49 research outputs found
The openness of pluripotent epigenome - Defining the genomic integrity of stemness for regenerative medicine
This article is an editorial, and it doesn't include an abstract. Full text of this article is available in HTML and PDF.Cite this article as: Parsons XH. The openness of pluripotent epigenome - Defining the genomic Integrity of stemness for regenerative medicine. Int J Cancer Ther Oncol 2014; 2(1):020114.DOI: http://dx.doi.org/10.14319/ijcto.0201.1
Gas phase studies of hypoxanthine:
Hypoxanthine 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
Implementation of General Coupling Model of Electromigration in ANSYS
In this paper, a recently developed theory - general coupling model of electromigration, is implemented in ANSYS. We first identify several errors provided in ANSYS manual for electromigration modeling. Then the general coupling model is implemented in ANSYS and the detailed description is presented. Finally, a 1-D confined metal line with a perfectly blocking condition is presented as a benchmark problem, in which the finite element solutions are in excellent agreement with the analytical solutions.Accepted author manuscriptElectronic Components, Technology and Material
Direct Conversion of Pluripotent Human Embryonic Stem Cells Under Defined Culture Conditions into Human Neuronal or Cardiomyocyte Cell Therapy Derivatives
Reviving Cell-Based Regenerative Medicine for Heart Reconstitution with Efficiency in Deriving Cardiac Elements from Pluripotent Human Embryonic Stem Cells
Constraining the Pluripotent Fate of Human Embryonic Stem Cells for Tissue Engineering and Cell Therapy – The Turning Point of Cell-Based Regenerative Medicine
To date, the lack of a clinically-suitable source of engraftable human stem/progenitor cells with adequate neurogenic potential has been the major setback in developing safe and effective cell-based therapies for regenerating the damaged or lost CNS structure and circuitry in a wide range of neurological disorders. Similarly, the lack of a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential has been the major setback in regenerating the damaged human heart. Given the limited capacity of the CNS and heart for self-repair, there is a large unmet healthcare need to develop stem cell therapies to provide optimal regeneration and reconstruction treatment options to restore normal tissues and function. Derivation of human embryonic stem cells (hESCs) provides a powerful in vitro model system to investigate molecular controls in human embryogenesis as well as an unlimited source to generate the diversity of human somatic cell types for regenerative medicine. However, realizing the developmental and therapeutic potential of hESC derivatives has been hindered by the inefficiency and instability of generating clinically-relevant functional cells from pluripotent cells through conventional uncontrollable and incomplete multi-lineage differentiation. Recent advances and breakthroughs in hESC research have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for de novo derivation and maintenance of clinical-grade pluripotent hESCs and lineage-specific differentiation of pluripotent hESCs by small molecule induction. Retinoic acid was identified as sufficient to induce the specification of neuroectoderm direct from the pluripotent state of hESCs and trigger a cascade of neuronal lineage-specific progression to human neuronal progenitors and neurons of the developing CNS in high efficiency, purity, and neuronal lineage specificity by promoting nuclear translocation of the neuronal specific transcription factor Nurr-1. Similarly, nicotinamide was rendered sufficient to induce the specification of cardiomesoderm direct from the pluripotent state of hESCs by promoting the expression of the earliest cardiac-specific transcription factor Csx/Nkx2.5 and triggering progression to cardiac precursors and beating cardiomyocytes with high efficiency. This technology breakthrough enables direct conversion of pluripotent hESCs into a large supply of high purity neuronal cells or heart muscle cells with adequate capacity to regenerate CNS neurons and contractile heart muscles for developing safe and effective stem cell therapies. Transforming pluripotent hESCs into fate-restricted therapy derivatives dramatically increases the clinical efficacy of graft-dependent repair and safety of hESC-derived cellular products. Such milestone advances and medical innovations in hESC research allow generation of a large supply of clinical-grade hESC therapy derivatives targeting for major health problems, bringing cell-based regenerative medicine to a turning poin
A novel lifetime prediction for integrated LED lamps by electronic-thermal simulation
