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Rong, Haina, Kang Yi, Gexiang Zhang, Jianping Dong, Prithwineel Paul, and Zhiwei Huang. "Automatic Implementation of Fuzzy Reasoning Spiking Neural P Systems for Diagnosing Faults in Complex Power Systems." Complexity 2019 (June 19, 2019): 1–16. http://dx.doi.org/10.1155/2019/2635714.
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As an important variant of membrane computing models, fuzzy reasoning spiking neural P systems (FRSN P systems) were introduced to build a link between P systems and fault diagnosis applications. An FRSN P system offers an intuitive illustration based on a strictly mathematical expression, a good fault-tolerant capacity, a good description for the relationships between protective devices and faults, and an understandable diagnosis model-building process. However, the implementation of FRSN P systems is still at a manual process, which is a time-consuming and hard labor work, especially impossible to perform on large-scale complex power systems. This manual process seriously limits the use of FRSN P systems to diagnose faults in large-scale complex power systems and has always been a challenging and ongoing task for many years. In this work we develop an automatic implementation method for automatically fulfilling the hard task, named membrane computing fault diagnosis (MCFD) method. This is a very significant attempt in the development of FRSN P systems and even of the membrane computing applications. MCFD is realized by automating input and output, and diagnosis processes consists of network topology analysis, suspicious fault component analysis, construction of FRSN P systems for suspicious fault components, and fuzzy inference. Also, the feasibility of the FRSN P system is verified on the IEEE14, IEEE 39, and IEEE 118 node systems.
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Parker, Scott L., and Matthew J. McGirt. "Determination of the Minimum Improvement in Pain, Disability, and Health State Associated With Cost-Effectiveness." Neurosurgery 71, no. 6 (September 14, 2012): 1149–55. http://dx.doi.org/10.1227/neu.0b013e318271ebde.
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ABSTRACT BACKGROUND: Minimum clinical important difference (MCID) has been adopted as the smallest improvement in patient-reported outcome needed to achieve a level of improvement thought to be meaningful to patients. OBJECTIVE: To use a common MCID calculation method with a cost-utility threshold anchor to introduce the concept of minimum cost-effective difference (MCED). METHODS: Forty-five patients undergoing transforaminal lumbar interbody fusion for degenerative spondylolisthesis were included. Outcome questionnaires were administered before and 2 years after surgery. Total cost per quality-adjusted life-year (QALY) gained was calculated for each patient. MCED was determined from receiver-operating characteristic curve analysis with a cost-effective anchor of < $50 000/QALY and < $75 000/QALY. MCID was determined with the health transition item as the anchor. RESULTS: Significant improvement was observed 2 years after transforaminal lumbar interbody fusion for all outcome measures. Mean total cost per QALY gained at 2 years was $42 854. MCED was greater than MCID for each outcome measure, meaning that a greater improvement was required to represent cost-effectiveness than a clinically meaningful improvement to patients. The area under the receiver-operating characteristic curve was consistently ≥ 0.70 with both cost-effective anchors, suggesting that outcome change scores were accurate predictors of cost-effectiveness. Mean cost per QALY gained was significantly lower for patients achieving compared with those not achieving an MCED in visual analog scale for leg pain ($43 560 vs $112 087), visual analog scale for back pain ($41 280 vs $129 440), Oswestry Disability Index ($30 954 vs $121 750), and EuroQol 5D ($35 800 vs $189 412). CONCLUSION: MCED serves as the smallest improvement in an outcome instrument that is associated with a cost-effective response to surgery. With the use of cost-effective anchor of < $50 000/QALY, MCED after transforaminal lumbar interbody fusion was 4 points for visual analog scale for low back pain, 3 points for visual analog scale for leg pain, 22 points for Oswestry Disability Index, and 0.31 QALYs for EuroQol 5D.
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Patruno, Rosa, Ilaria Marech, Nicola Zizzo, Michele Ammendola, Patrizia Nardulli, Claudia Gadaleta, Marcello Introna, et al. "C-Kit Expression, Angiogenesis, and Grading in Canine Mast Cell Tumour: A Unique Model to Study C-Kit Driven Human Malignancies." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/730246.
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Canine cutaneous mast cell tumour (CMCT) is a c-Kit driven tumour sharing similar c-Kit aberrations found in human gastrointestinal stromal tumour. CMCT is classified into three forms: well- (G1), intermediately (G2) (more benign diseases), and poorly (G3) differentiated (malignant) forms. We assess a correlation between c-Kit status, grading, and angiogenesis in CMCTs to explore their potential significance in humans. C-Kit receptor (c-KitR) expression, microvascular density (MVD), and mast cell granulated and degranulated status density (MCGD and MCDD, resp.) were analyzed in 97 CMCTs, by means of histochemistry, immunohistochemistry double staining, and image analysis system. Data showed that predominantly diffuse cytoplasmic- and predominantly focal paranuclear- (Golgi-like) c-Kit protein (PDC-c-Kit and PFP-c-Kit, resp.) expression correlate with high MVD, G3 histopathological grade, and MCDD. Moreover, predominant cell membrane-c-KitR (PCM-c-KitR) expression status correlates with low MVD, G1-G2 histopathological grade, and MCGD. These findings underline the key role of c-Kit in the biopathology of canine MCTs, indicating a link between aberrant c-Kit expression, increased angiogenesis, and higher histopathological grade. CMCT seems to be a model to study contributions of c-Kit activated MCs in tumour angiogenesis and to evaluate the inhibition of MCs activation by means of c-Kit tyrosine kinase inhibitors, currently translated in humans.
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Duan, Lei, Sarah Calhoun, Daeun Shim, Ricardo E. Perez, Lothar A. Blatter, and Carl G. Maki. "Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells." Journal of Molecular Cell Biology 13, no. 6 (March 23, 2021): 433–44. http://dx.doi.org/10.1093/jmcb/mjab018.
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Abstract Tamoxifen (TAM) is the first-line endocrine therapy for estrogen receptor-positive (ER+) breast cancer (BC). However, acquired resistance occurs in ∼50% cases. Meanwhile, although the PI3K/AKT/mTOR pathway is a viable target for treatment of endocrine therapy-refractory patients, complex signaling feedback loops exist, which can counter the effectiveness of inhibitors of this pathway. Here, we analyzed signaling pathways and metabolism in ER+ MCF7 BC cell line and their TAM-resistant derivatives that are co-resistant to endoxifen using immunoblotting, quantitative polymerase chain reaction, and the Agilent Seahorse XF Analyzer. We found that activation of AKT and the energy-sensing kinase AMPK was increased in TAM and endoxifen-resistant cells. Furthermore, ERRα/PGC-1β and their target genes MCAD and CPT-1 were increased and regulated by AMPK, which coincided with increased fatty acid oxidation (FAO) and autophagy in TAM-resistant cells. Inhibition of AKT feedback-activates AMPK and ERRα/PGC-1β-MCAD/CPT-1 with a consequent increase in FAO and autophagy that counters the therapeutic effect of endoxifen and AKT inhibitors. Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.
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Nantavithya, Chonnipa, Kitwadee Saksornchai, Puntiwa Oonsiri, and Kanjana Shotelersuk. "Dosimetric study of three-dimensional conformal radiotherapy, electronic compensator technique, intensity-modulated radiation therapy and volumetric-modulated arc therapy in whole breast irradiation." Journal of Radiotherapy in Practice 16, no. 4 (May 9, 2017): 431–43. http://dx.doi.org/10.1017/s1460396917000243.
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AbstractBackgroundWhole breast irradiation is an essential treatment after breast-conserving surgery (BCS). However, there are some adverse effects from inhomogeneity and dose to adjacent normal tissues.ObjectiveAim of this study was to compare dosimetry among standard technique, three-dimensional conformal radiotherapy (3D-CRT), and advanced techniques, electronic compensator (ECOMP), inverse intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT).MethodsWhole breast irradiation treatment plans of patients who had underwent BCS and whole breast irradiation were re-planned with all four techniques. Clinical target volume was contoured according to the Radiation Therapy Oncology Group atlas for breast only in patients who had negative node or ductal carcinoma in situ and breast with chest wall for patients with positive node. Planning target volume was non-uniformly expanded. Dose prescription was 50 Gy in 25 fractions with 6 MV photon energy.ResultsIn total, 25 patients underwent whole breast irradiation with computed tomography simulation from November 2013 to November 2014 were included. Six patients with positive nodes were re-planned for breast with chest wall irradiation and 19 patients with negative nodes were re-planned for breast only irradiation. Primary outcome, radical dose homogeneity index (HI) of 3D-CRT, ECOMP, IMRT and VMAT were 0·865, 0·889, 0·890 and 0·866, respectively. ECOMP and IMRT showed significant higher HI than 3D-CRT (p-value<0·001). Secondary outcome, conformity index (CI) of advanced technique were significantly better than 3D-CRT. Lung V20, mean ipsilateral lung dose (MILD), mean heart dose (MHD), heart V25, heart V30 of advanced techniques were also lower than 3D-CRT. ECOMP had better mean lung dose (MLD), mean contralateral lung dose (MCLD) and mean contralateral breast dose (MCBD) when compared with 3D-CRT. Monitor units of advanced techniques were significantly higher than 3D-CRT.ConclusionsHI of ECOMP and IMRT were significantly higher than 3D-CRT technique. All advanced techniques showed statistically better in CI. Lung V20, MILD, heart V25 and heart V30 of advanced techniques were lower than 3D-CRT. However, only ECOMP showed decreased MLD, MHD, MCLD and MCBD when compared with 3D-CRT.
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Chong, C. L. G., Faizah Othman, and Farida Hussan. "Vascular Protective Effects of Morinda citrifolia Leaf Extract on Postmenopausal Rats Fed with Thermoxidized Palm Oil Diet: Evidence at Microscopic Level." International Journal of Vascular Medicine 2018 (September 5, 2018): 1–10. http://dx.doi.org/10.1155/2018/6317434.
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Atherosclerosis is now well understood as an inflammatory disease instead of lipid storage disorder; however, the conventional treatment is not targeted on treating the inflammation. Morinda citrifolia L. (Rubiaceae) leaf or noni leaf, which is a medicinal food (ulam) used in Traditional Malay Medicine to prevent chronic diseases, may have the potential to be formulated into a functional antiatherosclerotic agent. This study aimed to investigate the effectiveness of Morinda citrifolia leaf extract (MCLE) treatment at histological and ultrastructural level, comparing it with Simvastatin. Thirty-eight female Sprague Dawley rats were divided into five groups: Sham (Sham), ovariectomized (OVX), ovariectomized with Simvastatin 10 mg/kg (OVX+ST), ovariectomized with low dose MC 500 mg/kg (OVX+MCLD), and ovariectomized with high dose MC 1000 mg/kg (OVX+MCHD). Atherosclerosis was induced by producing oestrogen deficiency through ovariectomy and feeding with thermoxidized palm oil (TPO) diet for 12 weeks along with the treatment. The results revealed significantly (P<0.05) lower systolic blood pressure (SBP) in the group treated with MCHD compared to the untreated OVX, whereas the diastolic blood pressure (DBP) was significantly higher in the untreated OVX group compared to the Sham group. Treatment with MCHD also significantly lowered the total cholesterol (TC) level compared to the OVX. The OVX group showed significantly lower high-density lipoprotein (HDL) level compared to the Sham group. The untreated OVX group showed evident histological and ultrastructural features of vascular inflammation such as blood cells accumulation in the lumen, vacuolation of the endothelial cells, subendothelial space widening, elastic fibres disruption, increased intima media thickness (IMT), smooth muscle cells fragmentation, and perivascular adipose tissue (PVAT) deposition. All these pathological changes were less seen in the groups treated with MCLE. In conclusion, we reported the mechanism of antiatherosclerotic property of MCLE through lipids elimination and anti-inflammatory activity. In addition, we do not recommend the use of statin in the absence of dyslipidemia as it causes PVAT deposition.
