575 research outputs found
Gas phase studies of hypoxanthine:
No full textHypoxanthine is not only a naturally occurring nucleobase in tRNA but also a damaged one in DNA arising from oxidative deamination of adenine. This thesis describes studies of the intrinsic reactivity of hypoxanthine as a free base and the stability of DNA duplexes containing hypoxanthine in the gas phase versus in solution by calculation and mass spectrometry methods.
Firstly, the free base of hypoxanthine is studied as a damaged nucleobase. Hypoxanthine is one of the damaged nucleobases that can be excised by Alkyladenine DNA glycosylase (AAG) in humans. To understand the intrinsic properties of hypoxanthine, we examined the gas phase acidity and proton affinity using quantum mechanical calculations and gas-phase mass spectrometric experimental methods. We find that the N9-H of hypoxanthine is more acidic than that of adenine and guanine, pointing to a way by which AAG may discriminate damaged bases from normal bases. We hypothesize that AAG may cleave certain damaged nucleobases as anions and the active site may take advantage of a nonpolar environment to favor deprotonated hypoxanthine as a better leaving group than adenine and guanine. The acidities of AAG substrates have been compared with those of normal bases by calculations and Cooks kinetics method. In addition, the acidity differences between damaged and normal bases are enhanced in the gas phase when we compare them with the acidities in solution. These results support our hypothesis.
Secondly, to understand the effect of hypoxanthine on DNA stability, we study a series of 9-mer DNA duplexes with the sequence 5'-d(GGTTXTTGG)-3'/3'-d(CCAAYAACC)-5', where the central base X or Y = adenine (A), guanine (G), thymine (T), cytosine (C) and hypoxanthine (H). Comparison of the duplex stability in the gas phase versus in solution indicates that hypoxanthine has much less of a destabilizing effect in the gas phase versus in solution, relative to the normal complementary duplexes. The biological implications of these results are discussed in the context of hypoxanthine both as a universal base and as a damaged base.Ph.D.Includes bibliographical referencesby Xuejun Su
LED-Based Luminaire Color Shift Acceleration and Prediction
No full textColor stability is of major concern for LED-based products. Currently, much effort is done on lumen maintenance, and for color shift, no agreed method currently exists, be it from testing or from prediction side. To investigate the physics of color shift, we present experiments of each individual part failure of each individual part that are present in LED-based products. In order to develop a color shift prediction method, it is imperative to investigate the color shift contribution by each individual part. We present a new method to predict color shift on a system level, which we named the view factor approach. We compare this prediction method with experiments on luminaire level to conclude that we have taken satisfactory first steps in the field of color shift predictions for LED-based systems.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic Components, Technology and Material
Reliability Prediction of Integrated LED Lamps with Electrolytic Capacitor-Less LED Drivers
No full textThis chapter investigates the reliability of the integrated LED lamps with electrolytic capacitor-less LED drivers. Firstly, the impact of the interaction between the degradations of the LED light source and the driver on the lumen depreciation is studied. The electronic-thermal simulation was carried out to obtain the history of temperatures of LED and driver, the driver’s output current, and the luminous flux considering the variations of temperature and current throughout the operation life. It is found that the ultimate lamp’s lifetime is significantly less than the individual lifetimes of the preselected LED and driver. It is concluded that it is necessary to apply the electronic-thermal simulations to predict the lifetime of LED lamps when driver’s lifetime is comparable to the LED’s lifetime. Secondly, this chapter focuses on predicting the catastrophic failure of an electrolytic capacitor-free LED driver during the lumen depreciation process. Electronic-thermal simulations are utilized to obtain the lamp’s dynamic history of temperature and electrical current for two distinct modes: constant current mode (CCM) and the constant optical output (CLO) mode, respectively. A fault tree method is applied to calculate the system’s MTTF, and the LED’s lifetime also is calculated. The CLO mode increases the LED’s current exponentially to maintain the constant light output. As a result, junction temperatures of LEDs, MOSFET, and diode rise significantly, leading a shorter lifetime and MTTF. Compare with the current of the MOSFET, the increased junction temperature has larger effects on the failure rate. The MOSFET contributes more to the driver’s failure rate than the diode. For the CCM mode, junction temperatures increase slightly and have a little shorter lifetime and MTTF.Electronic Components, Technology and Material
Thermodynamically controlled synthesis of covalent nanocapsules
No full textChapter 1 gives a general overview about molecular container compounds.
In Chapter 2, a new method for the room temperature stabilization of fluorophenoxycarbene is described. In this approach, photolysis of incarcerated fluorophenoxydiazirine generated fluorophenoxycarbene in the inner phase of a hemicarcerand, which protected the carbene from dimerization. As a result of its high stability, 1H, 13C and 19F NMR spectroscopic properties of this carbene were obtained at room temperature. The reaction of the incarcerated carbene with bulk phase water and its inner phase conformation were explored.
