Von Neumann redux: revisiting the self-referential logic of machine reproduction using the Avida world

We introduce the distinctive, self-referential, logic of self-reproduction originally formulated by John von Neumann and present some initial results from a novel implementation of this abstract architecture, embedded within the Avida world. These show that, with this particular implementation, in this particular world, the von Neumann architecture proves to be evolutionarily unstable and degenerates, surprisingly easily, to a primitive, non-self-referential, “copying” or “template replication”, mode of reproduction. We briefly discuss some implications, and sketch prospects for further investigation

Analysing the mutational pathways of a von Neumann self-reproducer within the Avida world

The architecture of machine self-reproduction proposed by John von Neumann is studied within an artificial life platform known as Avida. To shed light on the evolutionary potential of the von Neumann style self-reproduction within the Avida world, we preliminarily characterise a hand-designed self-reproducer by extensive single-point mutation analysis. Although not surprisingly, the vast majority of the single-point mutants were classified as infertile, whereas the rest minorities as fertile and as yet unclassified. We conclude this paper by suggesting the possible enhancement of the analysis

On the evolution of genotype-phenotype mapping: exploring viability in the Avida articial life system

The seminal architecture of machine self-reproduction originally formulated by John von Neumann underpins the mechanism of self-reproduction equipped with genotype and phenotype. In this thesis, initially, a hand-designed prototype von Neumann style selfreproducer as an ancestor is described within the context of the artificial life system Avida. The behaviour of the prototype self-reproducer is studied in search of evolvable genotype-phenotype mapping that may potentially give rise to evolvable complexity. A finding of immediate degeneration of the prototype into a self-copying mode of reproduction requires further systematic analysis of mutational pathways. Through demarcating a feasible and plausible characterisation and classification of strains, the notion of viability is revisited, which ends up being defined as quantitative potential for exponential population growth. Based on this, a framework of analysis of mutants' evolutionary potential is proposed, and, subsequently, the implementation of an enhanced version of the standard Avida analysis tool for viability analysis as well as the application of it to the prototype self-reproducer strain are demonstrated. Initial results from a one-step single-point-mutation space of the prototype, and further, from a multi-step mutation space, are presented. In the particular case of the analysis of the prototype, the majority of mutants unsurprisingly turn out to be simply infertile, without viability; whereas mutants that prove to be viable are a minority. Nevertheless, by and large, it is pointed out that distinguishing reproduction modes algorithmically is still an open question, much less finer-grained distinction of von Neumann style self-reproducers. Including this issue, speciifc limitations of the enhanced analysis are discussed for future investigation in this direction

Evaluation of Pharyngeal Airway in Acromegaly

Objectives: Perioperative airway management may be particularly challenging in patients with acromegaly undergoing trans‐sphenoidal pituitary surgery (TSS). Management for airway obstruction is required prior to pituitary surgery to minimize perioperative hypoxia. The purpose of this retrospective study was to evaluate airway obstruction by simulation of computational fluid dynamics (CFD) using computed tomography (CT) images in patients who had undergone TSS. Methods: CT images of the nasopharyngeal airways of patients with acromegaly (n = 5) or nonfunctional pituitary adenoma (n = 6) undergoing TSS from April 2012 to January 2017 were used to construct these airways in three dimensions. Estimated airflow pressure and velocity in the retropalatal airway (RA), oropharyngeal airway (OA), and hypopharyngeal airway (HA) were simulated using CFD. Results: Estimated pharyngeal airflow pressure in the HA, OA, and RA was significantly greater in patients with acromegaly than in those with nonfunctional pituitary adenomas whereas the estimated pharyngeal airflow velocity was significantly impaired only in the RA of patients with acromegaly. Minimum postoperative SpO2 both within 3 hours and from 3 to 12 hours after the end of anesthesia was significantly lower in the patients with acromegaly. Additionally, estimated volume of tongue and pharyngeal airflow pressure in the HA, OA, and RA correlated with minimum postoperative SpO2. Conclusion: Pharyngeal airflow pressure estimated from CT images is high in patients with acromegaly, and these values correlate with postoperative minimum values for SpO2. Preoperative evaluation of CT images by CFD can predict difficulty in airway management and perioperative hypoxia