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Musa, A., H. J. Steeman, and M. De Paepe. "Performance of Internal and External Reforming Molten Carbonate Fuel Cell Systems." Journal of Fuel Cell Science and Technology 4, no. 1 (April 19, 2006): 65–71. http://dx.doi.org/10.1115/1.2393306.
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Molten carbonate fuel cells (MCFC) are a promising alternative power source for distributed or residential power plants. Therefore, thermodynamic models are built in an Aspen customer modeler for the externally reformed (ER) MCFC and internally reformed (IR) MCFC. These models are integrated in Aspen Plus™. In this article the performance of internal and external reforming molten carbonate fuel cell systems are investigated. To this end the gas temperature at the anode inlet is varied to be able to exam the effect of operating temperature on the operating conditions for different modes of MCFC systems in a range between 600 and 700°C. It is found that the operating temperature has more effect on the cell voltage of IR-MCFC system compared to ER-MCFC system. Simulations show that the IR-MCFC system is more efficient than the ER-MCFC system. The cycle efficiency is rather independent of the operating temperature for as well ER-MCFC as IR-MCFC systems.
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Bognár, Erzsébet, Gabriella Hellner, Andrea Radnóti, László Somogyi, and Zsolt Kemény. "Effect of Different Chlorine Sources on the Formation of 3-Monochloro-1,2-Propanediol and 2-Monochloro-1,3-Propanediol Fatty Acid Esters during Frying." Periodica Polytechnica Chemical Engineering 64, no. 4 (September 19, 2019): 523–29. http://dx.doi.org/10.3311/ppch.14137.
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Several studies indicated that chlorine salts provoke 3-monochloro-1,2-propanediol fatty acid esters (3-MCPD-FE) and 2-monochloro-1,3- propanediol fatty acid esters (2-MCPD-FE) formation in oils during frying. The amount of MCPD strongly depends on the type and the amount of chlorine salt. Food raw materials, additives themselves may contain several chlorine compounds, providing precursors for 2- and 3-MCPD-FE formation during frying. Then, the fat uptake can cause measurable concentrations in the fried food as well. This paper aims at screening chlorine compounds occurring in food industry. Influence of sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl2), ferric chloride (FeCl3) and ammonium chloride (NH4Cl) on the formation of MCPD-FE was investigated, mimicking frying conditions (175-180 °C, atmospheric pressure), applying high oleic sunflower oil as frying medium. 2-MCPD-FE and 3-MCPD-FE were determined by using an indirect method based on alkaline-catalyzed transesterification and GC-MS analysis. As expected, the reference sample without using any chlorine salt resulted only slight increase in 3-MCPD-FE concentration, and no increase in 2-MCPD-FE concentration. In case of the stable salts minor formation was observed. At as high as 3 % dosage of NaCl and KCl 1.6 and 2.4 mg/kg 3-MCPD-FE generated, respectively. Adding CaCl2, NH4Cl and FeCl3 resulted in very strong MCPD-FE formation by both isomers (2- and 3-MCPD-FE) in this increasing order. 0.1 % FeCl3 generated 70 mg/kg 2-MCPD-FE and 238 mg/kg 3-MCPD-FE by the end of 8-hour heating.
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Cao, Yong Jie, Ming Xian Liu, Li Hua Gan, Yao Kang Lv, Zi Jie Xu, Zhi Xian Hao, Hong Lai Liu, and Long Wu Chen. "Preparation and Electrochemical Properties of Fluorinated Mesoporous Carbon Foams for Electric Double-Layer Capacitors." Advanced Materials Research 239-242 (May 2011): 3190–93. http://dx.doi.org/10.4028/www.scientific.net/amr.239-242.3190.
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We reported the preparation and electrochemical properties of fluorinated mesoporous carbon foams (F-MCFs) for application as electric double-layer capacitors (EDLCs). By using fluorinated resol which was obtained from the polymerization of formaldehyde, phenol, and 3-fluorophenol as the carbon source and fluorin precursor, and triblock copolymer F127 as a template, F-MCFs were prepared through evaporation induced self-assembly strategy. The F-MCFs were characterized by N2 adsorption and desorption, transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). The results indicate that the F-MCFs possess highly ordered mesostructure with a specific surface area of 675 m2/g, a uniform pore size of 2.2 nm and a pore volume of 0.12 cm3/g. The wettability of F-MCFs was investigated by contact angle analysis. The contact angle of F-MCFs for water is 111.5o, much lower than that of mesoporous carbon foams (MCFs) (141o), indicating that the surface wettability of F-MCFs is improved by the introduction of fluorin into the carbon matrix. The enhancement of wettability would increase the surface contact of electrolyte and electrode and accelerate the ion transfer within the pore channel, and thus improve the electrochemical properties of F-MCFs. The electrochemical properties of the F-MCFs have been investigated by cyclic voltammetry (CV) and galvanostatic charge/discharge in electrolyte of 6 mol/L KOH with a three-electrode system. F-MCFs present linear galvanostatic charge-discharge curve at a loading current of 10 mA, and possess good charge-discharge efficiency over 98%. The specific capacitance of the F-MCFs is 220 F/g, significantly higher than that of the MCFs (140 F/g). F-MCFs show important prospect as electrode materials for the application in EDLCs.
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Rousseau, Aurélie, Patrick Van Dreden, Amir Khaterchi, Elisabeth Mbemba, Annette Larsen, Ismail Elalamy, and Grigorios T. Gerotziafas. "Acquision of Resistance to Doxorubicin By Breast Cancer Cells MCF7 Enhances Their Procoagulant Properties and Alters the Efficacy of Antithrombotic Agents to Inhibit Thrombin Generation." Blood 126, no. 23 (December 3, 2015): 1113. http://dx.doi.org/10.1182/blood.v126.23.1113.1113.
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Abstract Introduction: A major problem associated with breast cancer chemotherapy is the subsequent development of resistance to chemotherapeutic agents (multidrug résistance-MDR). Hypercoagulability, increased risk of venous thromboebolism (VTE) and high rate of failure of the antithrombotic treatment with LMWHs have been observed in patients with disease resistant to the chemotherapy. Aim of the study: In the present study we investigated if acquisition of MDR by breast cancer cells MCF7 is associated with modification of their procoagulant potency and induces alteration of the efficacy of the antithrombotic agents. We evaluated the capacity of wild type MCF7 cells (MCF7/WT) and doxorubicin resistant cells (MCF7/DR) to trigger thrombin generation (TG) and to modify the antithrombotic activity of the LMWH enoxaparin, and the specific direct and indirect FXa inhibitors (apixaban and fondaparinux). Materials and Methods: Pre-treatment of MCF-7 cells for several weeks with increasing concentrations of doxorubicin, induced the acquisition of chemo-resistance phenotype documented by the expression the MDR1-Pgp. Tissue factor (TF) and MDR1-Pgp expression by MCF7/WT and MCF7/DR cells were assessed by flow cytometry and western blot assays. Reverse transcriptase - polymerase chain reaction (RT-PCR) for TF mRNA expression was also performed. Thrombin generation of normal platelet poor plasma (PPP) in the presence of MCF7 cells was assessed with the Calibrated Automate Thrombogram® assay (Diagnostica Stago). TG in the presence of MCF7 cells was also assessed in PPP spiked with clinically relevant concentrations of enoxaparin, apixaban or fondaparinux. The efficiency of the studied agents in the presence of MCF7 cells was compared to that in the control experiment where TG was triggered by PPP-Reagent® 5 pM TF. The antithrombotic agents were compared on the bases of the concentration which inhibited 50% TG (IC50). Results: The MCF7/DR cells showed higher expression of TF as compared to MCF7/WT. The TF expression by MCF7/DR was correlated with the expression of the MDR1/P-gp. The MCF7/DR cells significantly enhanced TG as compared to MCF7/WT cells. The three studied agents significantly inhibited TG at plasma concentrations usually achieved at doses for thromboprophylaxis. The presence resistant MCF7 cells did not significantly modify the antithrombotic potency of fondaparinux. The inhibitory effect of enoxaparin and apixaban on thrombin generation was partially reversed when TG was triggered by MCF7/DR as compared to that triggered by MCF7/WT or in the control experiment. Table 1. Modification of the inhibitory potency of the antithrombotic agents by MCF7 cells on thrombin generation in function of the acquisition of MDR phenotype. IC50 for MRI PPP + TF/PPL PPP + MCF7/WT PPP+ MCF7/DR fondaparinux (anti-Xa IU/mL) 0.21 ± 0.03 0.28 ± 0.06 0.30 ± 0.04 enoxaparin (anti-Xa IU/mL) 0.10 ± 0.02 0.12 ± 0.05 0.23 ± 0.08* apixaban (ng/ml) 14 ± 0.9 19 ± 3.1 26 ± 1.4* *p<0.05 versus MCF7/WT PPL: procoagulant phospholipids MRI: mean rate of the propagation phase of thrombin generation IC50: concentration that inhibits 50% the MRI Conclusions: The acquisition of the chemo-resistance phenotype by the breast cancer cells MCF7 is associated with enhancement of their procoagulant properties. The procoagulant fingerprint of the chemo-resistant MCF7 cells is characterized by increased expression of TF which is correlated with enhanced thrombin generation. The chemo-resistant MCF7 cells reverse the antithrombotic effect of enoxaparin and apixaban but not that of fondaparinux. Disclosures Van Dreden: Diagnostica Stago: Employment.
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Lê Đình, Chi, Thượng Nguyễn Như, Tú Vũ Ngọc, Hồng Hảo Lê Thị, and Sơn Trần Cao. "Xác định đồng thời các dạng ester của 3-MCPD và 2-MCPD trong sữa công thức bằng GC-MS/MS." Heavy metals and arsenic concentrations in water, agricultural soil, and rice in Ngan Son district, Bac Kan province, Vietnam 3, no. 2 (June 10, 2020): 133–44. http://dx.doi.org/10.47866/2615-9252/vjfc.653.