The synthesis of covalent nanocapsules is challenging and current multi-step syntheses give nanocapsules only in relatively low overall yield. In Chapter 3 and 4, a dynamic covalent chemistry approach has been developed to prepare nanocapsules in high yield in a single step from multiple small building blocks. Nanometersized molecular capsules of this type have potential for applications in drug, pesticide and RNA delivery and as nanoreactors. In Chapter 3, three different nanocapsules, whose structures resemble a distorted tetrahedron, octahedron, or square antiprism, are described. These capsules are prepared by condensation reactions between 4, 6, and 8 tetraformyl cavitands 40 and 8, 12, and 16 ethylenediamines 43, respectively. They have cavity volumes of 450-3000 Å3. In Chapter 4, synthesis of a series of distorted tetrahedral nanocapsules through reaction of 40 with rigid linear diamines 48a-c is described. These capsules form 1:1 and 1:2 complexes with tetraalkylammonium salts of appropriate size, in which the tetraalkylammonium guests are encapsulated in the cavity of the nanocapsule.
In Chapter 5, dynamic combinatorial libraries (DCL) of polyimino nanocapsules are constructed by reacting 40 with a combination of 2 or 3 different diamine linkers 41, 44d, 48a, and 48b.
In Chapter 6, the syntheses of water-soluble nanocapsules are described. They are prepared by attaching hydrophilic functional groups and charged groups to the nanocapsules. Binding studies in water revealed that these nanocapsules encapsulate negatively charged organic compounds. The water soluble nanocapsules possess large portals and a roomy inner cavity and potentially may serve as devices for drug delivery and controlled release applications.Ph.D.Includes bibliographical references
Abstract 4750: Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical cancer
No full textAbstract
Background and Purpose: To determine significant factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node (PALN) metastasis treated with concurrent chemoradiation with a specific focus on radiation dose to total bone marrow (BMTOT) and active bone marrow (BMACT). To create a nomogram using significant factors to predict HT in these patients.
Material and Methods: 38 Patients with cervical cancer and PALN metastasis who underwent 18F-FDG-PET / CT before treatment with extended field radiation therapy (EFRT) and concurrent cisplatin were analyzed. BMACT was defined as the region within BMTOT with a standardized uptake value (SUV) greater than or equal to the mean for the individual. Blood counts were collected weekly from the beginning of radiation treatment to the end of radiation treatment. HT was graded based on the guidelines set by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
Results: 19 patients (50%) had Grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Patients who were obese (n=12) were less likely to get HT3+ compared to patients who were not obese (p=0.03) despite getting the same weight related dose of chemotherapy. Volume of BMTOT receiving 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 78.56% (p=0.01), 47.14% (p=0.00), and 20.36% (p=0.01) respectively. Volume of BMACT receiving 10 Gy, 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 95.50% (p=0.03), 80.52% (p=0.05), 59.64% (p=0.03), and 31.74% (p=0.01) respectively. Through logistic regression, the probability of developing HT3+ is given by the equation: Prob(HT3+) = 1 / (1 + exp(7.34 + 0.22*BMI - 0.44*Mean Dose to BMTOT)). Patients who had HT3+ received an average of 4 cycles of chemotherapy and 62 days of treatment time, significantly different than the 4.74 chemotherapy cycles and 53 days of treatment in patients without HT3+ (p=0.05, 0.00 respectively).
Conclusions: Both higher patient BMI and bone marrow irradiation were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients. Radiation parameters have been identified for cervical cancer patients with PALN involvement receiving EFRT concurrently with chemotherapy. Bone marrow sparing approaches for EFRT need to be addressed to improve patient care.
Citation Format: Kevin Yan, Ezequiel Ramirez, Xuejun Gu, Kevin Albuquerque. Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4750. doi:10.1158/1538-7445.AM2017-4750</jats:p
Masking Enhances Accuracy of Bladder Deformation in Multi-Fraction Adaptive Brachytherapy as a First Step Toward Composite Dose Estimation
Get PDFThe 52nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, February 4, 2014, 3-6 p.m., D1.502)BACKGROUND: GEC-ESTRO guidelines for cervix HDR brachytherapy advocate measurement of the minimum dose to the 2cc volume of organs at risk (OAR) receiving the highest amount of radiation and summation across multiple treatment fractions to give a worst-case-scenario cumulative dose estimate. If the OAR from different fractions could be accurately co-registered using deformation, then a more accurate composite dose could be obtained.
