An Adaptive Role for DNA Double-Strand Breaks in Hippocampus-Dependent Learning and Memory

DNA double-strand breaks (DSBs), classified as the most harmful type of DNA damage based on the complexity of repair, lead to apoptosis or tumorigenesis. In aging, DNA damage increases and DNA repair decreases. This is exacerbated in disease, as post-mortem tissue from patients diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) show increased DSBs. A novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity leads to increases in DSBs and upregulation of IEGs, while increasing DSBs and inhibiting DSB repair impairs long-term memory and alters IEG expression. Consistent with this pattern, mice carrying dominant AD mutations have increased baseline DSBs, and impaired DSB repair is observed. These data suggest an adaptive role for DSBs in the central nervous system and dysregulation of DSBs and/or repair might drive age-related cognitive decline (ACD), MCI, and AD. In this review, we discuss the adaptive role of DSBs in hippocampus-dependent learning, memory, and IEG expression. We summarize IEGs, the history of DSBs, and DSBs in synaptic plasticity, aging, and AD. DSBs likely have adaptive functions in the brain, and even subtle alterations in their formation and repair could alter IEGs, learning, and memory.     

Bacteria-Responsive Multidrug Delivery Nanosystem for Combating Long-Term Biofilm-Associated Infections

Microbial biofilm formation on implantable devices causes chronic infections that cannot be treated with existing antimicrobials. Quorum sensing inhibitors (QSIs) have recently emerged as novel antimicrobials for the prevention of biofilm formation. But blocking QS alone is insufficient to inhibit biofilm-associated chronic infections. Herein, chitosan hollow nanospheres are capped by bacteria-responsive β-casein to form a synergistic antifouling nanosystem consisting of a QSI and bactericide. β-casein is degraded by protease in a bacteria-colonized microenvironment in situ thus, QSI and bactericide are released sequentially. The release of QSI sensitises bacteria effectively through reduction of surface hydrophobicity, eDNA content, and lipopolysaccharide production in biofilms, amplifying the chemotherapeutic action of the bactericide. Compared to the uncoated surface, the coated surface inhibits biofilm formation and removes preformed biofilms of Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus by 1.8 logs and 1.9 logs of biomass inhibition, respectively. The coated catheters are found to stay clean for 30 days under artificial urine flow, while the uncoated catheters are clogged by bacterial biofilms within 5 days. Finally, the long term antifouling activity in vivo is confirmed. Overall, the nanosystem is devoted to making urinary catheters resistant to bacterial biofilm formation for the long term.     

