Deep learning has replaced conventional machine learning due to its superior performance when exposed to an enormous amount of data. Researchers in many disciplines are drawn to deep learning, including physics, medicine, humanities, etc. Since we expect that readers would like to apply this popular technique in their projects on laser technologies, this paper introduces the fundamentals of deep learning with some mathematics. We also provide the first step in coding a neural network in PyTorch Lightning over Python, which comes with -to- code on Google Colab, allowing novices to immediately get started.

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This paper investigates the intrinsic semantic meaning of kedo (‘but’) in utterance-final use and what kind of pragmatic effects an utterance appended with kedo would derive. I explain how softening or hedging effects are derived by the utterance-final use of kedo. I compare kedo in utterance-final use with that in utterance-medial use and point out the difference in its pragmatic function. I identify the pragmatic function of kedo within the framework of Relevance Theory which is a theory of communication and cognition.

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Studies on the pathogenesis of asthma attacks are limited, and the mechanism underlying asthma attacks remains obscure. This study aimed to clarify the characteristic cytokine profiles in asthma exacerbation. [Materials and Methods] Serum cytokine levels were measured in patients who visited the hospital for asthma attacks and compared with cytokine lev- els in patients with stable asthma and in normal par- ticipants. Serum interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17, IL-33, periostin, and thymic stromal lymph- opoietin (TSLP) concentrations were measured in 16 patients with asthma attacks, 49 patients with stable asthma, and 26 normal participants. [Results] IL-10, IL-13, and TSLP levels were signifi- cantly higher in patients with asthma attacks than in patients with stable asthma, whereas IL-5 and IL-17 levels were significantly lower. [Discussion] Asthma is a heterogeneous disease, and the pathology of an asthma attack will also vary from person to person. In some asthma endtypes, IL-13 production, which induces mucus secre- tion and bronchoconstriction, would contribute to develop asthma attacks. This IL-13 production is not prevented by the enhanced IL-10 production or step-up treatment (i.e., increased steroid inhalation etc.), although IL-10 can suppress IL-5 and IL-17 production.

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Coffee is a globally consumed beverage with potential health benefits. However, there are few reports about the effects of coffee on immunological functions. We previously reported that in an allergic mouse model, coffee intake prevented allergy development through augmentation of interleukin (IL)-12p40. In order to investigate the anti-allergic activity of coffee, we examined the effect of coffee on antigen (Ag)-specific responses of immune cells in vitro. Coffee treatment suppressed proliferation and IL-2 secretion of mouse splenocytes in the same way as splenocytes from mice administered coffee orally. However, IL-12p40 secretion decreased significantly as a result of in vitro coffee treatment, which was contrary to the results obtained from experiments of mice administered coffee orally. Therefore, modification associated with oral administration might influence the anti-allergic activity of coffee.

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Bisphenol A [2,2-bis(4-hydoxyphenyl)propane; BPA] is an endocrine disrupter widely used in polycarbonate plastics and epoxy resins. We investigated the effects of orally administered BPA on antigen-specific responses of the naïve immune system.
BPA was orally administered to T cell receptor transgenic mice, and the antigen-specific responses of immune cells were investigated. Administered BPA moderately reduced interleukin (IL)-2, 4, and interferon (IFN)-γ secretion and increases in IgA and IgG2a production.
Additionally, it was found that orally administered BPA increased antigen-specific IFN-γ production of T cells and modified whole antigen presenting cells (APCs) to suppress antigen-specific cytokine production from T cells.
These findings suggest that BPA can augment the Th1-type responses of naïve immune systems, though the bioavailability of orally administered BPA was low in our experiments.

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Streptococcus mutans glucan-binding protein C encoded by the gbpC gene is an important virulent factor in human dental caries. However, a nonsense mutation and several nucleotide substitutions in the gbpC gene have been detected in strain GS-5. Therefore, gbpC nucleotide sequences from 17 additional S. mutans strains were determined and single nucleotide polymorphisms were detected. Both conserved and polymorphic regions of the gbpC gene will be useful for estimation of functional domains of GbpC protein and identification of S. mutans strains.