OBJECTIVE: As a first step toward composite dose estimation, we sought to assess and improve the quality of bladder deformation using a technique called masking, which involves resetting the pixel values within a contour.
METHODS: CT scans from nine cervical cancer patients with bladders contoured by radiation oncologists were obtained, and the urethra near the bladder was contoured using the catheter as a fixed reference point. Three copies of each CT were made: the first was unaltered, the second had the bladder masked, and the third had the bladder masked at one pixel value and the rest of the body masked at a different pixel value. Using VelocityAI 2.8.1, the bladder was deformed onto the target (Fraction 1) planning CT from subsequent planning CTs in an attempt to match up the tissue from different fractions. To assess the accuracy of the deformation, several indices were used: the percent error of the deformed bladder volume from the expected volume, the conformality index, the Hausdorff distance, and the distance between the centers of the deformed urethra and the target urethra.
RESULTS: Deformation quality improved with masking. The standard deviation of the percent error was reduced from 18.1% with no masking to 4.3% with masking. Mean conformality increased from 0.83 with no masking, to 0.91 with the bladder masked, to 0.93 with body and bladder masked (P<0.001). The mean Hausdorff distance decreased from 13.8mm without masking, to 9.1mm with the bladder masked, to 5.7mm with body and bladder masked (P<0.001). The mean error in the urethra deformation increased from 4.3mm without masking, to 5.2mm with the bladder masked, to 6.6mm with body and bladder masked (P=0.08).
CONCLUSION: The accuracy of bladder deformation can be significantly improved by masking. With masking, the volume and location of the deformed bladder more closely approached that of the target bladder than without masking. Thus masking has the potential to improve the accuracy of dose deformation and composite dose calculation in adaptive brachytherapy.Southwestern Medical Foundatio
Statistical Analysis of Lumen Depreciation for LED Packages
No full textCommercial claims for LED-based products in terms of lumen maintenance are fully based on TM-21 extrapolations using LM-80 data. This chapter indicates that there may be a risk in doing this as TM-21 only relies on the behavior of the average LED degradation, instead of taking into account the degradation of all individual LEDs. Therefore, we propose a more profound statistical approach in order to make the appropriate step from TM-21 extrapolation to lumen maintenance on a product level. This is needed as some commercial claims are based on 10 years of warranty and some service bids provide periods of 20–25 years of operation. This chapter reviews the different approaches currently available to perform lumen maintenance extrapolations.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic Components, Technology and Material
Predicting Severe Hematologic Toxicity from Extended-Field Chemoradiation of Para-Aortic Nodal Metastases from Cervical Cancer
Get PDFThe 55th Annual Medical Student Research Forum at UT Southwestern Medical Center (Monday, January 17, 2017, 2-5 p.m., D1.600)BACKGROUND AND PURPOSE: To determine significant factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node (PALN) metastasis treated with concurrent chemoradiation with a specific focus on radiation dose to total bone marrow (BMTOT) and active bone marrow (BMACT). To create a nomogram using significant factors to predict HT in these patients.
MATERIAL AND METHODS: 38 Patients with cervical cancer and PALN metastasis who underwent 18F-FDG-PET / CT before treatment with extended field radiation therapy (EFRT) and concurrent cisplatin were analyzed. BMACT was defined as the region within BMTOT with a standardized uptake value (SUV) greater than or equal to the mean for the individual. Blood counts were collected weekly from the beginning of radiation treatment to the end of radiation treatment. HT was graded based on the guidelines set by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
RESULTS: 19 patients (50%) had Grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Patients who were obese (n=12) were less likely to get HT3+ compared to patients who were not obese (p=0.03) despite getting the same weight related dose of chemotherapy. Volume of BMTOT receiving 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 78.56% (p=0.01), 47.14% (p=0.00), and 20.36% (p=0.01) respectively. Volume of BMACT receiving 10 Gy, 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 95.50% (p=0.03), 80.52% (p=0.05), 59.64% (p=0.03), and 31.74% (p=0.01) respectively. Through logistic regression, the probability of developing HT3+ is given by the equation: Prob(HT3+) = 1 / (1 + exp(7.34 + 0.22*BMI - 0.44*Mean Dose to BMTOT)). Patients who had HT3+ received an average of 4 cycles of chemotherapy and 62 days of treatment time, significantly different than the 4.74 chemotherapy cycles and 53 days of treatment in patients without HT3+ (p=0.05, 0.00 respectively).
