Cooperative Fuzzy Games Approach to Setting Target Levels of ECs in Quality Function Deployment

Quality function deployment (QFD) can provide a means of translating customer requirements (CRs) into engineering characteristics (ECs) for each stage of product development and production. The main objective of QFD-based product planning is to determine the target levels of ECs for a new product or service. QFD is a breakthrough tool which can effectively reduce the gap between CRs and a new product/service. Even though there are conflicts among some ECs, the objective of developing new product is to maximize the overall customer satisfaction. Therefore, there may be room for cooperation among ECs. A cooperative game framework combined with fuzzy set theory is developed to determine the target levels of the ECs in QFD. The key to develop the model is the formulation of the bargaining function. In the proposed methodology, the players are viewed as the membership functions of ECs to formulate the bargaining function. The solution for the proposed model is Pareto-optimal. An illustrated example is cited to demonstrate the application and performance of the proposed approach

Factors in the occurrence and restoration of hypoparathyroidism after total thyroidectomy for thyroid cancer patients with intraoperative parathyroid autotransplantation

IntroductionPostoperative hypoparathyroidism (POH) is the most common and important complication for thyroid cancer patients who undergo total thyroidectomy. Intraoperative parathyroid autotransplantation has been demonstrated to be essential in maintaining functional parathyroid tissue, and it has clinical significance in identifying essential factors of serum parathyroid hormone (PTH) levels for patients with parathyroid autotransplantation. This retrospective cohort study aimed to comprehensively investigate influential factors in the occurrence and restoration of POH for patients who underwent total thyroidectomy with intraoperative parathyroid autotransplantation (TTIPA).MethodThis study was conducted in a tertiary referral hospital, with a total of 525 patients who underwent TTIPA. The postoperative serum PTH levels were collected after six months, and demographic characteristics, clinical features and associated operative information were analyzed.ResultsA total of 66.48% (349/525) of patients who underwent TTIPA were diagnosed with POH. Multivariate logistic regression indicated that Hashimoto’s thyroiditis (OR=1.93, 95% CI: 1.09-3.42), P=0.024), the number of transplanted parathyroid glands (OR=2.70, 95% CI: 1.91-3.83, P<0.001) and postoperative blood glucose levels (OR=1.36, 95% CI: 1.06-1.74, P=0.016) were risk factors for POH, and endoscopic surgery (OR=0.39, 95% CI: 0.22-0.68, P=0.001) was a protective factor for POH. Multivariate Cox regression indicated that PTG autotransplantation patients with same-side central lymph node dissection (CLND) (HR=0.50; 95% CI: 0.34-0.73, P<0.001) demonstrated a longer time for increases PTH, and female patients (HR=1.35, 95% CI: 1.00-1.81, P=0.047) were more prone to PTH increases. Additionally, PTG autotransplantation with same-side CLND (HR=0.56, 95% CI: 0.38-0.82, P=0.003) patients had a longer time to PTH restoration, and patients with endoscopic surgery (HR=1.54, 95% CI: 1.04-2.28, P=0.029) were more likely to recover within six months.ConclusionHigh postoperative fasting blood glucose levels, a large number of transplanted PTGs, open surgery and Hashimoto’s thyroiditis are risk factors for postoperative POH in TTIPA patients. Elevated PTH levels occur earlier in female patients and patients without CLND on the transplant side. PTH returns to normal earlier in patients without CLND and endoscopic surgery on the transplant side

Studies on the transcriptional regulation of sterol 12alpha-hydroxylase (CYP8B1)