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Nghiên cứu đã phát triển và thẩm định phương pháp xác định đồng thời các dạng ester của 3-MCPD và 2-MCPD trong sữa công thức bằng GC-MS/MS. Các ester của MCPD được chiết từ mẫu sữa công thức bằng hỗn hợp ethanol/n-hexane/diethyl ether (1/1/1, v/v/v), sau đó được xử lý với acid sulfuric để giải phóng dạng tự do. Các chất 3-MCPD và 2-MCPD dạng tự do và nội chuẩn đồng vị 3-MCPD-d5 and 2-MCPD-d5 được dẫn xuất với acid phenylboronic và sau đó dẫn xuất được phân tích bằng GC-MS/MS ở chế độ MRM. Cột tách được sử dụng là cột mao quản DB-5MS, khí mang là Heli ở tốc độ 1 mL/phút. Chế độ MRM đã được sử dụng để lựa chọn 1 ion mẹ và 2 ion con cho mỗi chất phân tích. Kết quả thẩm định cho thấy phương pháp đáp ứng các yêu cầu theo AOAC SMPR. Phương pháp đã được ứng dụng để xác định các ester của 3-MCPD và 2-MCPD trong các mẫu sữa công thức lấy ở một số tỉnh, thành phố của Việt Nam. Có 38,9% số mẫu phát hiện 3-MCPD ester và 34,7% số mẫu phát hiện 2-MCPD ester.
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Doležal, M., P. Calta, and J. Velíšek. "Formation and decomposition of 3-chloropropane-1,2-diol in model systems." Czech Journal of Food Sciences 22, SI - Chem. Reactions in Foods V (January 1, 2004): S263—S266. http://dx.doi.org/10.17221/10677-cjfs.
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Model experiments were carried out using mixtures of 3-chloropropane-1,2-diol (3-MCPD), its precursor glycerol, NaCl, water and an emulsifier. The aim of this study was to simulate formation and decomposition of 3-MCPD at the surface layers of thermally processed foods containing naturally present or intentionally added salt. The formed 3-MCPD levels depend on temperature and reach the maximum value at 230°C. One kg of glycerol gives rise to about 50 mg of 3-MCPD, while about 0.6 mg of 3-MCPD arise at 100°C. The rate constants k<sub>1</sub> of 3-MCPD formation from glycerol and constants k<sub>2</sub> of 3-MCPD decomposition were calculated employing the first order reaction kinetics. The rate constants k<sub>2</sub> of 3-MCPD degradation are higher than the respective constants of its formation. Other kinetic parameters (time of maximum concentration) were also calculated and the achieved results were discussed with respect to levels of 3-MCPD in foods.
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Liu, Zhigang, Chunlei Zheng, Denise E. Sabatino, and Bin Zhang. "The C Domain Mediates the Export of FVIII from the Endoplasmic Reticulum By Interacting with MCFD2." Blood 128, no. 22 (December 2, 2016): 255. http://dx.doi.org/10.1182/blood.v128.22.255.255.
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Abstract Coagulation factor V (FV) and VIII (FVIII) are large plasma glycoproteins important for hemostasis and thrombosis. After undergoing folding and quality control in the endoplasmic reticulum (ER), FV and FVIII are packaged into COPII (coat protein complex-II) vesicles for transport to the Golgi. We have previously shown that packaging of FV and FVIII into COPII vesicles requires a cargo receptor. This receptor is a Ca2+-dependent protein complex formed by LMAN1 and MCFD2, two proteins that cycle between the ER and the cis-Golgi. Mutations in either LMAN1 or MCFD2 cause the combined deficiency of FV and FVIII, a rare bleeding disorder characterized by the reduction of both FV and FVIII to 5-30% of normal. Cargo receptors are thought to be transmembrane proteins that interact with cargo in the ER lumen and with the COPII coat on the cytoplasmic side of the ER. However, it is not clear how this cargo receptor recognizes and transports cargo. The requirement of a soluble protein (MCFD2) is a unique feature that has not been observed in other known cargo receptors. The basic hypothesis in the receptor-mediated ER-to-Golgi transport model is that specific signals are embedded in cargo proteins that are recognized by their cognate receptors. We previously showed that FV and FVIII interact with both LMAN1 and MCFD2. To identify signals in FV and FVIII that are recognized by MCFD2, we performed immunoprecipitation (IP) of Myc-tagged MCFD2 with a series of Flag-tagged FVIII domain deletion mutants. The light chain of FVIII co-immunoprecipitates with MCFD2, using either anti-Myc or anti-Flag antibodies. The co-IP is mediated through the C domain, not the A3 domain of the light chain. When expressed individually, the C1 domain retains strong co-IP with MCFD2, while the C2 domain shows weaker co-IP with MCFD2. Similarly, only the C domain of FV can co-IP with MCFD2, consistent with the notion that the signal recognized by the LMAN1-MCFD2 complex is a common feature shared by FV and FVIII. To confirm the interaction of the C domain with MCFD2, we used the Bimolecular Fluorescence Complementation assay to detect the interaction in situ. MCFD2 and C domain mutants were separately fused to the N-terminal and the C-terminal halves of the yellow fluorescent protein. When the C1 domain and MCFD2 fusion proteins were co-transfected into HeLa cells, fluorescence signals were detected in live cells, indicating that an interaction between the C1 domain and MCFD2. Transfection of the A3 domain of FVIII produced no fluorescence signals. We further found that the C1 domain of the light chain can significantly increase the heavy chain secretion in pulse-chase experiments. To examine the interaction of MCFD2 with FVIII in vivo, we generated transgenic mice expressing the heavy chain (HC) and light chain (LC) of canine FVIII driven by the liver-specific transthyretin promoter that have been bred into the hemophilia A background. Transgene expression is 30-40 ng/ml for HC and 150-250 ng/ml for LC. We crossed these canine FVIII transgenic mice with our MCFD2 knockout mice and obtained the Mcfd2+/+/HC, Mcfd2-/-/HC, Mcfd2+/+/LC and Mcfd2-/-/LC mouse lines, all of which are in the hemophilia A background. HC and LC levels in plasma were measured by canine FVIII-specific ELISA in 3 month-old mice. Results showed that the plasma LC level was 40% lower in Mcfd2-/- / LC mice than that in Mcfd2+/+/ LC mice (P<0.01), while plasma HC was indistinguishable between Mcfd2+/+/HC and Mcfd2-/-/HC mice. These results indicate that efficient LC secretion is dependent on MCFD2 in vivo, consistent with our cell-based results. In conclusion, our results suggest that MCFD2 recognizes sorting signals located in the C1 and C2 domains of FV and FVIII. The identification of such signals validates the specific cargo and cargo receptor pairing and highlights a direct role of MCFD2 in ER-to-Golgi transport of FV and FVIII. Disclosures No relevant conflicts of interest to declare.
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Tian, Yu Dong. "Research of Molten Carbonate Fuel Cells Modeling Based on Neural Computing." Applied Mechanics and Materials 389 (August 2013): 81–84. http://dx.doi.org/10.4028/www.scientific.net/amm.389.81.
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The molten carbonate fuel cell (MCFC) is an important research field of the new energy generation equipment, and is a difficulty in the research field of high-temperature fuel cells at present. To aim at the MCFC modeling problem, the MCFC electrochemical mechanism process was analyzed firstly, then the MCFC modeling applied neural computing is advanced. Thirdly, the structure, algorithm and simulation of MCFC modeling based on feedback neural networks were presented in detail. Finally, the computer simulation and conducted experiment verified that this model was fast and accurate, and can be as a suitable operational model of MCFC real-time control.
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M Breitling-Utzmann, C., H. Hrenn, N. U Haase, and G. M Unbehend. "Influence of dough ingredients on 3-Mcpd formation in toast." Czech Journal of Food Sciences 22, SI - Chem. Reactions in Foods V (January 1, 2004): S25—S28. http://dx.doi.org/10.17221/10605-cjfs.
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The influences of both traditional dough ingredients like fat and salt and a commercially used baking agent on the formation of 3-chloropropane-1,2-diol (3-MCPD) during toasting of bread were investigated. Whereas varying the fat or salt contents within technologically practicable limits showed negligible effects on 3-MCPD formation, the baking agent turned out to have a crucial impact on generating 3-MCPD in toasted bread slices. We found considerable evidence that the baking agent’s main component saccharose was the major cause for its boosting the 3-MCPD formation. Emulsifiers like mono- and diacylglycerols or lecithin did not have any significant influence. 3-MCPD formation showed good correlation with the degree of browning of the bread slices; their 3-MCPD content increased exponentially towards dark brown coloured toasts. The relative proportions between 3-MCPD and 2-MCPD were an average of 3:1 in all samples. Dichloropropanols like e.g. 1,3-dichloropropan-2-ol could not be detected.
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Gao, Boyan, Yanfang Li, Guoren Huang, and Liangli Yu. "Fatty Acid Esters of 3-Monochloropropanediol: A Review." Annual Review of Food Science and Technology 10, no. 1 (March 25, 2019): 259–84. http://dx.doi.org/10.1146/annurev-food-032818-121245.
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Fatty acid esters of 3-monochloropropane-1,2-diol (3-MCPD esters) are a new group of processing-induced chemical toxicants with possible nephrotoxicity and testicular toxicity. 3-MCPD esters have been detected in many food categories, including refined edible oils, bread, coffee, and infant formula. 3-MCPD esters have also been detected in human breast milk, indicating their possible absorption and distribution in human organs and tissues. 3-MCPD esters have become a food safety concern, and in 2013 the European Food Safety Authority estimated a tolerable daily value (TDI) of 2 μg/kg body weight (BW) for the amount of free 3-MCPD. This review summarizes the available information on 3-MCPD ester research, including the analytical methods, exposure biomarkers, absorption and metabolism, toxicities, formation mechanisms, and mitigation strategies as well as the occurrence of 3-MCPD esters in human foods. This review may serve as a scientific foundation for advancing our understanding of 3-MCPD esters and their food safety concerns.
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Divínová, V., M. Doležal, and J. Velíšek. "Free and bound 3-chloropropane-1,2-diol in coffee surrogates and malts." Czech Journal of Food Sciences 25, No. 1 (January 7, 2008): 39–47. http://dx.doi.org/10.17221/735-cjfs.
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The levels are reported of the free 3-chloropropane-1,2-diol (3-MCPD), its bound forms, the recognised precursors of 3-MCPD, and the factors influencing its formation in 5 selected coffee surrogates and 18 malts in the Czech Republic. The coffee surrogates had the free 3-MCPD level in the range of < 9.0 to 32 µg/kg while the highest amount was found in roasted barley. In malts, the free 3-MCPD levels were similarly low (< 9.0 to 45 µg/kg) being the highest in roasted malts (16-45 µg/kg). Nevertheless, the values found in either surrogates or malts, calculated after normalisation to 40% dry matter content, did not exceed the European Union limit of 20 µg/kg adopted for soy sauces and acid-HVP. The risk for consumers could arise from the bound 3-MCPD, its elevated levels having been found in both coffee surrogates and malts. In coffee surrogates, the bound 3-MCPD levels varied between 145−1184 µg/kg product; the highest level was found in roasted barley. The bound 3-MCPD levels exceeded the free 3-MCPD levels 32 to 81 times. In malts, the bound 3-MCPD levels ranged from 4.0−650 µg/kg, the highest amount having been found in roasted malts (463−650 µg/kg). The bound 3-MCPD levels exceeded the free 3-MCPD levels 0.4 to 36 times.