In this paper, an integrated LED lamp with an electrolytic capacitor-free driver is considered to study the coupling effects of both LED and driver's degradations on lamp's lifetime. An electrolytic capacitor-less buck-boost driver is used. The physics of failure (PoF) based electronic thermal simulation is carried out to simulate the lamp's lifetime in three different scenarios: Scenario 1 considers LED degradation only, Scenario 2 considers the driver degradation only, and Scenario 3 considers both degradations from LED and driver simultaneously. When these two degradations are both considered, the lamp's lifetime is reduced by about 22% compared to the initial target of 25,000 h. The results of Scenario 1 and 3 are close to each other. Scenario 2 gives erroneous results in terms of luminous flux as the LED's degradation over time is not taken into consideration. This implies that LED's degradation must be taken into considerations when LED and driver's lifetimes are comparable.Accepted author manuscriptElectronic Components, Technology and Material
A review of small heat pipes for electronics
Heat pipes (HPs) have received considerable attention in recent decades, especially in the field of cooling electronics, which requires the removal of added heat from an area of limited volume to the environment. Small HPs are widely used in electronic applications, which are normally limited by the compact structure and dimensions of the electronic device. Among small HPs, mini/micro HPs and two-phase loops (TPLs) with mini/micro wicks, including loop HPs (LHPs) and capillary pumped loops (CPLs), are preferred for their high efficiency, small dimensions, and compatible process with semiconductor devices. Particularly, TPLs possess all of the main advantages of traditional HPs with the addition of special properties that enable the transfer of heat for distances up to several metres at any orientation in the gravity field. Further, small vapour chambers (VCs), also referred to as flat HPs, are excellent candidates for electronic heat spreaders due to their light weight, geometric flexibility, and extremely high thermal conductivities. Because silicon is widely used in electronics, it is a preferred material for mini/micro HPs along with TPLs. Moreover, polymer-based small HPs are highly attractive for further development as they are inexpensive and easy to fabricate. Because the smaller wicks supply a greater capillary force, nano wicks, such as carbon nanotubes (CNTs), may represent the future of HPs due to their potentially outstanding characteristics. In this work, a review of small HPs, including their design, analysis, and fabrication, is presented.Accepted author manuscriptElectronic Components, Technology and Material
Successful treatment of a paraneoplastic pemphigus in a teenager using plasmapheresis, corticosteroids and tumour resection
Paraneoplastic pemphigus (PNP) is a severe autoimmune blistering disease. Bronchiolitis obliterans (BO) is a common complication of PNP, is the major cause of death. PNP is rarely seen before the age of 18 years, and the prognosis is poor because of BO. We report a 16-year-old girl with the typical findings of PNP associated with Castleman's tumour. She was treated with tumour resection in combination with plasmapheresis and corticosteroids. Fifteen months after the operation, the patient had recovered without the development of BO.DermatologySCI(E)PubMed1ARTICLE7752-7543
Overdriving reliability of chip scale packaged LEDs: Quantitatively analyzing the impact of component
The objective of this study is to quantitatively evaluate the impacts of LED components on the overdriving reliability of high power white LED chip scale packages (CSPs). The reliability tests under room temperature are conducted over 1000 h in this study on CSP LEDs with overdriving currents. A novel method is proposed to investigate the impact of various components, including blue die, phosphor layer, and substrate, on the lumen depreciation of CSP LEDs after aging test. The electro-optical measurement results show that the overdriving current can lead to both massive light output degradation and significant color shift of CSP LEDs. The quantitative analysis results show that the phosphor layer is the major contributor to the failure in early period aging test. For the long-term reliability, the degradations of phosphor and reflectivity of substrate contribute significantly on lumen depreciation. The proposed reliability assessment method with overdriving loadings can be usefully implemented for LED manufacturers to make a cost- and effective-decision before mass production.Accepted author manuscriptElectronic Components, Technology and Material