The conversion of cholesterol into bile acids is mainly via two pathways, which are initiated by CYP7A1 and CYP27A1 respectedly. CYP8B1, a microsomal P450 cytochrome, hydroxylates of the steroid nucleus at the C-12alpha position to form 7alpha, 12alpha-dihydroxy-4-cholesten-3-one, a facultative precursor of CA. The activity of the enzyme determines the ratio between CA and CDCA. The enzyme activity is affected by bile acids, cholesterol, hormones and fasting. In the present studies, we have focused on the structure-function relationship of the rat gene to explore the mechanisms of regulation. The cDNA for rat CYP8B1 coded for a protein of 499 amino acid residues. The gene, like the human and mouse gene, also lacked introns. The promoter region contains several putative transcriptional response elements including DR1, c-jun, NF-1, Sp1 and repeated SRE-1 motifs. Thyroidectomy in rats caused a four-fold increase in CYP8B1 mRNA in the liver together with a 2,2-fold increase of enzyme activity. The treatment of intact animals with L-thyroxine caused a 60% reduction of the enzyme activity and a 50% reduction in CYP8B1 mRNA. No putative DR4 or thyroid hormone response elements could be recognized in the promoter fragment. Previous studies in rats showed that CYP8B1 activity and mRNA levels were increased by fasting and clofibrate. In present studies, fasting for 24 hours or administration of WY-14,643 did not change the CYP8B1 activity and mRNA levels in PPAR-alpha null mice, whereas a significant increase was recorded in wild-type animals. An relative increase of CA was found in the bile. In vitro, PPAR-alpha was found to directly bind to a DR1 motif in the promoter. Co-transfection with PPAR-alpha expression plasmids induced a 2,5-fold increase of the activity of the CYP8B1 promoter in a ligand-dependent manner in Hep G2 cells. Similar to CYP7A1, CYP8B1 is subjected to a negative feed-back regulation by bile acids. Feeding rats with chenodeoxycholic acid caused a 40% decrease of the liver CYP8B1 mRNA levels, while cholestyramine increased the mRNA 120%. It was associated with an increased mRNA levels for FTF and decreased for HNF4-alpha. A bile acid response element (BARE), DR1 motif overlapped with two M binding sites, was identified. FTF strongly repressed the CYP8B1 promoter activity probably by a competitive binding to BARE with HNF4-alpha. In contrast to the up-regulation of CYP7A1, cholesterol feeding of rodents decreases the activity of CYP8B1. Treatment with cholesterol/25-hydroxycholesterol inhibited the activity of the rat CYP8B1 promoter in a dose-dependent manner. Overexpression of SREBPl a and l c stimulated the activity of promoter from rat, mouse and man, while SREBP2 did not have any effects. SREBP1 a and SREBP1 c directly bound to SRE and E box motifs in the rat promoter. Cholesterol feeding also decreased the mRNA levels for SREBP1, but not for SREBP2 in rat liver. In summary, the HNF4-alpha, FTF and PPAR-alpha mediate the regulation of CYP8B1 by bile acids and fatty acids through BARE in the gene promoter. The coordinative effect between HNF4-alpha and FTF seems to be crucial for the expression level of CYP8B. PPAR-alpha mediates the up-regulation of CYP8B1 during starvation and fibrate administration. SREBP1 promotes the transcription of CYP8B1 gene by interaction with SRE and E box motifs, thereby constituting a new regulatory link between the cholesterol and bile acid metabolism. The CYP8B1 gene is also subjected to down-regulation by thyroid hormone, but responsive elements have not yet been identified in the promoter

Dexamethasone pretreatment impairs the thymidylate synthase inhibition mediated flare in thymidine salvage pathway activity in non-small cell lung cancer.

