Stability Analysis and Stabilization Strategies for Linear Supply Chains

Due to delays in the adaptation of production or delivery rates, supply chains can be dynamically unstable with respect to perturbations in the consumption rate, which is known as "bull-whip effect". Here, we study several conceivable production strategies to stabilize supply chains, which is expressed by different specifications of the management function controlling the production speed in dependence of the stock levels. In particular, we will investigate, whether the reaction to stock levels of other producers or suppliers has a stabilizing effect. We will also demonstrate that the anticipation of future stock levels can stabilize the supply system, given the forecast horizon is long enough. To show this, we derive linear stability conditions and carry out simulations for different control strategies. The results indicate that the linear stability analysis is a helpful tool for the judgement of the stabilization effect, although unexpected deviations can occur in the non-linear regime. There are also signs of phase transitions and chaotic behavior, but this remains to be investigated more thoroughly in the future.Comment: For related work see http://www.helbing.or

Effect of Oral Functional Training on Changes in Resting Saliva Secretion in Older Hemodialysis Patients

高齢血液透析患者の口腔乾燥には，日常的な水分摂取の制限と唾液腺自体の加齢性変化が関係していると考えられる．高齢血液透析患者の口腔乾燥改善には，まず十分な安静時唾液の分泌が必要と考え，それを促す手法の一つとして口腔機能訓練に着目した．本研究は，高齢血液透析患者に対して継続的な口腔機能訓練を行い，安静時唾液量の変化から訓練の効果を検証することを目的とした． 研究参加の同意が得られた軽度以上の口腔乾燥を有する高齢血液透析患者を，無作為に2群に分けた．歯科衛生士による口腔機能訓練（唾液腺マッサージ，舌運動訓練）を透析中（週3回）に12週間行った群を介入群，行わなかった群を対照群とした．研究開始前，2週後，4週後，8週後および12週後に，口腔内湿潤度と安静時唾液量を測定した．研究を完了した54名（介入群28名，対照群26名）について，群内および群間の比較には二元配置分散分析を，計測回ごとの多重比較にはBonfferoni法を用いて，統計解析を行った． 口腔機能訓練の実施による変化を検証した結果，口腔内湿潤度は，介入群の主効果および対照群との交互作用も有意であった（F（1,52）＝22.3，p＝0.03，F（4）＝3.5，p＝0.008）．群内の多重比較の結果，介入群は研究開始時と比較して，4週後以降で有意差が認められた（p＜0.05，p＜0.001，p＜0.05）が，対照群は有意差が認められなかった．安静時唾液は，介入群の主効果および対照群との交互作用も有意（F（1,52）＝18.6，p＜0.001，F（3）＝5.3，p＝0.002）であった．群内の多重比較の結果，介入群において，研究開始前と比較して4週後以降（p＜0.05，p＜0.001，p＜0.001）に有意な増加が認められた．一方，対照群において，2週後と12週後，4週後と12週後に有意な増加が認められた（p＜0.05，p＜0.05）．以上より，高齢血液透析患者に対する長期間（4週間以上）の唾液腺マッサージや舌運動訓練による口腔機能訓練は，安静時唾液分泌量を増加させる可能性が示唆された．Introduction:　Daily fluid restriction and aging-related atrophy of saliva glands might cause dry mouth in older hemodialysis patients. We hypothesized that greater saliva secretion is needed to relieve dry mouth and that this could be achieved by providing oral functional training to patients. The aim of this study was to investigate changes in resting saliva secretion after performing oral functional training for older hemodialysis patients with mild dry mouth. Materials and Methods:　Hemodialysis patients with mild dry mouth at Kawashima Hospital gave informed consent to participate in the study. They were then randomly divided into an intervention group (n＝31) and a control group (n＝30). The intervention group was provided oral functional training by a dental hygienist, including saliva gland massage for 30 s and tongue lateral movement for 12 weeks during dialysis treatment. The control group did not receive the training. Overall, 54 participants completed the experiment. Oral wetness was measured using a KISO-WeT Tester, and the amount of resting saliva secreted in 30 s was collected in a cotton roll and weighed. Measurements were implemented at baseline and at 2, 4, 8, and 12 weeks after starting the regimen. Results and Discussion:　In the intervention group, oral wetness at 4, 8, and 12 weeks was significantly higher than that at baseline (p＜0.05, p＜0.001, p＜0.05, respectively). No statistically significant differences were found in the control group. In the intervention group, the amounts of saliva secreted at 4, 8, and 12 weeks were significantly greater than that at baseline (p＜0.05, p＜0.001, p＜0.001, respectively). In the control group, the amount of saliva secreted at 12 weeks was significantly more than that at 2 and 4 weeks (p＜0.05, p＜0.05, respectively). Conclusion:　We concluded that performing oral functional training, which included salivary gland massage and tongue movement training for 4 or more weeks, could increase the amount of resting saliva secretion in older hemodialysis patients with mild dry mouth