Cascode Monolithic DC-DC Converter for Reliable Operation at High Input Voltages

A CMOS OTA-C low-pass notch filter for EEG application is described. The pass-band covers four bands of brain wave and provides more than 65 dB attenuation for the 50 Hz power line interference. The OTA works in the weak inversion region and a low transconductance of 3 nA/V is achieved. The low transconductance enables using small capacitors in the OTA-C filter so that the filter is suitable for the multi-channel EEG integrated circuits. The measured results show the good performance of the filter for filtering the noise in acquired EEG signals. Xinbo Qian received the B.Sc. degree from Beijing Institute of Technology, P.R. China, in 1991 and M.Sc. degree from Institute of Physics, Chinese Academy of Sciences, in 1996. From 1996 to 1999, she was a research engineer in the Institute of Acoustics, Chinese Academy of Sciences, worked on the sonar signal receiving and processing systems. Since 1999, she has been pursuing the Ph.D. degree in Electrical and Computer Engineering department, National University of Singapore, with research direction on on-chip readout circuits for microbolometer focal plane arrays. Now she is employed by Department of Mechanical Engineering and Division of Bioengineering, National University of Singapore as a research fellow. Her research interest is low-noise integrated circuits design and bio-medical sensor electronics, including electroencephalography IC, magnetocardiography IC, low-noise amplifier, filter and data converters etc. Yong Ping Xu graduated from Nanjing University, P.R. China in 1977. He received his Ph.D. from University of New South Wales (UNSW) Australia, in 1994. From 1978 to 1987, he was with Qingdao Semiconductor Research Institute, P.R. China, initially as an IC design engineer, and later the deputy R&D manager and the Director. From 1989 to 1992, he was working on silicon diode based infrared detectors towards his Ph.D. at School of Electrical Engineering, UNSW Australia. From 1993 to 1995, he worked on an industry collaboration project with GEC Marconi, Sydney, Australia, at the same university, involved in design of sigma-delta ADCs. He was a lecturer at University of South Australia, Adelaide, Australia from 1996 to 1998. He has been with the Department of Electrical and Computer Engineering, National University of Singapore since June 1998 and is now an Associate Professor. His general research interests are in the areas of mixed-signal and RF integrated circuits, and integrated MEMS and sensing systems. His current focuses are high-speed wideband ADC, UWB front-end circuits and low-power low-voltage integrated circuits for biomedical applications. He is a Senior Member of IEEE. Xiaoping Li received his Ph.D. degree from Department of Mechanical and Manufacturing Engineering, University of New South Wales, Australia in 1991, and joined the National University of Singapore in 1992, where he is currently an Associate Professor with the Department of Mechanical Engineering and Division of Bioengineering. He was a visiting professor of Tokyo Institute of Technology, Japan in 2000, and visiting professor of Georgia Institute of Technology, USA in 2001. He is a member of American Society of Mechanical Engineers (ASME), a senior member of Society of Manufacturing Engineering (SME) and a senior member of North American Manufacturing Research Institute/SME, and is currently the Chairman of SME Singapore Chapter. His current research interests include neurosensors and nanomachining. He is a guest editor of International Journal of Computer Applications in Technology, USA. He is a regular reviewer of the ASME Journal of Manufacturing Engineering, USA, Transactions of NAMRI/SME, USA, Journal of materials processing technology, UK, International Journal of Machine Tools and Manufacture, UK, and IMechE Journal of Engineering Manufacture, UK.     

Viscosity of Porous Glasses

Viscosity of porous glasses has been derived from the elastic stress analysis, using the viscous analogy. Viscosity as a function of porosity has been estimated for spherical as well as for arbitrary pore geometry. Since the pore geometry changes during sintering, a shape factor that varies with pore geometry has been considered to predict the viscosity–porosity relationship. Viscosity as a function of porosity was measured on cordierite-type glass by isothermal sinter-forging experiments and data showed good agreement with the analysis. Experimental data from literature on viscosity as a function of porosity on two other glasses also show good agreement with the analysis.     

Numerical and experimental analysis of large passivation opening for solder joint reliability improvement of micro SMD packages

In this paper, using a recently developed solder fatigue model for wafer level-chip scale package (WL-CSP), we investigated the improvement on solder joint reliability for a 8-bump micro SMD package by enlarging the passivation layer opening at the solder–die interface. The motivation to enlarge the passivation opening is to reduce the severity of the stress concentration caused by the original design, and also to increase the contact area between the solder bump and aluminum bump pad. It was confirmed in the thermal shock test that with the new design, package fatigue life improved by more than 70%. To numerically predict this improvement represents a unique challenge to the modeling. This is because in order to capture the slightest geometrical difference on the order of a few microns between the two designs, the multiple-layer solder-die interface needs to be modeled using extremely fine mesh, while the overall dimensions of the package and the test board are on the order of millimeters. To bridge this tremendous gap in geometry, a single finite element model that incorporates all necessary geometrical details is deemed computationally prohibitive and impractical. In this paper, we applied a global–local modeling scheme that was also suggested by others [1, 2 and 3]. The global model contains the complete package with much simplified solder–die interface whereas the local model includes only one solder joint, but with detailed solder–die interface. Unlike most global–local models proposed by others, we included time-independent plasticity and temperature-dependent materials in the global model. This greatly improved model correlation accuracy with only moderate increase in run time. Energy-based solder fatigue model was used to correlate the inelastic strain energy with the package fatigue life. In an earlier study [4], we have found that Darveaux’s equations tended to be conservative when applied to the micro SMD, and hence new correlations based on curve-fitting the test data were derived. In this paper, we used the newly derived equation and achieved less than 20% error in N₅₀ life for both designs, which is on par with Darveaux’s equations when used for BGAs. The analysis also revealed two factors that may account for the life improvement. First, a slight decrease in inelastic energy dissipation after enlarging the passivation opening. Second, the shift of the crack initiation location which leads to longer crack growth length for the new design. The second factor was also independently confirmed by the failure analysis.     