INTRODUCTION:Successful inhibition of thymidylate synthase (TS) by pemetrexed, a TS inhibitor, results in a reproducible transient burst or "flare" in thymidine salvage pathway activity at 2 hrs. of therapy which can be measurable with FLT-PET ([18F]fluorothymidine-positron emission tomography) in non-small cell lung cancer (NSCLC). Routine administration of dexamethasone with pemetrexed-based therapy could potentially confound this imaging approach since dexamethasone is known to inhibit expression of thymidine kinase 1, a key enzyme in the thymidine salvage pathway. Here we examine the potential impact of dexamethasone on the TS inhibition-mediated thymidine salvage pathway "flare" in NSCLC. MATERIALS AND METHODS:In order to determine NSCLC cell line sensitivity to dexamethasone and pemetrexed, IC50 studies were performed on NSCLC cell lines H23, H1975, H460, H1299. TS inhibition-mediated "flare" in thymidine salvage pathway activity was then measured at 2hrs. of exposure to pemetrexed and cisplatin in NSCLC cells lines following using 3H-thymidine incorporation assays under the following conditions: control (no chemotherapy or dexamethasone), or treated with pemetrexed and cisplatin without dexamethasone, with 24 hrs. pre-treatment of dexamethasone or with dexamethasone administered together with chemotherapy. These conditions were chosen to model the delivery of pemetrexed-based therapy in the clinic. RESULTS:The IC50 of H23, H1975, H460, H1299 for dexamethasone and pemetrexed were 40, 5.9, 718, 362 μM and 0.22, 0.73, 0.14 and 0.66 μM respectively. Significant blunting of the thymidine salvage pathway "flare" is observed at 2hrs. of pemetrexed-based therapy when dexamethasone sensitive cell lines H23 and H1975 were pretreated with dexamethasone but not when dexamethasone was given together with pemetrexed therapy or in the setting of dexamethasone resistance (H460 and H1299). CONCLUSION:24 hr. pretreatment with dexamethasone, but not same day co-administration of dexamethasone with therapy, impairs the TS inhibition-mediated "flare" in thymidine salvage pathway activity in NSCLC

Restoring KLF5 in Esophageal Squamous Cell Cancer Cells Activates the JNK Pathway Leading to Apoptosis and Reduced Cell Survival

Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC

Detection and Identification of extra virgin olive oil adulteration by GC-MS combined with chemometrics

In this study, an analytical method for the detection and identification of extra virgin olive oil adulteration with four types of oils (corn, peanut, rapeseed, and sunflower oils) was proposed. The variables under evaluation included 22 fatty acids and 6 other significant parameters (the ratio of linoleic/linolenic acid, oleic/linoleic acid, total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), MUFAs/PUFAs). Univariate analyses followed by multivariate analyses were applied to the adulteration investigation. As a result, the univariate analyses demonstrated that higher contents of eicosanoic acid, docosanoic acid, tetracosanoic acid, and SFAs were the peculiarities of peanut adulteration and higher levels of linolenic acid, 11-eicosenoic acid, erucic acid, and nervonic acid the characteristics of rapeseed adulteration. Then, PLSLDA made the detection of adulteration effective with a 1% detection limit and 90% prediction ability; a Monte Carlo tree identified the type of adulteration with 85% prediction ability

Interspecific chloroplast genome sequence diversity and genomic resources in Diospyros

Abstract Background Fruits of persimmon plants are traditional healthy food in China, Korea and Japan. However, due to the shortage of morphological and DNA markers, the development of persimmon industry has been heavily inhibited. Results Chloroplast genomes of Diospyros cathayensis, D. virginiana, D. rhombifolia and D. deyangensis were newly sequenced. Comparative analyses of ten chloroplast genomes including six previously published chloroplast genomes of Diospyros provided new insights into the genome sequence diversity and genomic resources of the genus. Eight hyper-variable regions, trnH-psbA, rps16-trnQ, rpoB-trnC, rps4-trnT-trnL, ndhF, ndhF-rpl32-trnL, ycf1a, and ycf1b, were discovered and can be used as chloroplast DNA markers at/above species levels. The complete chloroplast genome sequences provided the best resolution at inter-specific level in comparison with different chloroplast DNA sequence datasets. Conclusion Diospyros oleifera, D. deyangensis, D. virginiana, D. glaucifolia, D. lotus and D. jinzaoshi are important wild species closely related to the cultivated persimmon D. kaki. The hyper-variable regions can be used as DNA markers for global genetic diversity detection of Diospyros. Deeper study on these taxa would be helpful for elucidating the origin of D. kaki