Aging and Diversity of Medical Needs: Cost of illness of cerebrovascular disease in each prefecture of Japan

Background: Aging in Japan is advancing most rapidly in the world, and is expected to increase demand of medical services more in near future. Aging is uneven and progress of the aging varies from regions resulting in great differences in medical needs. In order to supply the needs for medical services, Japanese government developed “Regional Medical Vision”, which estimates the near future requirements for medical resources. However, this is a plan for redistribution of medical resources taking into only future changes of population composition based on current situation. In fact, each region has diversity of medical needs, and it is difficult to use average medical needs even if they are adjusted by population structures. In consideration of such situation, we tried to estimate the social burden of major diseases of each region in order to estimate the medical needs. We picked up cerebrovascular diseases (CVD, ICD10 code: I60 - I69) and dementia (ICD10code: F01, F03, G30), and calculated their social burden of all 47 prefectures in Japan that have great authority for health policy. Method: Modifying the COI method developed by Rice D, we newly defined and estimated C-COI of CVD (ICD10 code: I60 - I69) and dementia (ICD10code: F01, F03, G30). C-COI consists of five parts; direct cost (medical), morbidity cost, mortality cost, direct cost (long term care (LTC)) and informal care cost (family’s burden). Direct cost (medical) is medical cost of each disease. Morbidity cost is opportunity cost for inpatient care and outpatient care. Mortality cost is measured as the loss of human capital (human capital method). These three costs are known as components of original cost of illness by Rice D. Direct cost (LTC) is long term care insurance benefits. Family’s burden is “unpaid care cost” by family, relatives and friends in-home and in-community (opportunity cost). We calculated such costs at 2013/2014 using Japanese official statistics. Results: The total C-COI of CVD in Japan was about 6,177 billion JPY, the maximum was 621 billion JPY in Tokyo and the minimum was 33 billion JPY in Tottori (Tokyo/Tottori=18.8), whereas the total C-COI of dementia was 3,778 billion JPY, the maximum was 341 billion JPY in Tokyo and the minimum was 22 billion JPY in Tottori (Tokyo/Tottori=15.5). The C-COI per capita of CVD in Japan was about 48 thousand JPY, the maximum was 66 thousand JPY in Kagoshima and the minimum was 38 billion JPY in Saitama (Kagoshima/Saitama=1.7), whereas the total C-COI of dementia was 3,778 billion JPY, the maximum was 46 thousand JPY in Shimane and the minimum was 22 thousand JPY in Chiba (Shimane/Chiba=2.1). Conclusion: We substantiated a method to calculate the social burden of medical care and LTC care for each prefecture using C-COI methods. In both diseases, a large difference was found in total costs per capita and components ratio between prefectures. The situations of social burden of diseases has diversity among prefectures. When estimating the future medical needs of each region, it is necessary to take each regional condition into account