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Bernardo, Bianca C., Kate L. Weeks, Thawin Pongsukwechkul, Xiaoming Gao, Helen Kiriazis, Nelly Cemerlang, Esther J. H. Boey, et al. "Gene delivery of medium chain acyl-coenzyme A dehydrogenase induces physiological cardiac hypertrophy and protects against pathological remodelling." Clinical Science 132, no. 3 (February 8, 2018): 381–97. http://dx.doi.org/10.1042/cs20171269.
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We previously showed that medium chain acyl-coenzyme A dehydrogenase (MCAD, key regulator of fatty acid oxidation) is positively modulated in the heart by the cardioprotective kinase, phosphoinositide 3-kinase (PI3K(p110α)). Disturbances in cardiac metabolism are a feature of heart failure (HF) patients and targeting metabolic defects is considered a potential therapeutic approach. The specific role of MCAD in the adult heart is unknown. To examine the role of MCAD in the heart and to assess the therapeutic potential of increasing MCAD in the failing heart, we developed a gene therapy tool using recombinant adeno-associated viral vectors (rAAV) encoding MCAD. We hypothesised that increasing MCAD expression may recapitulate the cardioprotective properties of PI3K(p110α). rAAV6:MCAD or rAAV6:control was delivered to healthy adult mice and to mice with pre-existing pathological hypertrophy and cardiac dysfunction due to transverse aortic constriction (TAC). In healthy mice, rAAV6:MCAD induced physiological hypertrophy (increase in heart size, normal systolic function and increased capillary density). In response to TAC (~15 weeks), heart weight/tibia length increased by ~60% in control mice and ~45% in rAAV6:MCAD mice compared with sham. This was associated with an increase in cardiomyocyte cross-sectional area in both TAC groups which was similar. However, hypertrophy in TAC rAAV6:MCAD mice was associated with less fibrosis, a trend for increased capillary density and a more favourable molecular profile compared with TAC rAAV6:control mice. In summary, MCAD induced physiological cardiac hypertrophy in healthy adult mice and attenuated features of pathological remodelling in a cardiac disease model.
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Fukuzawa, Satoshi, Kenji Yamagata, Yuuma Hasegawa, Naomi Ishibashi-Kanno, Fumihiko Uchida, Toru Yanagawa, and Hiroki Bukawa. "Comparison of Postoperative Bleeding between Application of Polyglycolic Acid Sheet and Primary Closure in Tongue Cancer Patients with Partial Glossectomy." Dentistry Journal 8, no. 3 (August 3, 2020): 85. http://dx.doi.org/10.3390/dj8030085.
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The technique of covering a mucosal defect with fibrin glue and a polyglycolic acid sheet (MCFP) for the resection of mucosa is applied in oral cancers. The MCFP technique for partial glossectomy provides faster relief from postoperative pain and the prevention of scar contracture, unlike primary closure. However, it has a major complication of postoperative bleeding. This study sought to compare postoperative bleeding between the MCFP technique and primary closure. We designed a retrospective study with a cohort of 57 patients who underwent partial glossectomy with the MCFP technique or primary closure. Our primary predictor variable was the wound closure procedure (primary closure or the MCFP technique). The primary outcome variable was postoperative bleeding, and the other variables were patient characteristics, excision area and depth, tooth contact for the wound, and antithrombotic therapy. Statistical evaluation was performed with Pearson’s chi-squared test, Welch’s t-test, and multiple logistic regression. P < 0.05 was considered statistically significant. The MCFP technique was selected for cases with a large excision area (1433 vs. 963 mm2, P = 0.029). Total postoperative bleeding occurred in 10 of 57 patients (MCFP technique: 7 of 37 cases; primary closure: 3 of 20 cases). There was no significant difference in bleeding between the two groups (P = 0.71). Postoperative bleeding was significant in patients with antithrombotic therapy (MCFP: 40% vs. primary closure: 2%, P = 0.0024). Postoperative bleeding timing was significantly different in the MCFP technique (6.4 days) from that of primary closure (1 day; P = 0.0076). Postoperative bleeding was not associated with the MCFP technique or primary closure. However, postoperative bleeding with the MCFP technique occurred later than that with primary closure. The MCFP technique is not recommended for patients on antithrombotic therapy.
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Wang, Liyuan, Ying Ying, Zhengyan Hu, Tianjiao Wang, Xianghong Shen, and Pinggu Wu. "Simultaneous Determination of 2- and 3-MCPD Esters in Infant Formula Milk Powder by Solid-Phase Extraction and GC-MS Analysis." Journal of AOAC INTERNATIONAL 99, no. 3 (May 1, 2016): 786–91. http://dx.doi.org/10.5740/jaoacint.15-0310.
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Abstract The objective of this study was to establish a method for detecting fatty acid esters of chloropropanols [including 2-monochloropropane-1,3-diol (2-MCPD) ester and 3-monochloropropane-1,2-diol (3-MCPD) ester] in infant milk powder using isotope dilution and GC-MS. The fat fraction in infant milk powder samples was extracted and treated with sodium methylate–methanol to cleave the ester bonds of the 2- and 3-MCPD esters. The resultant 2- and 3-MCPDs in the samples were purified with matrix solid-phase liquid–liquid extraction and derivatized with heptafluorobutyryl imidazole for GC-MS analysis. Standard samples of deuterium isotope–labeled 2- and 3-MCPD palmitic acid double esters and stearic acid double esters were used as the internal standards. We also detected 2- and 3-MCPD ester contents in 88 commercial samples of infant formula milk powder using this system. The detection system we established showed a good linearity of 2- and 3-MCPD ester contents in serially diluted standard solutions within the concentration range 25−1000 μg/L, with r2 > 0.9995 and an LOD of 30 μg/kg for both of the MCPD esters. The recoveries of the two MCPD esters spiked at 25, 50, 100, and 200 μg/kg in blank infant formula milk ranged from 98.2 to 110.5%, with RSDs <4.8%, suggesting good accuracy and reliability of this method. In the 88 commercial infant formula milk powder samples, the mean content of 2-MCPD ester was 41 μg/kg (0–52 μg/kg) and that of 3-MCPD was 185 μg/kg (0–316 μg/kg). Based on these results, we estimated the exposure levels of the two MCPD esters in infants fed on formula milk, and the results indicate potential health risks of consuming formula milk products contaminated by the two MCPD esters.
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Franovic, Sreten, Noah Kuhlmann, Michael Korn, Alex Pietroski, Collin Schlosser, Eric Makhni, and Vasilios Moutzouros. "Defining MCID in patients following meniscectomy and the role of pre-operative PROMIS scores in predicting clinical improvement." Orthopaedic Journal of Sports Medicine 8, no. 7_suppl6 (July 1, 2020): 2325967120S0048. http://dx.doi.org/10.1177/2325967120s00483.
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Objectives: The Patient-Reported Outcomes Measurement Information System (PROMIS) is emerging as a valid and efficient means of collecting patient outcomes in patients with meniscal tears. Our purpose was to examine the role of pre-operative PROMIS computer adaptive test (CAT) scores in predicting post-operative PROMIS CAT scores, as well as the minimal clinically important difference (MCID) following meniscectomy. We hypothesize that pre-operative PROMIS CAT scores will directly impact both post-operative PROMIS CAT scores and likelihood of achieving MCID. Methods: Patients undergoing arthroscopic meniscectomy that completed PROMIS CAT forms for physical function (PROMIS-PF), pain interference (PROMIS-PI), and depression (PROMIS-D) were utilized. MCID was calculated according to the distribution methodology, and receiver operating characteristics (ROC) were utilized to determine if pre-operative scores were predictive of post-operative outcomes. Preoperative cutoffs were used to predict which patients would likely meet MCID, using 90% specificity. Results: A total of 135 patients met our inclusion criteria. PROMIS-PF, PROMIS-PI, and PROMIS-D improved 3 months after surgery (p<0.01). 62% of the entire cohort met MCID for PROMIS-PF, while 68% met MCID for PROMIS-PI, and 41% met MCID for PROMIS-D. Individuals with PROMIS-PF scores below 34.9 yielded an 82% probability of achieving MCID, while PROMIS-PI scores above 67.5 yielded an 86% probability of achieving MCID and a cutoff of 58.9 for PROMIS-D yielded a 60% probability of achieving MCID, with 90% specificity. Conclusions: Significant portions of patients undergoing meniscectomy achieve MCID in PROMIS-PF, PROMIS-PI, and PROMIS-D, at the 3-month time point. In particular, patients with PROMIS-PF scores of <34.9 are far more likely to achieve MCID for physical function.
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Barkay, Hadas, Robert A. Hauser, Amanda Wilhelm, Maria Wieman, Mark Forrest Gordon, and Juha-Matti Savola. "Minimal Clinically Important Difference in AIMS Score Based on CGIC and PGIC in Patients With Tardive Dyskinesia Treated With Deutetrabenazine." CNS Spectrums 26, no. 2 (April 2021): 159. http://dx.doi.org/10.1017/s1092852920002552.
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AbstractBackgroundDeutetrabenazine is FDA approved for tardive dyskinesia (TD) based on two 12-week, placebo-controlled studies evaluating safety and efficacy in patients with baseline Abnormal Involuntary Movement Scale (AIMS) score ≥6. Deutetrabenazine reduced overall AIMS scores compared with placebo in ARM-TD (–3.0 vs –1.6, P=0.019) and AIM-TD (24 mg/day, –3.2 vs –1.4, P=0.003; 36 mg/day, –3.3 vs –1.4, P=0.001). This analysis assessed Minimal Clinically Important Difference (MCID) in AIMS score in patients with TD treated with deutetrabenazine.MethodsMCID is the smallest change from baseline in AIMS score that is meaningful for patients. MCID analyses were performed based on Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors described by Hauser et al., where MCID is the difference between patients treated with deutetrabenazine who were minimally improved and patients treated with placebo who were unchanged. Additional MCID definitions were explored: difference between patients who demonstrated treatment improvement versus those who did not (Method 2); difference between patients who demonstrated treatment success versus those who did not (Method 3).Results295 patients were analyzed. Based on PGIC, the suggested MCID was –2.8. Results were similar for Method 2 (75% of patients had treatment improvement; MCID = –2.8) and Method 3 (38% of patients had treatment success; MCID = –2.6). Based on CGIC, the suggested MCID was –2.6. Results were similar for Method 2 (76% of patients had treatment improvement; MCID = –2.8) and Method 3 (41% of patients had treatment success; MCID = –3.0). Therefore, the suggested MCID for deutetrabenazine is –3.ConclusionsThe MCID for change in AIMS score based on PGIC and CGIC for deutetrabenazine was –3 regardless of the analytical method. Findings suggest an AIMS score reduction of ~3 is associated with clinically meaningful improvement in TD symptoms.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
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Watanabe, Takayuki, Takaaki Oba, Keiji Tanimoto, Tomohiro Shibata, Shinobu Kamijo, and Ken-ichi Ito. "Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer." PLOS ONE 16, no. 6 (June 8, 2021): e0252822. http://dx.doi.org/10.1371/journal.pone.0252822.