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A 85-year-old woman with diabetes mellitus and prior myocardial infarction was transferred to the emergency room with loss of consciousness due to marked bradycardia caused by hyperkalemia. The T wave during right ventricular pacing was tall and tent-shaped while the concentration of serum potassium was high, and its amplitude during pacing was decreased after correction of the serum potassium level. Simultaneously with the correction, normal sinus rhythm was restored. The cause of hyperkalemia was considered to be several doses of loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), prescribed for her lumbago by an orthopedic specialist, in addition to the long-term intake of imidapril, an angiotensin-converting enzyme inhibitor (ACEI), prescribed for her hypertension by a cardiologist. This case warns physicians that the combination of NSAID and ACEI can produce serious side effects in aged patients who frequently suffer from hypertension, diabetes mellitus, ischemic heart disease, and degenerative joint disease. (Jpn Circ J 1999; 63: 1002 - 1003)

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The mdx mouse, a model of muscular dystrophy, lacks dystrophin, a cell membrane protein. It is known that this lack of dystrophin results in muscle fiber necrosis from 2 weeks after birth, and the majority of necrotic fibers are replaced by regenerated fibers by 4 weeks of age. Recent studies reported the detection of mitochondrial and endoplasmic reticulum stress proteins during muscle fiber necrosis in mdx mice, but did not histologically localize them to determine the timing of their expression during the process from cell necrosis to regeneration. Therefore, in this study, we investigated histological localization and gene-level expression in the mdx mouse masseter muscle of caspase-12 protein (among the caspases, which are cell stress-related genes) involved in the endoplasmic reticulum stress pathway. We observed caspase-12 expression in muscle cells that seemed to be in the process of necrosis in the mdx mouse masseter muscle at 2 weeks after birth, but not in regenerated muscle cells with centrally located nuclei observed at 3 to 4 weeks of age. These results suggest that due to the lack of dystrophin, it becomes difficult for muscle cells to maintain their morphology, and endoplasmic reticulum stress occurs to maintain cell morphology during the process of cell necrosis.

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Vibrio mimicus (V. mimicus) is a causative agent of human gastroenteritis and food poisoning. Although several toxic or virulence factors have been isolated from the bacterium, an enterotoxic hemolysin is a sole toxin produced by all clinical isolates. In the present study, we found that the antibody against the hemolysin significantly inhibited the fluid-accumulating action of the living cells inoculated into a rabbit ileal loop, and that the hemolysin gene (vmhA) was probably expressed by the bacterium in the ileal loop. Additionally, in spit of the comparable motility and similar proteome profiles, a vmhA mutant revealed the reduced fluid-accumulating activity. Theses findings suggest that the hemolysin contributes to full virulence of V. mimicus.

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Aquaporin-2 (AQP2) is one of the membrane water channel proteins expressed in principal cells of the kidney collecting ducts. In the basal state, AQP2 resides in the storage vesicles localized in the subapical cytoplasm. Upon stimulation with vasopressin, AQP2 is translocated to the apical plasma membrane by the exocytic fusion of the storage vesicles with the apical membrane. This translocation enables the transepithelial reabsorption of water from the lumen to the interstitium via AQP2 at the apical membrane and AQP3/AQP4 at the basolateral membrane. AQP2-storage vesicles are distinct from the endoplasmic reticulum, Golgi apparatus, trans-Golgi network, and lysosomes. The early endosomal marker EEA1 is colocalized with some of AQP2 vesicles. Further analyses in Madin-Darby canine kidney (MDCK) cells transfected with AQP2 revealed that subapical Rab11-positive/EEA1-negative smaller vesicles constitute part of the AQP2 storage vesicles for the translocation to the apical membrane. Termination of stimulation results in the retrieval of AQP2 to the larger EEA1-positive early endosomal compartment. AQP2 is then transferred to the subapical storage compartment in a PI3-kinase-dependent manner. GLUT4 is an isoform of glucose transporters whose localization is also regulated by vesicular trafficking induced by insulin stimulation. Comparison of the intracellular localization of AQP2 with GLUT4 suggests distinct regulation of AQP2 trafficking.