FFC Ceramic Water(TM) Enhances Plant Apyrase Activity

The FFC ceramics(TM) from FFC Japan Co., Ltd. are now widely used in the fields of agriculture, fishery and food industry in Japan. Recently the FFC ceramic beads-based technology has been also applied to meet several environmental problems including pollution in sea, lakes and rivers. In this study the FFC ceramic water was tested for effect on plant enzyme, potato apyrase (EC 3.6.1.5; ATP-diphosphohydrolase), which hydrolyses nucleoside triphosphate (NTP) and -diphosphate (NDP) to produce corresponding nucleoside monophosphate (NMP) and inorganic phosphate (Pi). Addition of the FFC ceramic water to the enzyme reaction mixture markedly enhanced ATP-hydrolyzing activity, when used as ATP as substrate. However, the concomitant presence of Ca(2+) chelator, EGTA (O,O'-bis(2-aminoethyl)ethyleneglycol-N,N,N',N'-tetraacetic acid) with the FFC ceramic water, completely abolished the enzyme activation. In fact, exogenous calcium ion such as CaSO4 mimicked the FFC ceramic water. These results indicate that apyrase activation by the FFC ceramic water largely depends on calcium ions. On the other hand, when the FFC ceramic water prepared from "used" ceramics was tested for the apyrase activity, the enhanced effect on apyrase was decreased compared to the FFC ceramic water from "new" ones. This result, consistent with our present data covering concentration of calcium ions and conductivity, indicates that long and/or successive usage of the ceramic beads results in decrease of contents of released minerals, especially calcium ions. The apyrase-based enzyme assay presented here is probably applicable to estimate and quantify the effect of FFC ceramic water.本報は，FFC セラミックス(TM)（㈱エフエフシー・ジャパン）で調製した FFC セラミック水（FFC 水）の植物アピラーゼ（EC 3.6.1.5）の活性に及ぼす直接的な作用について調べたものである．FFC 水はアピラーゼがもつ ATP加水分解活性を促進し，その作用は反応液への添加量に依存した．先の無機元素分析結果から，FFC 水に含まれる主要な塩類はCa(2＋)であることが判明している．そこで，Ca(2＋)キレート剤EGTAを反応液へ加え，その影響について調べたところ，FFC 水による活性化作用は消失することが明らかとなった．また，FFC 水と類似の作用は，硫酸カルシウム，塩化カルシウムまたは硝酸カルシウムの添加で認められ，陰イオンの種類によって明確な違いはなかった．これらの結果から，FFC 水が植物アピラーゼに及ぼす活性化作用の一因は，セラミックスから遊離する Ca(2＋)に依存しているものと推察された．一方，アピラーゼ活性を指標として，使用済のセラミックスから調製した FFC 水の効果について検討したところ，未使用からの水と比べて，カルシウム濃度ならびに活性化作用の顕著な低下が認められた．このことは，継続的な使用によってセラミックスから遊離する塩類，特にカルシウムの溶出量が大きく変わることを意味し，アピラーゼを用いた本検定が，FFC 水の効果を定量的に確かめる方法の一つとして利用できると考えられた．以上，これらの結果を総合して，FFC水の植物酵素への直接的作用，ならびに植物への施用によって効果が現れる耐病性獲得作用との関連について考察した

Exploring the effect of an augmented reality literacy programme for reading and spelling difficulties for children diagnosed with ADHD

AbstractChildren diagnosed with attention deficit hyperactivity disorder (ADHD) experience a variety of difficulties related to three primary symptoms: hyperactivity, inattention and impulsivity. The most common type of ADHD has a combination of all three symptom areas. These core symptoms may negatively impact the academic and social performance of children throughout their school life. The AHA (ADHD-Augmented) project focused specifically on the impact of digital technologies' intervention on literacy skills of children that participated in the pilot study and were diagnosed with ADHD prior to the intervention. Existing research has shown that augmented reality (AR) can improve academic outcomes by stimulating pupils' attention. AHA project aimed at implementing an evidence-based intervention to improve ADHD children's reading and spelling abilities through the enhancement of an existing literacy programme with AR functionality. The present paper reports preliminary findings of the pilot study aimed at evaluating the effectiveness of the AHA system in promoting the acquisition of literacy skills in a sample of children diagnosed with ADHD compared to the literacy programme as usual. Background information on the main characteristics and difficulties related to the teaching and learning process associated with children diagnosed with ADHD are first introduced; the design and methodology of the AHA project intervention are also described. The preliminary findings have shown that AHA project succeeded in delivering an AR solution within an existing online literacy programme, which integrates a set of specific technologies and supports interactive educational content, services, assessment, and feedback