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Sequential treatment with endocrine or chemotherapy is generally used in the treatment of estrogen receptor (ER)-positive recurrent breast cancer. To date, few studies have investigated the effect of long-term endocrine therapy on the response to subsequent chemotherapy in ER-positive breast cancer. We examined whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER-positive breast cancer cells. Three ER-positive breast cancer cell lines (T47D, MCF7, BT474) and tamoxifen-resistant sublines (T47D/T, MCF7/T, BT474/T) were analyzed for sensitivity to 5-fluorouracil, paclitaxel, and doxorubicin. The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. MCF7/T cells became more sensitive to 5-fluorouracil than wild-type (wt)-MCF7 cells. In addition, the apoptosis induced by 5-fluorouracil was significantly increased in MCF7/T cells. However, no difference in sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T cells compared with their wt cells. Dihydropyrimidine dehydrogenase (DPYD) mRNA expression was significantly decreased in MCF7/T cells compared with wt-MCF7 cells. The expression of DPYD mRNA was restored with 5-azacytidine treatment in MCF7/T cells. In addition, DPYD 3′-UTR luciferase activity was significantly reduced in MCF7/T cells. These data indicated that the expression of DPYD mRNA was repressed by methylation of the DPYD promoter region and post-transcriptional regulation by miRNA in MCF7/T cells. In the mouse xenograft model, capecitabine significantly reduced the tumor volume in MCF7/T compared with MCF7. The results of this study indicate that endocrine therapy could alter the sensitivity to chemotherapeutic agents in a subset of breast cancers, and 5-fluorouracil may be effective in tamoxifen-resistant breast cancers.
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Oh, Taemin, Justin K. Scheer, Justin S. Smith, Richard Hostin, Chessie Robinson, Jeffrey L. Gum, Frank Schwab, et al. "Potential of predictive computer models for preoperative patient selection to enhance overall quality-adjusted life years gained at 2-year follow-up: a simulation in 234 patients with adult spinal deformity." Neurosurgical Focus 43, no. 6 (December 2017): E2. http://dx.doi.org/10.3171/2017.9.focus17494.
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OBJECTIVEPatients with adult spinal deformity (ASD) experience significant quality of life improvements after surgery. Treatment, however, is expensive and complication rates are high. Predictive analytics has the potential to use many variables to make accurate predictions in large data sets. A validated minimum clinically important difference (MCID) model has the potential to assist in patient selection, thereby improving outcomes and, potentially, cost-effectiveness.METHODSThe present study was a retrospective analysis of a multiinstitutional database of patients with ASD. Inclusion criteria were as follows: age ≥ 18 years, radiographic evidence of ASD, 2-year follow-up, and preoperative Oswestry Disability Index (ODI) > 15. Forty-six variables were used for model training: demographic data, radiographic parameters, surgical variables, and results on the health-related quality of life questionnaire. Patients were grouped as reaching a 2-year ODI MCID (+MCID) or not (−MCID). An ensemble of 5 different bootstrapped decision trees was constructed using the C5.0 algorithm. Internal validation was performed via 70:30 data split for training/testing. Model accuracy and area under the curve (AUC) were calculated. The mean quality-adjusted life years (QALYs) and QALYs gained at 2 years were calculated and discounted at 3.5% per year. The QALYs were compared between patients in the +MCID and –MCID groups.RESULTSA total of 234 patients met inclusion criteria (+MCID 129, −MCID 105). Sixty-nine patients (29.5%) were included for model testing. Predicted versus actual results were 50 versus 40 for +MCID and 19 versus 29 for −MCID (i.e., 10 patients were misclassified). Model accuracy was 85.5%, with 0.96 AUC. Predicted results showed that patients in the +MCID group had significantly greater 2-year mean QALYs (p = 0.0057) and QALYs gained (p = 0.0002).CONCLUSIONSA successful model with 85.5% accuracy and 0.96 AUC was constructed to predict which patients would reach ODI MCID. The patients in the +MCID group had significantly higher mean 2-year QALYs and QALYs gained. This study provides proof of concept for using predictive modeling techniques to optimize patient selection in complex spine surgery.
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Tian, Yu Dong. "Research for Experiment of Molten Carbonate Fuel Cells Generation." Applied Mechanics and Materials 193-194 (August 2012): 522–25. http://dx.doi.org/10.4028/www.scientific.net/amm.193-194.522.
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The molten carbonate fuel cell (MCFC) is an important research field of the new energy generation equipment. To aim at the problem that MCFC electrical characteristics reflect the generating performance, the electrochemical process mechanism of MCFC electrochemical reaction was analyzed firstly, then an electrical model of MCFC electrical characteristics based on the electrochemical process was advanced. Thirdly, the hot start process, and the output test of MCFC generation applied the experiment were particularly presented. Finally, the experimental results proved that it was fast and accurate.
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Zheng, Chunlei, Hui-hui Liu, Shuguang Yuan, Jiahai Zhou, and Bin Zhang. "Molecular basis of LMAN1 in coordinating LMAN1-MCFD2 cargo receptor formation and ER-to-Golgi transport of FV/FVIII." Blood 116, no. 25 (December 16, 2010): 5698–706. http://dx.doi.org/10.1182/blood-2010-04-278325.
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Abstract The LMAN1-MCFD2 (lectin, mannose binding 1/multiple coagulation factor deficiency protein 2) cargo receptor complex transports coagulation factors V (FV) and VIII (FVIII) from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC). LMAN1 (ERGIC-53) is a hexameric transmembrane protein with a carbohydrate recognition domain (CRD) on the ER luminal side. Here, we show that mutations in the first beta sheet of the CRD abolish MCFD2 binding without affecting the mannose binding, suggesting that LMAN1 interacts with MCFD2 through its N-terminal beta sheet, consistent with recently reported crystal structures of the CRD-MCFD2 complex. Mutations in the Ca2+- and sugar-binding sites of the CRD disrupt FV and FVIII interactions, without affecting MCFD2 binding. This interaction is independent of MCFD2, as LMAN1 mutants defective in MCFD2 binding can still interact with FVIII. Thus, the CRD of LMAN1 contains distinct, separable binding sites for both its partner protein (MCFD2) and the cargo proteins (FV/FVIII). Monomeric LMAN1 mutants are defective in ER exit and unable to interact with MCFD2, suggesting that the oligomerization of LMAN1 is necessary for its cargo receptor function. These results point to a central role of LMAN1 in regulating the binding in the ER and the subsequent release in the ERGIC of FV and FVIII.
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Daniel, Petr, Petr Halada, Michael Jelínek, Kamila Balušíková, and Jan Kovář. "Differentially Expressed Mitochondrial Proteins in Human MCF7 Breast Cancer Cells Resistant to Paclitaxel." International Journal of Molecular Sciences 20, no. 12 (June 19, 2019): 2986. http://dx.doi.org/10.3390/ijms20122986.
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Identification of novel proteins with changed expression in resistant cancer cells could be helpful in elucidation mechanisms involved in the development of acquired resistance to paclitaxel. In this study, we carried out a 2D-PAGE using the mitochondrial-enriched fraction from paclitaxel-resistant MCF7/PacR cells compared to original paclitaxel-sensitive MCF7 breast cancer cells. Differentially expressed proteins were identified employing mass spectrometry. We found that lysosomal cathepsin D and mitochondrial abhydrolase-domain containing protein 11 (ABHD11) had decreased expression in MCF7/PacR cells. On the other hand, mitochondrial carbamoyl-phosphate synthetase 1 (CPS1) and ATPase family AAA-domain containing protein 3A and 3B (ATAD3A, ATAD3B) were overexpressed in MCF7/PacR cells. Further, we showed that there was no difference in localization of CPS1 in MCF7 and MCF7/PacR cells. We demonstrated a significant increase in the number of CPS1 positive MCF7/PacR cells, using FACS analysis, compared to the number of CPS1 positive MCF7 cells. Silencing of CPS1 expression by specific siRNA had no significant effect on the resistance of MCF7/PacR cells to paclitaxel. To summarize, we identified several novel proteins of a mitochondrial fraction whose role in acquired resistance to paclitaxel in breast cancer cells should be further assessed.
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Mesa, A., M. Fernandez, W. Wu, G. Narasimhan, EL Greidinger, and D. K. Mills. "Can SLE classification rules be effectively applied to diagnose unclear SLE cases?" Lupus 26, no. 2 (July 11, 2016): 150–62. http://dx.doi.org/10.1177/0961203316655212.
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Objective The objective of this paper is to develop novel classification criteria to distinguish between unclear systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) cases. Methods A total of 205 variables from 111 SLE and 55 MCTD patients were evaluated to uncover unique molecular and clinical markers for each disease. Binomial logistic regressions (BLRs) were performed on currently used SLE and MCTD classification criteria sets to obtain six reduced models with power to discriminate between unclear SLE and MCTD patients that were confirmed by receiving operating characteristic (ROC) curve. Decision trees were employed to delineate novel classification rules to discriminate between unclear SLE and MCTD patients. Results SLE and MCTD patients exhibited contrasting molecular markers and clinical manifestations. Furthermore, reduced models highlighted SLE patients exhibiting prevalence of skin rashes and renal disease while MCTD cases show dominance of myositis and muscle weakness. Additionally decision tree analyses revealed a novel classification rule tailored to differentiate unclear SLE and MCTD patients (Lu-vs-M) with an overall accuracy of 88%. Conclusions Validation of our novel proposed classification rule (Lu-vs-M) includes novel contrasting characteristics (calcinosis, CPK elevated and anti-IgM reactivity for U1-70K, U1A and U1C) between SLE and MCTD patients and showed a 33% improvement in distinguishing these disorders when compared to currently used classification criteria sets. Pending additional validation, our novel classification rule is a promising method to distinguish between patients with unclear SLE and MCTD diagnosis.
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Sung, Tae Hong, and Kyung Chun Kim. "Design of Dynamic MCFC Simulation Bed for MBOP Feasibility Test of Marine Applications." Applied Mechanics and Materials 291-294 (February 2013): 589–92. http://dx.doi.org/10.4028/www.scientific.net/amm.291-294.589.
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Molten carbonate fuel cell (MCFC) is achieving relatively high output and efficiency and reaching the level of commercialization compared to other fuel cells. Recently many studies are dealt with mobile applications of MCFC to use those superlative properties. But until now, researches are dealt with steady state energy analysis and life cycle assessment analysis. The practical dynamic feasibility analysis has not been done. Here we report, dynamic MCFC model and simultaneous mechanical balance of plant (MBOP) test algorithm can be used for evaluating feasibility of MCFC marine application. We modeled four 300 kW class MCFC stacks with a dynamic form in MATLAB/ SIMULINK package. Developed simulation bed can be used to deal with overall MCFC performance evaluation and various MBOP feasibility test.
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Saitoh, Kunimasa, and Shoichiro Matsuo. "Multicore fibers for large capacity transmission." Nanophotonics 2, no. 5-6 (December 16, 2013): 441–54. http://dx.doi.org/10.1515/nanoph-2013-0037.
