money to an account and that checks a digital signature

POEMS Syndrome in a 20-year-old Patient Diagnosed Following a Complaint of Reduced Visual Acuity

We report a case of POEMS syndrome in a 20-year-old patient diagnosed after visiting an eye clinic with a chief complaint of reduced visual acuity. A male university student aged 20 years was referred to our department complaining of blurred vision in both eyes that had persisted for 1 month. He also noted headache, nausea, and paresthesia in the lower extremities around the same time. The visual acuity of his right and left eye was 20/40 and 20/20, respectively. Optic disc edema and serous retinal detachment were present. Brain magnetic resonance imaging showed no intracranial abnormalities, while elevated cerebrospinal fluid pressure, reduced nerve conduction velocity in both lower extremities, hepatosplenomegaly, M proteinemia, high blood VEGF levels, osteoblastic and osteolytic changes in the spine, and atypical plasma cells in bone lesions were noted. From the above findings, the patient was diagnosed with POEMS syndrome. He received high-dose dexamethasone, thalidomide, and radiotherapy on the sacral mass, followed by high-dose melphalan with autologous stem-cell support, and showed subsequent systemic and ophthalmologic improvement. Here, we report the youngest case ever of POEMS syndrome with ocular manifestation. If patients have optic disc edema in both eyes with no intracranial space-occupying lesion, POEMS syndrome should be considered in differential diagnosis, regardless of age

Green fluorescent cAMP indicator of high speed and specificity suitable for neuronal live-cell imaging

Cyclic adenosine monophosphate (cAMP) is a canonical intracellular messenger playing diverse roles in cell functions. In neurons, cAMP promotes axonal growth during early development, and mediates sensory transduction and synaptic plasticity after maturation. The molecular cascades of cAMP are well documented, but its spatiotemporal profiles associated with neuronal functions remain hidden. Hence, we developed a genetically encoded cAMP indicator based on a bacterial cAMP-binding protein. This indicator “gCarvi” monitors [cAMP]i at 0.2 to 20 µM with a subsecond time resolution and a high specificity over cyclic guanosine monophosphate (cGMP). gCarvi can be converted to a ratiometric probe for [cAMP]i quantification and its expression can be specifically targeted to various subcellular compartments. Monomeric gCarvi also enables simultaneous multisignal monitoring in combination with other indicators. As a proof of concept, simultaneous cAMP/Ca2+ imaging in hippocampal neurons revealed a tight linkage of cAMP to Ca2+ signals. In cerebellar presynaptic boutons, forskolin induced nonuniform cAMP elevations among boutons, which positively correlated with subsequent increases in the size of the recycling pool of synaptic vesicles assayed using FM dye. Thus, the cAMP domain in presynaptic boutons is an important determinant of the synaptic strength

Can poor treatment of workers be legitimated when they have passion for work?: Reexamining findings of Kim et al. (2020)

In Japan, overwork has often been reported and criticized by the media as well as the public. Jobs are, however, often regarded as giving workers a sense of fulfilment and enjoyment, leading to their willingness to work extra hours. Based on the findings of Kim et al. (2020), we conducted two studies to investigate whether poor treatment of a worker can be legitimated when he/she is passionate about his/her work. In line with previous research, we found that a passionate worker was perceived to be volunteering to do extra jobs without compensation if given the chance and to regard the work as a reward in and of itself. However, unlike Kim et al., we did not find any mediating effects of these two perceptions on legitimating poor treatment of passionate workers. The reason why we failed to replicate the findings of Kim et al. are discussed in terms of Japanese people’s awareness of the hardship and unfairness of overwork.本論文は，2020年度に広島大学教育学部で開講された心理学実験において，第1著者の指導により第2著者から第5著者が実施した研究をもとに執筆したものである。また，本研究はJSPS科研費JP18K03007の助成を受けた

An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3

α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson’s disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. In order to characterize the molecular mechanisms that underlie the interactions between FABP3 and αSyn that modulate the cellular accumulation of the latter, in this report, we used in vitro fluorescence assays combined with fluorescence microscopy, transmission electron microscopy, and quartz crystal microbalance assays to characterize in detail the process and consequences of FABP3-αSyn interaction. We demonstrated that binding of FABP3 to αSyn results in changes in the aggregation mechanism of the latter; specifically, a suppression of fibrillar forms of αSyn, and also the production of aggregates with an enhanced cytotoxicity toward mice neuro2A cells. Since this interaction involved the C-terminal sequence region of αSyn, we tested a peptide derived from this region of αSyn (αSynP130-140) as a decoy to prevent the FABP3-αSyn interaction. We observed that the peptide competitively inhibited binding of αSyn to FABP3 in vitro and in cultured cells. We propose that administration of αSynP130-140 might be used to prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby preventing the progression of Parkinson’s disease

The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

SummaryEndocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β (DGLβ). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLα knockout mice, whereas the retrograde suppression was intact in DGLβ knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLα knockout brains, whereas the 2-AG content was normal in DGLβ knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLα, but not by DGLβ, mediates retrograde suppression at central synapses

Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3

Runx2 and Sp7 are essential transcription factors for osteoblast differentiation. However, the molecular mechanisms responsible for the proliferation of osteoblast progenitors remain unclear. The early onset of Runx2 expression caused limb defects through the Fgfr1?3 regulation by Runx2. To investigate the physiological role of Runx2 in the regulation of Fgfr1?3, we compared osteoblast progenitors in Sp7?/? and Runx2?/? mice. Osteoblast progenitors accumulated and actively proliferated in calvariae and mandibles of Sp7?/? but not of Runx2?/? mice, and the number of osteoblast progenitors and their proliferation were dependent on the gene dosage of Runx2 in Sp7?/? background. The expression of Fgfr2 and Fgfr3, which were responsible for the proliferation of osteoblast progenitors, was severely reduced in Runx2?/? but not in Sp7?/? calvariae. Runx2 directly regulated Fgfr2 and Fgfr3, increased the proliferation of osteoblast progenitors, and augmented the FGF2-induced proliferation. The proliferation of Sp7?/? osteoblast progenitors was enhanced and strongly augmented by FGF2, and Runx2 knockdown reduced the FGF2-induced proliferation. Fgfr inhibitor AZD4547 abrogated all of the enhanced proliferation. These results indicate that Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation, at least partly, by regulating Fgfr2 and Fgfr3 expression

Science Teaching to Develop Pupils' Scientific Viewpoints and Ways of Thinking : The Possibility for Instructing the 'Energy Conversion' in Elementary School Science

小学校中学年B区分の学習内容を相互に関連付けて考えるための視点として「エネルギー変換」を取り上げ、これをキーワードにした教材開発と授業設計を行った。岡山大学教育学部附属小学校の第4学年の児童を対象に研究授業を行い、児童の変容を学習の記録や授業前後のコンセプトマップの記述をもとに分析した。その結果、児童の中には、既習事項である「光」「熱」「電気」「力」とそれらがもたらす現象とを、相互に関連付けて考えようとする反応が見られるようになった。Attempts were made to correlate learning contents with each other in the physical science of elementary school science. The authors approached this subject from the energetic viewpoint. We developed some materials and disigned an instructon, based on the 'energy conversion.' One author conducted a science class to the fourth graders of elementary school attached to Okayama University. Then we made an analysis of the children's records of learning in class, and used a concept mapping. In this survey, it was found that some of the pupils tried to associate 'light', 'heat', 'electricity', and 'force' with some phenomena that were brought about from these concepts