A technique for improving readability of Forrester diagram in system dynamics

We describe a three-pass algorithm for improving the readability of Forrester Diagram in system dynamics. The first pass converts Forrester Diagram to recurrent hierarchy. The second pass sorts the vertices on each level, with the goal of minimizing crossings. The third pass is a finite tuning of the layout that determines the horizontal positions of vertices. An illustrative example is given to verify the result.

KaiC CII Ring Flexibility Governs the Rhythm of the Circadian Clock of Cyanobacteria

The circadian clock orchestrates metabolism and cell division and imposes important consequences to health and diseases, such as obesity, diabetes, and cancer. It is well established that phosphorylation-dependent circadian rhythms are the result of circadian clock protein interactions, which regulate many intercellular processes according to time of day. The phosphorylation-dependent circadian rhythm undergoes a succession of phases: Phosphorylation Phase → Transition Phase → Dephosphorylation Phase. Each phase induces the next phase. However, the mechanism of each phase and how the phosphorylation and dephosphorylation phases are prevented from interfering with each other remain elusive. In this research, we used a newly developed isotopic labeling strategy in combination with a new type of nuclear magnetic resornance (NMR) experiment to obtain the structural and dynamic information of the cyanobacterial KaiABC oscillator system. This system is uniquely suited for the mechanistic studies: mixing KaiA, KaiB KaiC, and ATP generates a self-sustained ~24 h rhythm of KaiC phosphorylation in vitro. Our data strongly suggest that the dynamic states of KaiC underpin the timing mechanism of cyanobacterial oscillator

The significance of seizures and other predictive factors during the acute illness for the long-term outcome after bacterial meningitis

SummaryBackgroundSeizures are important neurological complications of bacterial meningitis, but no information about its epidemiology and the outcomes of seizures after community-acquired bacterial meningitis (CABM) in an adult population have been reported.AimsTo determine the frequency, clinical relevance, subtypes of seizures during the acute phase of bacterial meningitis, and the long-term outcomes of seizure complicating adult CABM.MethodsIn this 12-year retrospective study, 117 adult patients were identified with culture-proven CABM. A comparison was made between the clinical data of the patients with and without seizures during hospitalization.ResultsThirty-one patients had seizures during CABM, accounting for 27% (31/117) of the episodes. The time interval between the onset of bacterial meningitis and the seizures was 1–21 days (mean, 4 days). Furthermore, 80% (25/31) of the episodes occurred within 24h of presentation. Ten patients who had seizures progressed to status epilepticus. At follow-up after completing treatment, 10 patients completely recovered and were seizure-free, 19 died of meningitis during the acute stage and the other two progressed to chronic epilepsy.ConclusionA log-rank test demonstrated that the long-term outcome of adult CABM with acute seizures produced worse outcomes than for those who had no seizures, though no difference was noted between focal and generalized seizures. None of our patients without seizures in the acute phase of bacterial meningitis developed late seizures during the follow-up periods. Poor outcome in this study may attribute to neurological complications such as seizure, hydrocephalus, infection itself, or a combination of complications

Mutation and Lineage Analysis of DNMT3A in BCR-ABL1-negative Chronic Myeloproliferative Neoplasms

SummaryIn addition to the JAK2 V617F mutation, somatic mutation in DNMT3A has been described in BCL-ABL1-negative myeloproliferative neoplasms (MPNs). We have screened for DNMT3A exon 23 mutations in 130 adult Taiwanese patients with chronic phase myeloproliferative neoplasms. Only one somatic DNMT3A R882H mutation was identified in one JAK2 V617F mutation-positive essential thrombocythemia patient (1/91, 1%). Both mutations were detected in the CD34+-, CD19+-, peripheral blood mononuclear cell- and granulocyte-enriched fractions, but were not detected in the CD3+-enriched fraction by lineage analysis. Our findings suggest that DNMT3A mutation is not prevalent in MPNs, and further study is needed to clarify its role in the molecular pathogenesis of myeloproliferative neoplasms

Gene-Gene and Gene-Environmental Interactions of Childhood Asthma: A Multifactor Dimension Reduction Approach

Background: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. Methodology/Principal Findings: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 singlenucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83 % with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance