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AbstractWe experience Internet traffic growth of 100 times every 10 years. However, the capacity of existing standard single-mode fiber is approaching its fundamental limit regardless of significant realization of transmission technologies which allow for high spectral efficiencies. Space division multiplexing (SDM) based on multicore fibers (MCFs) has emerged as a solution to the problem of saturation of the capacity of optical transmission systems. This article presents the recent progress on the MCFs for future large capacity long-distance transmission systems. In MCFs, there is a tradeoff relationship between low crosstalk and high multiplicity, therefore the maximum number of cores and the core arrangement have to be carefully determined based on the required crosstalk level and core size. The state-of-the-art of fabricated MCFs and the transmission experiments using MCFs are reviewed. The current maximum capacity-distance product in MCF transmission is 368.2 (184.1+184.1) Pb/s/fiber km with the relative spatial efficiency of 4.7 compared with a standard single-mode fiber. In order to increase the spatial efficiency as well as the capacity-distance product further in MCFs, the possibility of heterogeneous MCFs and few-mode MCFs is also presented.
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Svejkovská, B., O. Novotný, V. Divinová, Z. Réblová, M. Doležal, and J. Velíšek. "Esters of 3-chloropropane-1,2-diol in foodstuffs." Czech Journal of Food Sciences 22, No. 5 (November 16, 2011): 190–96. http://dx.doi.org/10.17221/3423-cjfs.
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We provide here for the first time the evidence that 3-chloropropane-1,2-diol (3-MCPD) occurs in foodstuffs in its free form and also in the form of esters with higher fatty acids. These esters represent a new class of food contaminants as 3-MCPD may be released in vivoby a lipase-catalysed hydrolysis reaction. We analysed 20 samples of selected retail food products for their free and bound 3-MCPD content. All samples contained free 3-MCPD at approximately 9.6–82.7 µg/kg food (3 replications, RSD = 0.4–7.0%). The levels of bound 3-MCPD (monoesters and diesters of 3-MCPD with higher fatty acids) found in the foodstuffs analysed varied between the LOD (1.1 mg per kg of fat) and 36.8 mg/kg fat with RSD = 0.3–3.3%. Five foodstuffs of plant origin processed at high temperatures contained elevated levels of bound 3-MCPD (0.14–6.10 mg/kg). A high level of bound 3-MCPD (0.28 mg/kg) was also found in a sample of pickled fish. Some variables potentially influencing the levels of either free or bound 3-MCPD in foodstuffs were determined (pH, water, chlorides, glycerol, fat and its components) and their significance was discussed.
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Zhang, Bin, Marta Spreafico, Chunlei Zheng, Angela Yang, Petra Platzer, Michael U. Callaghan, Zekai Avci, et al. "Genotype-phenotype correlation in combined deficiency of factor V and factor VIII." Blood 111, no. 12 (June 15, 2008): 5592–600. http://dx.doi.org/10.1182/blood-2007-10-113951.
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AbstractCombined deficiency of factor V and factor VIII (F5F8D) is caused by mutations in one of 2 genes, either LMAN1 or MCFD2. Here we report the identification of mutations for 11 additional F5F8D families, including 4 novel mutations, 2 in MCFD2 and 2 in LMAN1. We show that a novel MCFD2 missense mutation identified here (D81Y) and 2 previously reported mutations (D89A and D122V) abolish MCFD2 binding to LMAN1. Measurement of platelet factor V (FV) levels in 7 F5F8D patients (4 with LMAN1 and 3 with MCFD2 mutations) demonstrated similar reductions to those observed for plasma FV. Combining the current data together with all previous published reports, we performed a genotype-phenotype analysis comparing patients with MCFD2 mutations with those with LMAN1 mutations. A previously unappreciated difference is observed between these 2 classes of patients in the distribution of plasma levels for FV and factor VIII (FVIII). Although there is considerable overlap, the mean levels of plasma FV and FVIII in patients with MCFD2 mutations are significantly lower than the corresponding levels in patients with LMAN1 mutations. No differences in distribution of factor levels are observed by sex. These data suggest that MCFD2 may play a primary role in the export of FV and FVIII from the ER, with the impact of LMAN1 mediated indirectly through its interaction with MCFD2.
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Maheshwari, Sunil Kumar, and N. Ravichandran. "Mangalore Chemicals and Fertilizers Limited: Strategic Renewal." Asian Case Research Journal 07, no. 02 (December 2003): 219–68. http://dx.doi.org/10.1142/s0218927503000409.
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This case provides a comprehensive account of the origin, foundation, growth, managerial and operational problems, labor relationship, decline in performance, change of ownership, and the initiatives taken by the new management team to revive the company. Mangalore was an initiative by Karnataka State Government in India. Originally, MCFL was conceived as a private sector organization. Eventually it was converted to a state-owned public sector undertaking. There was no accountability for the senior managers in managing the plant. Often, they had to make a trade off between their loyalty to the elected representatives and the prosperity of MCFL. Invariably, the operating officers who were usually drawn from Indian Administrative Services chose to neglect the commercial prospects of MCFL. Erratic power supply and hostile labor situation (as a consequence of inappropriate labor policies) led to frequent shut down of the plant. Consequently, the financial health of the plant deteriorated. The precarious financial position made MCFL a candidate for either closure or for sale. The Indian Government, in an attempt to revive the plant, put MCFL through two rehabilitation packages supported by its Board and its financial institutions. Eventually, MCFL was sold to UB Group in 1990. The Chairman Mr. Mallya nominated a team from UB group to manage and revive MCFL. As of 2002, MCFL is a profit-generating organization. The management has to decide, how MCFL should grow from now onwards.
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Doganay Erdogan, Beyza, Ying Ying Leung, Christoph Pohl, Alan Tennant, and Philip G. Conaghan. "Minimal Clinically Important Difference as Applied in Rheumatology: An OMERACT Rasch Working Group Systematic Review and Critique." Journal of Rheumatology 43, no. 1 (June 1, 2015): 194–202. http://dx.doi.org/10.3899/jrheum.141150.
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Objective.We aimed to evaluate how minimal (clinically) important differences (MCID/MID) were calculated in rheumatology in the past 2 decades and demonstrate how the calculation is compromised by the lack of interval scaling.Methods.We conducted a systematic literature review on articles reporting MCID calculation in osteoarthritis (OA) and rheumatoid arthritis (RA) from January 1, 1989, to May 9, 2014. We evaluated the methods of MCID calculation and recorded the ranges of MCID for common patient-reported outcome measures (PROM). Taking data from the Health Assessment Questionnaire (HAQ), we showed the effects of performing mathematical calculations on ordinal data.Results.A total of 330 abstracts were reviewed and 123 articles chosen for full text review. Thirty-six (19 OA, 16 RA and 1 OA-RA) articles were included in the final evaluation. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most frequently reported PROM with relevant calculations in OA, and the HAQ in RA. Sixteen articles used anchor-based methods alone for calculation of MCID, and 1 article used distribution-based methods alone. Nineteen articles used both anchor and distribution-based methods. Only 1 article calculated MCID using an interval scale. Wide ranges in MCID for the WOMAC in OA and HAQ in RA were noted. Ordinal-based derivations of MCID are shown to understate true change at the margins, and overstate change in the mid-range of a scale.Conclusion.The anchor-based method is commonly used in the calculation of MCID. However, the lack of interval scaling is shown to compromise validity of MCID calculation.
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Divinová, V., B. Svejkovská, M. Doležal, and J. Velíšek. "Determination of free and bound 3-chloropropane-1,2-diol by gas chromatography with mass spectrometric detection using deuterated 3-chloropropane-1,2-diol as internal standard." Czech Journal of Food Sciences 22, No. 5 (November 16, 2011): 182–89. http://dx.doi.org/10.17221/3422-cjfs.
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An improved routine, simple and sensitive method is presented for the determination of free and bound 3-chloropropane-1,2-diol (3-MCPD) in different foods using capillary gas chromatography with mass spectrometric detection and deuterated 3-MCPD as internal standard. The optimised method was linear within the working calibration standard concentrations in the range of 0.009–1.3 mg 3-MCPD per 1 kg of sample. The LOD and LOQ were 0.003 µg/kg and 0.009 µg/kg, respectively. Validation of the method was carried out by analysing standards of<br /> 3-MCPD, acid-HVP, roasted coffee samples, and the same samples spiked with 3-MCPD. Repeatability (expressed as RSD) of the method was in the range 1.0–4.2%, the average spike recoveries were 99.1–99.5% (RSD = 0.8–1.4%), respectively. 3-MCPD bound in esters with higher fatty acids was isolated as fat, the isolated fat was subjected to methanolysis and 3-MCPD generated was quantified using the same method. The LOD and LOQ were determined to be 1.1 mg/kg of lipids and 3.3 mg/kg of lipids, respectively. Using the optimised method, 20 samples of retail food products were analysed for their free and bound 3-MCPD. All samples contained free 3-MCPD at 9.6–83 µg/kg (RSD = 0.4–7.0%). The level of the bound 3-MCPD varied between the LOD and 2.4 mg/kg with RSD = 0.3–2.4%.
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Ostermeyer, Ute, Sybille Merkle, Horst Karl, and Jan Fritsche. "Free and bound MCPD and glycidyl esters in smoked and thermally treated fishery products of the German market." European Food Research and Technology 247, no. 7 (April 16, 2021): 1757–69. http://dx.doi.org/10.1007/s00217-021-03746-6.
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AbstractTo provide a comprehensive overview of the amounts of unesterified and bound 2- and 3-monochloropropanediol (MCPD) and glycidyl esters (G–E) in processed fishery products sold in Germany, an analysis of various frequently consumed products was conducted. In total, 258 commercial samples of breaded and pre-fried fishery products (e.g., frozen fish fingers), fried fish products (e.g., products in marinade), canned fish, smoked fish and some smoked spice preparations were examined. In addition, the effect of different kitchen preparation methods (e.g., baking, frying and roasting) on the MCPD and G–E amounts of fish fingers was studied. The mentioned process contaminants, MCPD and G-E, were quantifiable in the majority of the samples. Although pre-fried and fried fishery products predominantly contained MCPD esters (MCPD-E), mainly free MCPD was found in smoked fish. Compared with other types of smoke generation, hot smoked fish prepared in traditional Altona smoking kilns contained, on average, the highest 3-MCPD contents (range: 12–246 µg/kg). The amounts of bound MCPD in the fried fish products (range for 3-MCPD-E: < LOQ-808 µg/kg) were not significantly different from the amounts in the investigated pre-fried fish samples (range for 3-MCPD-E: < LOQ-792 µg/kg). However, they differ significantly from the amounts in unfried products (< LOQ). After preparation in the kitchen, the contents in the ready-to-eat fish fingers depend primarily on the initial contaminant amounts of the frozen product and/or the frying oil, respectively.
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Gunashekar, S., M. Prakash, R. W. Minz, A. Sharma, S. Sharma, and V. Dhir. "Comparison of articular manifestations of mixed connective tissue disease and systemic lupus erythematosus on clinical examination and musculoskeletal ultrasound." Lupus 27, no. 13 (October 10, 2018): 2086–92. http://dx.doi.org/10.1177/0961203318804891.