土壌改質材 FFC エースによるオオムギの生育と収量の促進効果

The effects of a unique soil conditioner, FFC-ace, on photosynthesis, transpiration, growth and yield of barley were examined in a field experiment. FFC-ace well-mixed with sandy soil greatly enhanced root and shoot growth, tillering and the number of grains per stock. The total yield in the treated plot increased by about 172%. The plants grown in the FFC-ace plot were greener and contained a higher level of chlorophyll, compared with the control. Photosynthesis and transpiration, which are tightly linked to productivity were also significantly enhanced at the broad range of photon flux observed in our study. The quality of grain harvested from the FFC-ace plot was similar to the control plot in terms of nutritional and inorganic components. The increased photosynthesis in the FFC-ace treated barley reflects a higher absorption of CO(2) from the atmosphere. It was also noted that the efficiency of water utilization for photosynthesis was significantly greater under the high light intensity in the treated plot. The relationship between application of FFC-ace and absorption of atmospheric CO(2) is discussed. Our investigation provides data showing that application of FFC-ace to soil significantly reduces water requirements for plant growth and yield.本報は，㈱エフエフシー・ジャパンから販売されている土壌改質材FFCエースTMの作物の生長促進効果について，2006年11月から翌年６月，本学農学部内の実験圃場で実施された，オオムギの生育ならびに収量調査に関する試験結果をとりまとめたものである．実施圃場の砂土壌にFFCエースを所定量混和した区画を設け，オオムギの種子を播種した．なお，対照区は非導入土壌とした．定期的に行った生育調査の結果，FFCエースを導入した土壌では非導入の区画と比べて，生育初期における根の生育が良好となり，地上部における分けつ数の増加とともに穂の生長も旺盛となって，１穂当たりの収穫量（粒数）の著しい増加をもたらした．結果，FFCエース導入区における全収量は非導入区と比べて約1.7倍となった．また，それぞれから収穫したオオムギ粒に含まれる栄養価ならびに無機元素類の量には，FFCエースの導入，非導入によって大きな違いは認められず，導入の効果は収量に大きく反映された．事実，調査期間中に行った測定から，FFCエースを投入した土壌で生育するオオムギ葉は高いクロロフィル量を示しており，光合成が促進されているものと考えられた．実際，播種後４ヶ月目以降，光合成ならびに蒸散速度値を測定した結果，FFCエース導入区で生育したオオムギでは常に高い値を示した．また，FFCエースの導入によって強光条件下における水利用効率が促進された．本報告では，FFCエースの投与と空気中からの二酸化炭素の吸収量との関連について考察するとともに，併せて，FFCエースの土壌への導入によって作物の生育に必要な灌水量を大きく減らすことができる可能性についても言及したい

[18F]fluoro-2-deoxyglucose-positron emission tomography を用いた進行口腔扁平上皮癌における術前化学放射線療法による治療効果判定の検討

BACKGROUND: [18F]fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) is widely used to evaluate tumor metabolic activity. The aim of this study was to evaluate the usefulness of FDG-PET in assessing the histopathological response to preoperative concurrent chemoradiotherapy (CRT) in patients with oral squamous cell carcinoma (OSCC). METHODS: Forty-five patients with resectable advanced OSCC who had received preoperative CRT followed by tumor ablative surgery between January 2004 and December 2011 were included in the study. All patients underwent FDG-PET before and after preoperative CRT. The maximum standardized uptake value (SUVmax) before (pre-SUV) and after preoperative CRT (post-SUV) and the SUVmax reduction rate (ΔSUV %) were used to evaluate the response to preoperative CRT. Correlations among SUVmax, histopathological response, and expression of cancer antigen Ki-67 and hypoxia-inducible factor-1α (HIF-1α) were analyzed. RESULTS: Preoperative CRT significantly reduced intratumoral FDG uptake (P < 0.001). The pre-SUV and post-SUV were significantly lower in patients with a pathological complete response (pCR) than in those with a non-pCR (pre-SUV P = 0.037; post-SUV P = 0.001). ΔSUV % was higher in patients with pCR than in those with non-pCR (P = 0.029). The pre-SUV was significantly correlated with Ki-67 and HIF-1α expression in pretreatment biopsy specimens (Ki-67 P = 0.046, R = 0.292; HIF-1α P = 0.007, R = 0.385). The expression of both Ki-67 and HIF-1α was significantly lower in patients with pCR than in those with non-pCR (Ki-67 P < 0.001; HIF-1α P < 0.001). CONCLUSIONS: Low pre-SUV and post-SUV and high ΔSUV % may predict a good histopathological response to preoperative CRT. Ki-67 and HIF-1α expression in pretreatment biopsy specimens were predictors of histopathological response to preoperative CRT.博士（医学）・乙第1357号・平成27年3月16日© Springer International Publishing AG, Part of Springer Science+Business Media© Japan Society of Clinical Oncology 201