Somatic Embryogenesis and Sodium Azide Mutagenesis in Oncidium

文心蘭(Oncidium spp.)為高經濟花卉作物，但品種單一化問題亟待克服，以提高台灣在市場之競爭力。本研究以無菌苗葉片、擬圓球體(protocorm like body, PLB)、團狀PLB、幼嫩與成熟莖段、白化苗等為培植體，於添加TDZ之 1/2 MS培養基進行培養，建立體胚發生，並以此再生系統探討疊氮化鈉 ( NaN3 ) 誘變之最適條件，期能建立高效率的誘變系統以增加文心蘭種原之變異性。TDZ 顯著抑制葉片褐化並提升存活率，1.0 mg/L TDZ 可提高葉片、幼嫩莖段之體胚形成數目。擬圓球體可利用橫切處理降低芽體的產生，提高擬圓球體的誘導效率；團狀PLB處理方式仍無法去除已形成之二次體胚。成熟莖段之培植體於黑暗下培養7 週後，切面位置可誘導擬圓球體形成，持續光照環境下培養6 週後，體胚可順利轉綠再生成芽體。同樣方式可誘導側芽形成白化苗，培養在含0.1 mg/L TDZ之 1/2 MS培養基， 3 天即可發現細胞活化現象，黑暗下培養35 天時，可自表皮胚性細胞誘導體胚發生，體胚移至光照培養皆可正常抽芽發根，再生成完整植株，誘導效率穩定。 疊氮化鈉添加於固體培養基方式處理對擬圓球體並無明顯傷害或致死效應；經由液態方式處理，對培植體效果較佳。單一擬圓球體切割處理方式對培殖體傷害過大，不同文心蘭品種之莖段對疊氮化鈉耐受性呈現差異。白化莖段經疊氮化鈉處理，其致死率、誘導率、體胚形成率及體胚形成數隨著處理時間及濃度增加而降低，且在品種、時間及濃度三者間皆呈顯著交感效應。致死率對處理濃度為三次效應，顯示有處理門檻劑量存在，一旦超過此劑量，存活率便會大幅下降。文心蘭 ‘Tariflor Ruby’ 品種依據莖段培植體誘變系統已獲得 6,000 株可能的突變株，觀察M1 幼苗外表性狀，發現有葉形、葉色、株型等性狀變異產生。外表型調查發現，對照組自發突變率為0.83%，在誘變處理下5 單位劑量 (濃度 × 時間) 即發現有4.61 % 之誘變率，在接下來之劑量觀察中，誘變率介於3.23% 與5.17 % 間，誘變率顯示並未隨著劑量效應提高而顯著增加。莖段及白化苗培植體可高效率的誘導產生一致性的體胚，而經疊氮化鈉處理之莖段，可成功誘導擬圓球體並再生植株，產生大量外表型變異植株，為一穩定且高效率的誘變系統。Oncidium orchids are economically important ornamental flower and show high marketing potentiality. However the available variety is still very limited for commercialization. Oncidium leaf, mature stem, PLB and etiolated stem of in vitro seedling were chosen to be explants and cultured on the ½ MS medium with TDZ. The PLB could be induced from all the explants directly and the regeneration system was developed for Oncidium mutagenesis. Leaf and inmature stem supplemented with 1.0 mg/L TDZ produced a large number of PLB. The transversely dissected PLB induced PLB more effective than the vertically did. The PLB protruded from the wounded surface of stem in dark condition following transplanted to light condition for six weeks and shoot regenerated. Bud protruded from the wounded stem surfaces could form etolated seedling. Segments were dissected from the etiolated seedling and cultured on the MS medium supplemented with 1.0 mg/L TDZ , and PLB could be induced directly from the epidermal and sub-epidermal layers after 3 weeks. PLBs could be regenerated from stems explants treated with NaN3. Oncidium PLB, stem and etiolated seeding shown various responses in survival rate in NaN3 mutagenesis. The etolated seedling survival rate and embryo formation demonstrated high correlation with NaN3 concentration and time treatment. Many mutated traits including leaf shape, leaf color, and plant types were observed in the M1 generation. The spontaneous somatic mutation rate is 0.83%, however, the mutation rate of the NaN3-treated seedings ranged from 3.23 % to 5.17 % according to phynotype observation. In conclusion, our results demonstrated that stem and etiolated seedling can be applied to generate uniform somatic embryos efficiently. The NaN3-treated stem can induce PLB, regenerate, and develop to plantlets with high survival rate.中文摘要......i Abstract......iii 目錄..........v 表目錄........vi 圖目錄........vii 緒言..........1 前人研究......3 材料與方法....13 結果..........24 討論..........81 參考文獻......9