Evaluation of alkylating pyrrole-imidazole polyamide conjugates by a novel method for high-throughput sequencer

N-Methylpyrrole-N-methylimidazole (PI) polyamides are a class of DNA minor groove binders with DNA sequence-specificity. DNA-alkylating PI polyamide conjugates are attractive candidates as anticancer drugs acting through DNA damage and its subsequent inhibition of cell proliferation. One example is a chlorambucil-PI polyamide conjugate targeting the runt-related transcription factor (RUNX) family. RUNX1 has pro-oncogenic properties in acute myeloid leukemia, and recently the chlorambucil-PI polyamide conjugate was demonstrated to have anticancer effects. Herein, we apply another DNA-alkylating agent, seco-CBI, to target the consensus sequence of the RUNX family. Two types of CBI conjugates were prepared and their binding properties were characterized by Bind-n-Seq analysis using a high-throughput sequencer. The sequencing data were analyzed by two methods, MERMADE and our new MR (motif identification with a reference sequence), and the resultant binding motif logos were as predicted from the pairing rules proposed by Dervan et al. This is the first report to employ the MR method on alkylating PI polyamide conjugates. Moreover, cytotoxicity of conjugates 3 and 4 against a human non-small cell lung cancer, A549, were examined to show promising IC[50]s of 120 nm and 63 nm, respectively. These findings suggest seco-CBI-PI polyamide conjugates are candidates for oncological therapy

Pharmacokinetic study of Paeoniflorin Paeonimetabolin-I and Glycyrrhetic acid in humans after oral administration of Paeony Root, Glycyrrhiza and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang)

The pharmacokinetics of Paeoniflorin (PF) , Paeonimetabolin-I (PM-I) and Glycyrrhetic acid (GA) after oral administration of the decoction of Paeony Root (PR) and Glycyrrhiza (GR) and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang ; SK) were studied using human subjects. Concerning the intra- and inter-individual variability of PF and PM-I after oral administration of SK, each inter-individual coefficient of variation (CV) of the pharmacokinetic parameters was larger than its intra-individual CV. There was no significant correlation between each pharmacokinetic parameter and each subject\u27s physiques. These results suggested that a large inter-individual variability were not caused by differences in the subjects\u27 physiques. Regarding a comparison of the pharmacokinetic parameters, AUC and Cmax of PF of PR were significantly higher than those of SK, and MRT and Tmax of PM-I of SK were significantly longer than those of PR. AUC of GA of SK was significantly higher than those of GR. There is the possibility that PR would be better than SK when a stronger efficacy of PR is expected in a short time, and SK would be beter than PR when a longer efficacy of PR or a stronger efficacy of GR is expected. ヒト健常人において芍薬・甘草・芍薬甘草湯経口投与時のペオニフロリン(PF),ペオニメタボリン-I(PM-I),グリチルレチン酸(GA)の葉物動態の研究を施行した。芍薬甘草湯投与後のPF,PMIの個体内・個体間変動については,各々の個体問変動係数が個体内変動係数よりも大きく,また,全ての薬物動態の各パラメータと被験者の体格との間には相関はみられなかった。芍薬・甘草と芍薬甘草湯との比較では,芍薬のPFのAUC,Cmaxが芍薬甘草湯のものに比較して有意に高値を示し,芍薬甘草湯のPM-IのMRT,Tmaxが芍薬に比較して有意に長かった。また,芍薬甘草湯のGAのAUCは甘革単独投与のものに比較して有意に高値を示した。このことから,短時間に芍薬のより強い効果を期待する際には芍薬単独で用い,芍薬成分のより長い効果や甘草成分のより強い効果を期待する際には芍薬甘草湯として投与する方がよい可能性がある