CONCLUSIONS: Both higher patient BMI and bone marrow irradiation were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients. Radiation parameters have been identified for cervical cancer patients with PALN involvement receiving EFRT concurrently with chemotherapy. Bone marrow sparing approaches for EFRT need to be addressed to improve patient care.Southwestern Medical Foundatio
Corrosion Sensitivity of LED Packages
No full textThe penetration of solid state lighting applications is due to the promise of a low-cost reliable solution by means of application of low- and mid-power LEDs. These LED packages are manufactured by making use of new processes and materials which in principle introduces a series of known and unknown failure modes. Corrosion is a specific failure mode which limits the lifetime, and hence manufacturers realize that their package integrity needs to be improved. This chapter describes the sensitivity to corrosion of LED packages. In the first part, an introduction to chemical incompatibility is given. In the second part, different sources of corrosion are distinguished. The construction of LED packages and their vulnerability to corrosion is described in the third part. In the fourth part of this chapter, testing methods are reviewed and their effectiveness to simulate real-life conditions. A series of experimental setups is used to explore the behavior of LED packages in contaminated environments. A combined experimental–theoretical approach is used to describe the performance in certain conditions of pollution. This will be covered in the fifth part. The last part describes a list of classes of chemicals, often found in electronics and construction materials for luminaires that may affect LED performance and for this reason should be avoided for the design of SSL solutions.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic Components, Technology and Material
Characterization and improvement of IFNY-[gamma] glycosylation in Chinese hamster ovary cell culture
No full textThesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1997.In title on t.p., "[gamma]" appears as the lower-case Greek letter.Includes bibliographical references (p. 178-190).Glycoproteins representing an important category of therapeutics for human health care, generally exist as a set of glycosylated variants exhibiting heterogeity with respect to both the proportion of potential glycosylation sites that are occupied (i.e., macroheterogeneity) and the oligosaccharide structures observed at each glycosylation site (i.e., microheterogeneity). Therefore, it is essential to characterize and. if possible, optimize the glycosylation profiles of recombinant glycoproteins to ensure their quality and consistency as effective pharmaceuticals and to meet increasing regulatory demands. In this study, the two potential N-linked glycosylation sites (i.e., Asn25 and Asn97) of recombinant human interferon-[gamma]y (IFNY-[gamma]) derived from Chinese hamster ovary (CHO) cell culture were characterized by a sensitive (- 1 [mu]) and rapid (- 3 h) analytical methodology employing a variety of tandem chromatographic techniques, capillary electrophoresis and mass spectrometry. Although complex biantennary glycans were the predominant structures at both glycosylation sites, Asn25 -linked glycans possessed higher proportions of tri- and tetraantennary structures and were exclusively fucosylated compared to glycans at Asn97. Although the proportions of glycan antennary structures were found to be relatively invariable throughout typical CHO batch cultures, the oligosaccharide structures were selectively altered by the introduction of various inhibitors of intracellular glycosylation pathways. For example, the use of dexamethasone, an inhibitor of the enzyme responsible for oligosaccharide branching, was found to decrease the proportions of tri- and tetraantennary glycan structures and, thus, improve the glycosylation homogeneity of CHO-derived IFNY-[gamma]. A critical aspect of glycosylation is sialylation since the presence of sialic acid can dramatically extend a glycoprotein's circulatory lifetime. The sialylation patterns of CHO-derived IFNY-[gamma] were characterized by RP-HPLC separations of glycosylation site-specific tryptic glycopeptides. IFNY-[gamma] displayed both site- and branch-specific differences in sialic acid content as Asn25-linked glycans and the Man([alpha]1-3) branch of the predominant complex biantennary glycan structures at each site were preferentially sialylated. Both incomplete intracellular sialylation and extracellular desialylation resulting from release of sialidase during cell lysis were found to determine the sialic acid content of the final product. Primatone RL, an animal tissue hydrolysate commonly employed as a serum substitute to stimulate cell growth, was found to have an adverse impact on intracellular sialylation of CHO-derived IFNY-[gamma] in both batch and fed-batch cultures. However, incomplete intracellular sialylation was minimized through feeding of Nacetylmannosamine (ManNAc), a synthetic orecursor of sialic acid. Feeding of 20 mM ManNAc reduced the proportion of undersialylated glycan structures by 50%. Radiolabeled MarNAc was utilized to confirm that the supplemental ManNAc was incorporated into IFNY-[gamma] as sialic acid. The intracellular pool of CMP-sialic acid. the nucleotide sugar substrate for sialyltransferase, was also extracted and quantitated by RP-HPLC. Although feeding of 20 mM ManNAc increased the intracellular pool of CMP-sialic acid nearly 30-fold, in vitro incubation of isolated Golgi with radiolabeled CMP-sialic acid revealed a limitation for transport of the substrate to the site of sialylation.by Xuejun (Sherry) Gu.Ph.D
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