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Background Polyarthritis is common to both mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE). Apart from being erosive and deforming in the former, we speculated that it was more common and the extent of joints involved would be higher in MCTD. Methods This was a cross-sectional study that included patients with MCTD aged 18–75 years fulfilling the Kasukawa criteria. An equal number of patients with SLE matched for disease duration and gender were included. Clinical manifestations were compared between patients with MCTD and with SLE. Examination of joints was done for the presence of tenderness or swelling and deformity. Musculoskeletal ultrasound was done on the non-dominant hand for detection of synovitis and tenosynovitis and radiographs of the hands were obtained. The use of methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis was noted. Statistical tests used were non-parametric. Results Forty patients with MCTD and forty patients with SLE were included in this study, with patients being slightly older in MCTD than SLE (36 ± 10.2, 31.8 ± 13.3 years, p = 0.01). There were no significant differences in disease duration (4.7 ± 3.1, 3.7 ± 2.3, p = 0.1) or gender (females = 38, 38). Nearly one-half of patients with MCTD had at least one swollen joint compared with only 15% of patients with SLE. Median (95% confidence interval) tender joint count (5 (4.8–10.4), 0 (1.3–7.2), p = 0.01) and swollen joint count (0 (0.9–2.6), 0 (0–1.2), p = 0.002) was significantly higher in patients with MCTD compared with SLE. More patients with MCTD than SLE had tender or swollen proximal interphalangeal joints (12, 4, p = 0.025). More patients with MCTD than SLE had received methotrexate (8,2, p = 0.04) and NSAIDs (39, 32, p = 0.03) for arthritis. There was no difference in the number of patients with MCTD or SLE who had evidence of synovitis or tenosynovitis on ultrasound. There was no difference in erosive disease on hand radiographs, but acro-osteolysis was higher among MCTD patients. Conclusions A higher proportion of patients with MCTD had at least one swollen and tender joint as compared with patients with SLE, as well as higher use of methotrexate and NSAIDs. However, there was no difference in ultrasound detected synovitis or tenosynovitis.
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Birchmeier, C., D. Birnbaum, G. Waitches, O. Fasano, and M. Wigler. "Characterization of an activated human ros gene." Molecular and Cellular Biology 6, no. 9 (September 1986): 3109–16. http://dx.doi.org/10.1128/mcb.6.9.3109.
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A human oncogene, mcf3, previously detected by a combination of DNA-mediated gene transfer and a tumorigenicity assay, derives from a human homology of the avian v-ros oncogene. Both v-ros and mcf3 can encode a protein with homology to tyrosine-specific protein kinases, and both mcf3 and v-ros encode a potential transmembrane domain N terminal to the kinase domain. mcf3 probably arose during gene transfer from a normal human ros gene by the loss of a putative extracellular domain. There do not appear to be any other gross rearrangements in the structure of mcf3.
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Tian, Yu Dong. "Analysis for Modeling of Molten Carbonate Fuel Cells Material Characteristics." Advanced Materials Research 568 (September 2012): 344–47. http://dx.doi.org/10.4028/www.scientific.net/amr.568.344.
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The molten carbonate fuel cell (MCFC) is a difficulty in the research field of high-temperature fuel cells at present, and its strict hot start process and running status influence the material performance and life of the cell greatly. To deal with the problem, the MCFC mathematical modeling was analyzed firstly. Then a model of MCFC process based on material characteristics was advanced. Thirdly, the MCFC modeling structure, algorithm, and simulation applied the electrochemical processes were particularly presented. Finally, the results proved that it was fast and accurate, and provided the suitable model of MCFC system control at the view of application.
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Birchmeier, C., D. Birnbaum, G. Waitches, O. Fasano, and M. Wigler. "Characterization of an activated human ros gene." Molecular and Cellular Biology 6, no. 9 (September 1986): 3109–16. http://dx.doi.org/10.1128/mcb.6.9.3109-3116.1986.
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A human oncogene, mcf3, previously detected by a combination of DNA-mediated gene transfer and a tumorigenicity assay, derives from a human homology of the avian v-ros oncogene. Both v-ros and mcf3 can encode a protein with homology to tyrosine-specific protein kinases, and both mcf3 and v-ros encode a potential transmembrane domain N terminal to the kinase domain. mcf3 probably arose during gene transfer from a normal human ros gene by the loss of a putative extracellular domain. There do not appear to be any other gross rearrangements in the structure of mcf3.
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Kuhlmann, Jan. "2-Monochloropropanediol (2-MCPD), 3-Monochloropropanediol (3-MCPD), and Glycidol in Infant and Adult/Pediatric Nutritional Formula: Single-Laboratory Validation, First Action 2018.12." Journal of AOAC INTERNATIONAL 102, no. 4 (July 1, 2019): 1205–20. http://dx.doi.org/10.5740/jaoacint.19-0026.
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Abstract Background: Fatty acid esters of glycidol, 2-Monochloropropanediol (MCPD), and 3-MCPD are heat-induced foodborne processing contaminants with possible adverse health effects. These compounds occur frequently in refined edible oils. Consequently, glycidyl esters and 2- and 3-MCPD esters might also be present in foods that contain refined edible oils. Objective: This manuscript describes the single-laboratory validation of an analytical method for the quantitative determination of glycidol, 2-MCPD, and 3-MCPD present as fatty acid esters or as free 2- or 3-MCPD in infant and adult/pediatric nutritional formula. Methods: Technically, the presented method is based on the combination of a Heat-Ultrasound Pressure-supported Solvent Extraction and a GC–MS determination of glycidol, 2-MCPD, and 3-MCPD. From a chemical perspective, the method includes an alkaline catalyzed transesterification, conversion of the unstable glycidol into monobromopropanediol, and the parallel derivatization of all analytes with phenylboronic acid. Results: Validation results showed that method linearity for all analytes in powdered and liquid infant formula ranged from 0.9981 to 0.9999 (n = 18). Repeatability relative standard deviation values for concentration levels between 1.3 μg/kg and 331 μg/kg were in the range of 1 to 12%. Relative recoveries were found to be between 93 and 107%. The analytes were quantifiable down to 5–10 μg/kg in powdered samples and 1–2 μg/kg in liquid samples. Conclusions: The reported results met actual AOAC Standard Method Performance Requirements. Highlights: In terms of consumer protection, the presented method is a novel approach for the sensitive and accurate determination of glycidol, 2-MCPD, and 3-MCPD in infant formula and related foodstuffs.
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Reddy, Vishruth K., Scott L. Parker, Samit A. Patrawala, Dennis T. Lockney, Pei-Fang Su, and Robert A. Mericle. "Microvascular Decompression for Classic Trigeminal Neuralgia." Neurosurgery 72, no. 5 (January 16, 2013): 749–54. http://dx.doi.org/10.1227/neu.0b013e318286fad2.
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Abstract BACKGROUND: Outcomes studies use patient-reported outcome (PRO) measurements to assess treatment effectiveness, but can lack direct clinical meaning. Minimum clinically important difference (MCID) calculation provides a point estimate of the critical threshold needed to achieve clinically relevant treatment effectiveness. MCID remains uninvestigated for microvascular decompression (MVD), a common surgical procedure for trigeminal neuralgia. OBJECTIVE: We aimed to determine MCID for the most commonly used PRO measures of pain after MVD: Visual Analog Scale (VAS) and Barrow Neurological Institute Pain Scale (BNI-PS). METHODS: Sixty consecutive patients with classic trigeminal neuralgia who decided to undergo MVD by a single surgeon were prospectively assessed with VAS and BNI-PS preoperatively and 2 years postoperatively. Three anchors were used to assign each patient's outcome. We then used 3 well-established, anchor-based methods to calculate MCID. RESULTS: Patients experienced significant improvement in both VAS (9.9 vs 2.0, P < .001) and BNI-PS (5.0 vs 1.9, P < .001) after MVD. The area under the receiver-operating characteristic curve was greater for BNI-PS than for VAS for all 3 anchors, indicating that BNI-PS is probably better suited for calculating MCID. The 3 MCID calculation methods generated a range of MCID values for each of the PROs (VAS: 1.40-8.87, BNI-PS: 0.95-3.26). CONCLUSION: MVD-specific MCID is highly variable based on calculation technique. Some of these calculations appear to either overestimate or underestimate the patients' preoperative expectations. When the different MCID methods are averaged, the results are clinically appropriate and consistent with preoperative expectations. The average MCID for VAS is 6.25 and for BNI-PS is 2.44.
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Novak, Elizabeth M., and Sheila M. Innis. "Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism." American Journal of Physiology-Endocrinology and Metabolism 301, no. 5 (November 2011): E807—E817. http://dx.doi.org/10.1152/ajpendo.00225.2011.
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Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver. Rats were fed a low-fat diet or one of six higher-fat diets, varying in 16:0, 18:1n-9, 18:2n-6, 18:3n-3, and long-chain (LC) n-3 fatty acids. Higher maternal dietary 18:2n-6 or 18:3n-3 did not influence milk MCFA, but lower maternal plasma triglycerides, due to either a low-fat or a high-fat high-LC n-3 diet led to higher milk MCFA. MCFA levels were inversely associated with 18:1n-9, 18:2n-6, and 18:3n-3 in human milk, likely reflecting the association between dietary total fat and unsaturated fatty acids. High LC n-3 fatty acid in rat milk was associated with lower hepatic Pklr, Acly, Fasn, and Scd1 and higher Hmgcs2 in the milk-fed rat neonate, with no effect of milk 18:1n-9, 18:2n-6, or MCFA. These studies show that the dietary fatty acid composition does not impact MCFA secretion in milk, but the fatty acid composition of milk, particularly the LC n-3 fatty acid, is relevant to hepatic metabolic regulation in the milk-fed neonate.
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Yang, Chen, Kangjie Deng, Hangxing He, Haochuang Wu, Kai Yao, and Yuanzhe Fan. "Real-Time Interface Model Investigation for MCFC-MGT HILS Hybrid Power System." Energies 12, no. 11 (June 8, 2019): 2192. http://dx.doi.org/10.3390/en12112192.
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The research on the control strategy and dynamic characteristics of the Molten Carbonate Fuel Cell-Micro Gas Turbine (MCFC-MGT) hybrid power system has received much attention. The use of the Hardware-In-the-Loop Simulation (HILS) method to study the MCFC-MGT hybrid power system, where the MCFC is the model subsystem and the MGT is the physical subsystem, is an effective means to save development cost and time. The difficulty with developing the MCFC-MGT HILS system is the transfer of the mass, energy, and momentum between the physical subsystem and the model subsystem. Hence, a new Simulation–Stimulation (Sim–Stim) interface model of the MCFC-MGT HILS hybrid power system to achieve a consistent mass, energy, and momentum with the prototype system of the MCFC-MGT hybrid power system is proposed. In order to validate the Sim–Stim interface model before application in an actual system, both a real-time model of the MCFC-MGT hybrid power system and the MCFC-MGT HILS hybrid power system based on the Sim–Stim interface model were developed in the Advanced PROcess Simulation (APROS) platform. The step-up and step-down of the current density, which were strict for the Sim–Stim interface model, were studied in these two models. The results demonstrated that the Sim–Stim interface model developed for the MCFC-MGT HILS hybrid power system is rapid and reasonable.