Association between Oral Health Conditions and Nutritional Status in Hemodialysis Patients

近年透析患者の高齢化が進んでおり，透析患者における低栄養と生命予後の関連が報告されている．低栄養の主な原因は食事摂取量の低下と考えられているが，これまでの研究で歯科的要因の関与については十分に検討されていない．本研究では，透析患者の栄養状態と現在歯数および咬合支持状態との関連を明らかにすることを目的として，透析医療機関に併設する歯科口腔外科を受診した透析歴1 年以上の血液透析患者155 名を対象に歯科初診時の口腔状態と直近の栄養指標を横断的に調査し，その関連性について統計学的に検討した．その結果，現在歯数および健全歯根膜表面積より算出される咬合支持能力指数（Normal Periodontal Ligament Index: NPLI）と標準化蛋白異化率（normalized protein catabolic rate: nPCR）の間に有意な正の相関を認めた（Spearman 順位相関係数検定，p<0.05）．また，Eichner分類で群分けした場合（A 群 vs B/C 群），nPCR は2 群間で有意な差を認めた（0.97±0.20 vs 0.90±0.17, スチューデントt 検定，p=0.023）．さらに，二項ロジスティック回帰分析の結果，nPCR が0.8 未満であることに現在歯数やEichner 分類B/C 群が関連することが示された（それぞれオッズ比（95% 信頼区間），p 値：0.945（0.907–0.985）， p=0.007，2.464（1.079–5.626），p=0.032）．nPCR はタンパク質摂取量を反映する指標であることから，血液透析患者において歯の喪失や不十分な咬合支持状態がタンパク質摂取不足に繋がる可能性が示唆された．本研究の結果から，血液透析患者の低栄養のリスクとして，歯数や咬合支持など口腔環境を考慮する必要があることが示唆された．Recently, concerns over malnutrition in hemodialysis patients have been highlighted, along with the aging of patients. The most important cause of malnutrition in hemodialysis patients is considered to be an inadequate dietary intake. However, the involvement of oral health conditions in the malnutrition of hemodialysis patients has not been fully elucidated. The aim of this study was to clarify the relationships between oral health conditions [number of remaining natural teeth and occlusion status] and nutritional status in hemodialysis patients. We evaluated and analyzed oral health conditions [number of remaining natural teeth and occlusion status] and the nutritional status of patients at their first visit to the Department of Oral Surgery in a hemodialysis hospital. 　We found significant correlations between the number of remaining teeth or occlusion status and normalized protein catabolic rate (nPCR). Significant differences between groups divided according to the Eichner index (Group A vs. Group B/C) were also found (0.97±0.20 vs. 0.90±0.17, respectively, Student’s t-test, p=0.023). Moreover, logistic regression analysis suggested that nPCR could be attributed to the number of remaining natural teeth and Eichner index (OR=0.945, 95% CI: 0.907-0.985; p=0.007 and OR=2.464, 95% CI: 1.079-5.626; p=0.032, respectively). Since nPCR is an indicator used for monitoring protein intake, tooth loss and an inadequate occlusion status might lead to decreased protein intake in hemodialysis patients. These results suggest that it is necessary to consider the number of remaining natural teeth and occlusion status as risks of malnutrition in hemodialysis patients

