On a retailer’s EOQ in a supply chain with two-level trade credit

Recently, Teng and Goyal [Journal of the Operational Research Society, Vol. 58, pp. 1252-1255, 2007.] extended and modified Huang’s model [Journal of the Operational Research Society, Vol. 54, pp. 1011-1015, 2003.] to develop their model and established the proper theoretical results to obtain the optimal solution. Their inventory model is correct and interesting. However, they give the optimal solutions showing that Theorems 1 and 2 in Teng and Goyal are not complete. The main purpose of this paper is to overcome Teng and Goyal’s shortcomings and to present complete proofs of their Theorems 1 and 2

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML

利用紅球菌變異株降解固醇生產雄二烯二酮之研究

現今工業生產上，主要係利用3-酮類固醇9α-羥基化酵素活性缺失的突變Mycobacterium菌株，將固醇粗原料以生物發酵方式轉換生成17-酮類固醇 [雄烯二酮 (androstenedione, AD) 和雄二烯二酮 (androstadienedione, ADD)]，此可作為類固醇藥物生產的前驅物，以利下游產物合成。3-酮類固醇-9α-羥基化酵素是由kshA (末端氧化酶) 及kshB (還原酶) 兩個組元所組成，本研究室已將對於固醇具有高耐受性的紅球菌 (Rhodococcus sp.)，利用基因重組法將KshB剔除，產生一株能將膽固醇轉換成ADD的基因剔除菌株。實驗首先對此菌株進行發酵條件之優化，探討以植物固醇為唯一碳源，從培養基的主要成分、溫度、改善固醇粗原料的親水性以及添加界面活性劑，來提高固醇粗原料之轉換率。優化培養基 (植物固醇粗原料 5 g/L, K2HPO4 0.5 g/L, KCl 1 g/L, MgSO4 0.5 g/L, Yeast extract 10 g/L, Tween 20 5 g/L) 在28oC下於50 mL尖底離心管中培養7天後，ADD累積量為0.136 mg/mL，莫耳轉換率為3.96%。為提高固醇粗原料的使用量及增加ADD累積量，採用紫外光進行人工變異，挑選在95% 致死率條件下，可快速生長於0.5% 植物固醇平板培養基的菌落。篩選共獲得347顆菌株，當中UV1菌株之ADD累積量在上述優化培養基中最高可達到0.269 mg/mL，莫耳轉換率為7.85%。未來將嘗試利用發酵槽進行擴大規模培養，以期實際應用於發酵工業上類固醇藥物之製備。Pharmaceutical industries utilize mutant strains of Mycobacterium that lack 3-ketosteroid 9α-hydroxylase (KshAB) activity to produce 4-androstene-3,17-dione (AD) or 1,4-androstadiene-3,17-dione (ADD), the precursors for the synthesis of a variety of steroid drugs. In a previous work, a KshB knockout strain of Rhodococcus sp. was created in our laboratory, and it was demonstrated that this strain is able to efficiently convert cholesterol into ADD (unpublished data). In the present study, the ability of this knockout strain to transform phytosterols to ADD in various culture conditions, such as different medium formulation and culture temperature, were investigated. ADD concentration in optimized medium (0.5% phytosterol, 0.05% K2HPO4, 0.1% KCl, 0.05% MgSO4, 1% yeast extract and 0.5% Tween 20) reached 0.136 mg per mL of culture medium, 4% molar conversion, after a week of culture at 28oC. To improve the conversion yield, this knock out strain was further subjected to mutagenesis by UV irradiation. Several UV-induced mutants were selected according to the fact that they grew faster than the original knockout strain on phytosterol containing medium. Of the mutants, UV1 strain produced ADD in optimized medium up to 0.269 mg/mL, 7.9% molar conversion rate. In the future, the cultural conditions will be examined in larger scales in order to produce ADD in industrial levels.中文摘要 i 英文摘要 ii 目次 iii 圖目次 v 表目次 vi 第一章、前言 1一、類固醇 1 二、類固醇藥物之製造合成 2 三、固醇粗原料之微生物降解 2 四、固醇粗原料之微生物降解的主要困難 4 五、目前已知提高類固醇之微生物轉化效率方式 4 六、3-酮類固醇-9α-羥基化酵素 (3-ketosteroid-9α-hydroxylase) 5 七、紅球菌簡介與相關育種研究 6 八、研究目的 7 第二章、材料與方法 8一、實驗菌株 8 二、培養基 8 三、原料與藥品 10 四、膽固醇懸浮液之配製 10 五、植物固醇懸浮液之配製 10 六、種菌培養方法 10 七、生產培養基之探討 10 八、紫外光誘導變異株之前處理 11 九、紫外光誘導變異株之誘導 11 十、菌體總蛋白質量之定量分析 11 十一、類固醇化合物之定性分析 12 十二、類固醇化合物之定量分析 12 十三、HPLC分析植物固醇組成分 13 十四、ADD莫耳回收率之計算 13 第三章、結果 14 第一節、母株與KO菌株生物轉換對固醇粗原料添加之探討 一、母株與KO菌株之生長曲線比較 14 二、KO菌株之碳骨架轉換 14 三、膽固醇原料濃度對產物ADD生物轉換之影響 14 四、不同固醇粗原料與培養天數對產物ADD生物轉換之影響 15 第二節、KO菌株發酵條件之優化 一、固醇懸浮液顆粒大小對產物ADD生物轉換之影響 15 二、界面活性劑對產物ADD生物轉換之影響 16 三、酵母菌萃取物培養基對於產物ADD生物轉換之影響 16 四、額外碳源對於產物ADD生物轉換之影響 17 第三節、KO菌株之紫外光誘變選殖 一、紫外光致死率曲線 17 二、紫外光誘變篩選 18 三、母株、KO菌株與UV1菌株之生長曲線比較 18 四、KO菌株與UV1菌株之培養狀況探討 18 第四章、討論 20 第五章、參考文獻 23 一、中文文獻 23 二、英文文獻 2