Channel capacity with suboptimal adaptation technique over generalized-K fading using marginal moment generating function

In this paper we have computed the channel capacity for suboptimal adaptation technique over the generalized-K fading environment. The analytical expression for channel capacity in case of the truncated channel inversion with fixed rate (C_TCIFR) has been exploited in terms of marginal moment generating function (MMGF) and its performance is evaluated over the generalized-K faded environment. The MMGF based approach for the computation of channel capacity has been validated with the reported literature for channel capacity in case of the channel inversion with fixed rate using the suboptimal adaptive technique.     

Development of Metallic Hermetic Sealing for MEMS Packaging for Harsh Environment Applications

Hermetic sealing of microelectromechanical system sensors is indispensable to ensure their reliable operation and also to provide protection during fabrication. This work proposes two prospective candidates for hermetic sealing for rugged environment applications, i.e., Al-Ge and Pt-In. Al-Ge was chosen due to its compatibility with complementary metal–oxide–semiconductor technology. Pt-In possesses the highest remelting temperature among all the solder systems, which is desired for high-temperature applications in both the energy and aerospace industries. The various bonding parameters for Al-Ge eutectic bonding and Pt-In transient liquid-phase (TLP) bonding have been optimized, and their influence on the bond quality is reported. Optimization of bonding parameters has been carried out with the objective of ensuring void-free bonds. A new configuration for stacking Al-Ge thin films has been demonstrated to tackle the issue of loss of Ge prior to bonding, since native Ge oxides are soluble in deionized water. The impact of solid-state aging prior to Al-Ge eutectic bonding has been investigated. The method of tailoring the phases in the Pt-In joint is also discussed. The prospects and constraints of eutectic and TLP bonding from the hermeticity perspective are discussed in detail. Furthermore, changes in the microstructure under aging at 300°C up to 500 h and the resulting influence on the mechanical properties are presented. The overall finding of this work is that Al-Ge can achieve better mechanical and hermetic performance for high-temperature applications.     

Reliability of Au-Ge and Au-Si Eutectic Solder Alloys for High-Temperature Electronics

High-temperature electronics will facilitate deeper drilling, accessing harder-to-reach fossil fuels in oil and gas industry. A key requirement is reliability under harsh conditions for a minimum continuous operating time of 500?h at 300°C. Eutectic solder alloys are generally favored due to their excellent fatigue resistance. Performance of Au-Ge and Au-Si eutectic solder alloys at 300°C up to 500?h has been evaluated. Nanoindentation results confirm the loss of strength of Au-Ge and Au-Si eutectic solder alloys during thermal aging at 300°C, as a result of grain coarsening. However, the pace at which the Au-Ge eutectic alloy loses its strength is much slower when compared with Au-Si eutectic alloy. The interfacial reactions between these eutectic solder alloys and the underbump metallization (UBM), i.e., electroless nickel immersion gold (ENIG) UBM and Cu/Au UBM, have been extensively studied. Spalling of Au₃Cu intermetallic compound is observed at the interface between Au-Ge eutectic solder and the Cu/Au UBM, when aged at 300°C for 500?h, while the consumption of ENIG UBM is nominal. Unlike the Au-Si solder joint, hot ball shear testing at high temperature confirmed that the Au-Ge joint on ENIG UBM, when aged at 300°C for 500?h, could still comply with the minimum qualifying bump shear strength based on the UBM dimension used in this work. Thus, it has been determined that, among these two binary eutectic alloys, Au-Ge eutectic alloy could fulfill the minimum requirement specified by the oil and gas exploration industry.