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Sugino, T., A. Tateno, G. Ueno, K. Kawashima, T. Okimura, H. Hirabayashi, A. Suzuki, et al. "Effects of calcium salts of medium-chain fatty acids on plasma metabolite and hormone concentrations in early lactating dairy cows." Animal Production Science 54, no. 10 (2014): 1699. http://dx.doi.org/10.1071/an14233.
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To elucidate the effects of medium-chain fatty acids (MCFA) on milk production and plasma metabolite and hormone concentrations in early lactating dairy cows, 10 multiparous Holstein dairy cows were randomly assigned to two dietary treatment groups after parturition. One group was fed a diet supplemented with calcium salts of MCFA (MCFA-Ca) for 8 weeks after parturition, while the other group was fed the same diet without the supplement (control). MCFA-Ca, containing 60% caprylic acid and 40% capric acid, was added to a total mixed ration (TMR) at 1.5% of the dietary dry matter (DM). Cows were offered the TMR ad libitum. DM intake, daily gain in bodyweight, milk yield, milk fat content and milk protein content did not differ between the two treatment groups. The MCFA-Ca diet decreased plasma glucose and triglyceride concentrations (P < 0.05), while plasma concentrations of total and free cholesterols tended to increase (P < 0.10). Plasma ghrelin was maintained at a higher concentration (P < 0.05) in cows fed the MCFA-Ca diet than in the control group. Relative to the control diet, the MCFA-Ca diet decreased plasma insulin concentration (P < 0.05) and numerically increased plasma glucagon concentration, resulting in a lower insulin : glucagon ratio (P < 0.05). In conclusion, plasma metabolite and hormone concentrations were affected by the MCFA-Ca diet, suggesting that MCFA-Ca supplementation may change endocrine functions and nutrient metabolism in early lactating cows, ultimately resulting in an enhanced catabolic state.
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Gunnarsson, Ragnar, Øyvind Molberg, Inge-Margrethe Gilboe, and Jan Tore Gran. "The prevalence and incidence of mixed connective tissue disease: a national multicentre survey of Norwegian patients." Annals of the Rheumatic Diseases 70, no. 6 (March 11, 2011): 1047–51. http://dx.doi.org/10.1136/ard.2010.143792.
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ObjectivesMixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown aetiology. As the epidemiology of the disease is largely unknown, the authors performed a nationwide cross-sectional retrospective study to assess the prevalence and incidence of MCTD in Norway.MethodsEvery adult patient (≥18 years) with MCTD seen at one of the departments of rheumatology was reviewed for inclusion. Only patients who satisfied the following four criteria were included: clinical diagnosis of MCTD verified by a rheumatologist; positive serum anti-ribonucleoprotein antibody test; fulfilment of at least one of three of following criteria sets: the modified Sharp's criteria, the criteria of Alarcón-Segovia and Villareal and those of Kasukawa; and exclusion of other connective tissue diseases.ResultsThe four inclusion criteria were fulfilled by 147 adult Caucasian patients. The female to male ratio was 3.3 and the mean age at diagnosis of adult-onset MCTD was 37.9 years (95% CI 35.3 to 40.4 years). At the end of 2008, the point prevalence of living adult MCTD patients in Norway was 3.8 (95% CI 3.2 to 4.4) per 100 000 adults. The incidence of adult-onset MCTD in Norway during the period from 1996 to 2005 was 2.1 (95% CI 1.7 to 2.5) per million per year.ConclusionsMCTD has a female predominance and the incidence and prevalence of MCTD is low, and lower than reported figures for polymyositis, dermatomyositis, systemic sclerosis and systemic lupus erythematosus. The prevalence estimates were similar across the three criteria sets of MCTD.
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Sedaghat, Ahmad R. "Understanding the Minimal Clinically Important Difference (MCID) of Patient-Reported Outcome Measures." Otolaryngology–Head and Neck Surgery 161, no. 4 (June 4, 2019): 551–60. http://dx.doi.org/10.1177/0194599819852604.
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ObjectiveThe minimal clinically important difference (MCID) of a patient-reported outcome measure (PROM) represents a threshold value of change in PROM score deemed to have an implication in clinical management. The MCID is frequently used to interpret the significance of results from clinical studies that use PROMs. However, an understanding of the many caveats of the MCID, as well as its strengths and limitations, is necessary. The objective of this article is to provide a review of the calculation, interpretation, and caveats of MCID.Data SourcesMEDLINE and PubMed Central.Review MethodsLiterature search—including primary studies, review articles, and consensus statements—pertinent to the objectives of this review using PubMed.ConclusionsThe MCID of a PROM may vary depending on the patients and clinical context in which the PROM is given. The primary approaches for calculating MCID are distribution-based and anchor-based methods. Each methodology has strengths and limitations, and the ideal determination of a PROM MCID includes synthesis of results from both approaches. The MCID of a PROM is also not perfect in detecting patients experiencing a clinically important improvement, and this is reflected in its accuracy (eg, sensitivity and specificity).Implications for PracticeInterpretation or application of MCID requires consideration of all caveats underlying the MCID, including the patients in whom it was derived, the limitations of the methodologies used to calculate it, and its accuracy for identifying patients who have experienced clinically significant improvement.
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Lynch, Barry S., Douglas W. Bryant, Graham J. Hook, Earle R. Nestmann, and Ian C. Munro. "Carcinogenicity of Monochloro-1,2-Propanediol (α-Chlorohydrin, 3-MCPD)." International Journal of Toxicology 17, no. 1 (January 1998): 47–76. http://dx.doi.org/10.1080/109158198226756.
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3-Monochloro-1,2-propanediol (3-MCPD) is a by-product found in trace amounts, generally less than 1 mg/kg (<1 ppm), in hydrolyzed vegetable protein produced through acid hydrolysis. In a chronic study with F344 rats, high doses of 3-MCPD produced benign renal tumors in both sexes and Leydig-cell and mammary tumors in males. 3-MCPD is genotoxic in vitro, but there is no evidence of genotoxicity in vivo. There is some question about the mechanism responsible for the carcinogenicity of 3-MCPD in certain species. Here we present a critical review of the toxicological, metabolic, and mechanistic data on 3-MCPD. On the basis of this review, the tumors reported in F344 rats are concluded to have developed as a result of nongenotoxic mechanisms and are considered not to be relevant to humans exposed to trace amounts of 3-MCPD. This conclusion was based on the lack of carcinogenicity of 3-MCPD in mice or Sprague-Dawley rats; the benign nature of the tumors involved; the dependence of the Leydig-cell and mammary tumors on species-and strain-dependent mechanisms involving chronic changes in hormone balance; the association of the renal tumors with chronic nephropathy and nephrotoxicity; and differences between bacterial and mammalian systems in the metabolism of 3-MCPD that likely account for its genotoxic activity in certain in vitro test systems. At trace levels in foods, 3 MCPD is considered not to pose a carcinogenic risk to humans.
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Casco-Ojeda, Rubi, Yolanda Flores-Peña, Monserrat Morales-Alducin, Juana Mercedes Gutiérrez-Valverde, Hermelinda Avila-Alpirez, and Corina Mariela Alba-Alba. "Mindful Parenting, Maternal Child Feeding Style and Prescholer's Body Mass Index." Current Developments in Nutrition 5, Supplement_2 (June 2021): 966. http://dx.doi.org/10.1093/cdn/nzab051_010.
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Abstract Objectives To compare the dimensions and total score of Mindful Parenting (MP) according to the Maternal Child-Feeding Style (MCFS), 2) To identify the MCFS with the highest BMI average score and to verify if there are significant differences. Methods This study was of the descriptive and correlational type. The sample was determined for a multiple linear regression model with eight variables, significance of 0.5, test power of 90%, and effect size of .07. Participated, 334 dyads (mothers and her preschool child). The child attended 10 publish kindergartens in Monterrey, Nuevo Leon, México. Mothers answered the Interpersonal Mindfulness in Parenting Scale and the Caregiver's Feeding Styles Questionnaire. The preschooler's weight and height were measured. Descriptive and inferential statistics were applied. Results The MP dimension with the highest average was Emotional Awareness of the Self and the Child (Mean = 71.14, SD = 14.90), the average of the total score of MP was 69.48 (SD = 10.60). The indulgent MCFS was the most frequent 33.7% (n = 116). The authoritative MCFS presented the highest score of MP (H = 27.068, P = .001). The indulgent MCFS presented the highest average range of child's BMI (121.70) when compared against the authoritarian MCFS (102.62), a significant difference was identified (U = 5197.00, P < .05). Conclusions The authoritative MCFS had highest score of MP. Moreover the authoritative MCFS had been related to health child's BMI. It is recommended to design interventions to promote MP and authoritative MCFS. Funding Sources …
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Nguyễn Thành, Duy, Tâm Lê Thanh, Kiệt Lý Tuấn, Tấn Phú Minh, Hùng Nguyễn Quốc, and Hải Chu Vân. "Xác định đồng thời nhóm Acid béo 2-Chloro-1,3-Propandiol (2-MCPD), 3-Chloro-1,2-propandiol (3-MCPD) và glycidol trong dầu thực vật bằng sắc ký khí ghép khối phổ GC-MS/MS." Heavy metals and arsenic concentrations in water, agricultural soil, and rice in Ngan Son district, Bac Kan province, Vietnam 2, no. 3 (September 27, 2019): 67–73. http://dx.doi.org/10.47866/2615-9252/vjfc.715.
Full textAbstract:
Trong những năm gần đây, một số chất gây ô nhiễm thực phẩm như 3-chloro-1,2-propanediol (3-MCPD) và ester acid béo 3-MCPD đã được tìm thấy trong nhiều loại thực phẩm. Trong đó, một lượng đáng kể các hợp chất acid béo 2-chloro-1,3-propanediol (2-MCPD) đã được phát hiện trong các loại dầu tinh chế. Kỹ thuật sắc ký khí ghép khối phổ được sử dụng để định lượng các acid béo dạng ester bao gồm 2-Chloro-1,3-propandiol (2-MCPD), 3-Chloro-1,2-propandiol (3-MCPD) và glycidol trong dầu. Mẫu được chuẩn bị bằng cách sử dụng các nội chuẩn bao gồm 3-MCPD-ester-d5 (rac 1,2-bis-palmitoyl- 3-chloropropanediol-d5), 2-MCPD-ester-d5 (1,3-Distearoyl-2-chloropropanediol-d5) và Glycidyl sterate-d5, tiến hành 2 bước ủ mẫu bằng dung dịch NaBr/H2SO4 và H2SO4/MeOH, trích ly với dung môi ethyl acetate, n-hexan để chuyển đổi Glycidyl ester thành MCPD và glycidol dạng tự do trong mẫu trước khi sử dụng dẫn xuất phenylboronic acid. Giới hạn định lượng là 0,1 mg/kg tương ứng, hiệu suất thu hồi ở nồng độ 0,1 mg/kg khoảng 80 - 120% với độ lặp lại và độ tái lập thấp hơn 10%.