Impact of Silent Infarction on the Outcome of Stroke Patients

Silent infarcts (SIs) are commonly found on brain computed tomography (CT) or magnetic resonance imaging (MRI) among elderly subjects, but their risk factors and impact on outcome in stroke patients are unknown. We evaluated the prevalence, risk factors and impact of SIs on the outcome of patients admitted with first-ever ischemic stroke or transient ischemic attack (TIA). Methods: A prospective study of 446 patients admitted consecutively to the neurology service with a diagnosis of TIA or stroke between July 2003 and June 2005, including 226 without any history of prior TIA or stroke. All patients underwent brain CT on the day of admission to the hospital. Risk factors analyzed included age, history of hypertension, diabetes mellitus, cardiovascular disease or stroke, smoking habit and alcohol use. Cholesterol and triglyceride levels were measured on the second day of admission. We monitored these patients for 24 months after stroke onset. Results: The frequency of SIs among the 226 patients with first-ever stroke or TIA was 20%. Most of the SIs were small and deep. Small-artery disease was more frequently observed in patients with SIs. Age, hypertension, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, alcohol use, smoking habits and atrial fibrillation did not significantly differ between patients with SIs and those without SIs. During the 24-month follow-up period, the frequency of recurrent stroke was higher in patients with SIs than those without SIs. The mortality rate was higher in patients without SIs than those with SIs. The interval from stroke onset to rehospitalization was shorter in patients without SIs than in those with SIs. Conclusion: The study showed a higher frequency of small artery disease in patients with SIs. First-ever stroke patients with SIs should be considered at high risk for recurrent stroke

Pregnane-Type Steroids from the Formosan Soft Coral Scleronephthya flexilis

Three pregnane-type steroids, including a new metabolite, 3β-methoxy-5,20-pregnadiene (1) along with two known analogues, 3β-acetoxy-5,20-pregnadiene (2) and 5α-pregna-1,20-dien-3-one (3) were isolated from the soft coral Scleronephthya flexilis. Standard spectroscopic techniques were used to determine the structure of new steroid 1. The absolute stereochemistry of steroid 2 was confirmed by X-ray diffraction analysis. Steroid 3 exhibited potent activity against MOLT-4 tumor cells

Secondary Metabolites with Anti-Inflammatory Activities from One Actinobacteria Amycolatopsis taiwanensis

Phytochemical investigation and chromatographic separation of extracts from one new actinobacteria strain Amycolatopsis taiwanensis that was isolated from soil of Yilan township, in the north of Taiwan, led to the isolation of nine new compounds, amycolataiwanensins A–I (1–9, resp.), and one new natural product, namely amycolataiwanensin J (10). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3, 5, 7 and 8 exhibited potent anti-NO production activity, with IC50 values of 17.52, 12.31, 17.81 and 13.32 μM, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.94 μM. This is the first report on indole metabolite from the genus Amycolatopsis

Effects of EZH2 polymorphisms on susceptibility to and pathological development of hepatocellular carcinoma.

The enhancer of zeste 2 (EZH2) gene encodes the histone methyltransferase that is the catalytic component of the polycomb repressive complex-2, which initiates epigenetic silencing of genes. The expression level of EZH2 in hepatocellular carcinoma (HCC) is highly correlated with tumor progression; however, it has not been determined if specific EZH2 genetic variants are associated with the risk of HCC. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with HCC susceptibility and its clinicopathologic characteristics.A total of 220 HCC patients and 552 cancer-free controls were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, the individuals carrying at least one C allele at EZH2 rs6950683 and rs3757441 had a 0.611-fold and a 0.660-fold lower risk of developing HCC than did wild-type (TT) carriers, respectively. The CCCA or CCTA haplotype among the four EZH2 sites (rs6950683, rs2302427, rs3757441, and rs41277434), respectively, was also associated with a reduced risk of HCC. Furthermore, HCC patients who carried at least one C allele at rs6950683 or rs3757441 had a higher lymph-node-metastasis risk but a lower liver-cirrhosis risk than did patients carrying the wild-type allele.The rs6950683 and rs3757441 polymorphic genotypes of EZH2 might contribute to the prediction of susceptibility to and pathological development of HCC. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of HCC in Taiwan

Saccharpiscinols A–C: Flavans with Potential Anti-Inflammatory Activities from One Actinobacteria Saccharomonospora piscinae

Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A–C (1–3, respectively), and three new natural products, namely (2S)-5,7,3′,4′-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4–6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production