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  The key technical characteristics of the four main optical disc substrate materials are compared and glass is shown to have superior characteristics for this application. The various methods for formatting the different substrate materials are noted, and the alternate approaches to direct formatting glass reviewed. Recent developments in hot pressing which have the potential for the mass production of a low cost direct formatted glass substrate are described.

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To evaluate the involvement of lysophosphatidic acid receptor-1 (LPA1) gene alteration in pancreatic carcinogenesis, we investigated mutations in the LPA1 gene in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 30 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine and then L-methionine and a further administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/10, 10%) in the form of a GGA to GTA (Gly to Val) transversion at codon 355, and no mutations were detected in the three cell lines. These results suggest that the LPA1 gene mutation may play roles in a limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.

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Aquaporins (AQPs) are water channel proteins of cellular membranes serving in the permeation of water across the membrane. AQP families are found virtually in all types of life ranging from bacteria to plant and animal cells. In mammals, at least 13 isoforms of AQPs have been identified. They are classified into three subtypes: classical aquaporins, aquaglyceroporins, and superaquaporins. These AQPs are differentially expressed in a wide variety of cells and tissues in the body, and play important roles in water metabolism. In the kidney, at least 6 isoforms of AQPs, namely AQP1, AQP2, AQP3, AQP4, AQP6, and AQP7, are reported to be expressed. Water transfer occurs mainly in the proximal tubules and collecting ducts in the kidney. In the proximal tubules, AQP1 and AQP7 are expressed, among which AQP1 plays a major role in water reabsorption. In the collecting ducts, AQP2, AQP3, AQP4, and AQP6 are expressed. AQP3 and AQP4 are localized at the basolateral membrane. AQP2 is stored in the cytoplasmic vesicles and is translocated to the apical plasma membrane in response to antidiuretic hormone. Mutations of AQP2 lead to either loss of channel function or mistrafficking and result in nephrogenic diabetes insipidus, the inability to concentrate urine.

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道内109ヵ所の「道路画像情報」と「道路気象情報」をデータ放送で表示する「道カメラ」を公開しました。コンテンツの画像配信は「放送」ではなく「通信」側で行うため、テレビをネットワークに接続する必要がありますが、放送では送る事が難しい沢山の画像を使用できます。「道路画像情報」「道路気象情報」は、国土交通省北海道開発局が管理し、道路交通情報センターで販売されています。このデータを連続的に取得して加工し、公開サーバーへアップデートするシステムと、簡単に「道路画像情報」「道路気象情報」を閲覧できる、データ放送テンプレートを自社開発し、運用開始しましたので、ご紹介します。

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  免疫チェックポイント分子に対する阻害抗体の開発により，がん免疫療法の臨床応用が進んでいる．しかし，免疫チェックポイント阻害剤単剤で臨床効果が認められる患者は20-30％程度であるため，レスポンダーを識別するバイオマーカーの同定，およびノンレスポンダーで過剰もしくは不足している免疫応答を解明し，より効果的ながん免疫療法の開発が求められている．我々は抗腫瘍免疫応答の本態を明らかにするため，がん細胞の遺伝子変異に伴って生じる抗原（Neoがん抗原）とがん細胞内に存在する自己抗原由来で多くのがん患者で共通してみられる抗原（Sharedがん抗原）に対する免疫抑制機構について検討した．Sharedがん抗原特異的CD8+T細胞は，制御性T細胞により抑制され，不応答（抗原刺激に対してサイトカイン産生や細胞増殖をしない）状態に陥ることが明らかになった．一方でこれらの免疫抑制機構はNeoがん抗原特異的CD8+T細胞に対しては作動せず，十分な活性化が誘導された．以上より，Neoがん抗原が多くみられるがん患者では抗腫瘍免疫応答は

to の状態にあり，抗PD-1抗体などで局所の免疫抑制を解除することによって十分な臨床効果が認められるが，Sharedがん抗原が多い患者では，免疫抑制ネットワーク，とりわけ制御性T細胞を標的とするような新たながん免疫療法との併用の必要性が示唆された．

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