Direct quark transition potential for ΛN→NN\Lambda N \to NN decay

The weak $\Lambda N\to NN$ transition is studied in the valence quark model approach. The quark component of the two baryon system is described in the quark cluster model and the weak transition potential is calculated by evaluating the matrix elements of the $\Delta S=1$ effective weak Hamiltonian. The transition potential is applied to the decay of hypernuclei and the results are compared with available experimental data. The results indicate that direct quark process is significant and qualitatively different when compared with those in conventional meson-exchange calculations. The direct quark mechanism predicts the violation of the $\Delta I = 1/2$ rule for this transition.Comment: 36 pages, LaTeX, 2 figures (uuencoded Postscript) included using epsf.te

Weak Decay of Λ\Lambda in Nuclei : Quarks vs Mesons

Decays of $\Lambda$ in nuclei, nonmesonic mode, are studied by using the $\Lambda N \to NN$ weak transition potential derived from the meson exchange mechanism and the direct quark mechanism. The decay rates are calculated both for the $\Lambda$ in symmetric nuclear matter and light hypernuclei. We consider the exchange of six mesons ($\pi, K, \eta, \rho, \omega, K^\ast$). The form factor in the meson exchange mechanism and short range correlation are carefully studied.Comment: 22 pages, 14 figure

Regular dental visits among hemodialysis patients

AIM To investigate awareness and attitudes about preventive dental visits among dialysis patients; to clarify the barriers to visiting the dentist. METHODS Subjects included 141 dentate outpatients receiving hemodialysis treatment at two facilities, one with a dental department and the other without a dental department. We used a structured questionnaire to interview participants about their awareness of oral health management issues for dialysis patients, perceived oral symptoms and attitudes about dental visits. Bivariate analysis using the χ 2 test was conducted to determine associations between study variables and regular dental check-ups. Binominal logistic regression analysis was used to determine factors associated with regular dental check-ups. RESULTS There were no significant differences in patient demographics between the two participating facilities, including attitudes about dental visits. Therefore, we included all patients in the following analyses. Few patients (4.3%) had been referred to a dentist by a medical doctor or nurse. Although 80.9% of subjects had a primary dentist, only 34.0% of subjects received regular dental check-ups. The most common reasons cited for not seeking dental care were that visits are burdensome and a lack of perceived need. Patients with gum swelling or bleeding were much more likely to be in the group of those not receiving routine dental check-ups (χ 2 test, P < 0.01). Logistic regression analysis demonstrated that receiving dental check-ups was associated with awareness that oral health management is more important for dialysis patients than for others and with having a primary dentist (P < 0.05). CONCLUSION Dialysis patients should be educated about the importance of preventive dental care. Medical providers are expected to participate in promoting dental visits among dialysis patients

Human airway trypsin-like protease in saliva

We first discovered human airway trypsin-like protease (HAT) in human mucoid sputum. Precursor HAT (47 kDa), a cell surface type II transmembrane serine protease, is proteolyzed to mature HAT (27 kDa). Hitherto, HAT has not been detected in other biological fluids except for human sputum. We aimed to clarify whether human saliva contains mature HAT. Trypsin-like protease was isolated from saliva of healthy volunteers by a method adopted for isolation of HAT from sputum using Boc-Phe-Ser-Arg-MCA as the substrate. Biochemical properties of purified protease were similar to those of recombinant HAT (rHAT). HAT concentration in saliva was measured by ELISA, and immunoreactive HAT : total protein ratio (ng/mg) in saliva samples from healthy subjects was similar to that in mucoid sputum. RT-PCR showed that HAT mRNA was expressed in human gingival epithelial cells but not in gingival fibroblasts. Both indirect immunofluorescence and western blotting using monoclonal antibody for α-smooth muscle actin (α-SMA ; a myofibroblast marker) showed that HAT enhanced α-SMA fiber expression in gingival fibroblasts. These results indicate that both mucoid sputum and saliva from healthy subjects have similar concentrations of mature HAT, and HAT is related to certain physiological functions and pathological states of myofibroblasts in the oral cavity