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  • Publication
    STUDY THE INVOLVEMENT OF LYSOSOMAL CALCIUM SIGNALING IN THE ANTI-CANCER ACTIVITY OF THE LANTHANIDE PR-MPO
    (2015-01-14) LIU DAN; NUS GRAD SCH FOR INTEGRATIVE SCI & ENGG; PERVAIZ, SHAZIB
    WE SYNTHESIZED A CONJUGATE OF THE LANTHANIDE, PRASEODYMIUM (141PR), AND OBSERVED REMARKABLE ANTI-TUMOR ACTIVITY IN 2 MURINE XENOGRAFT MODELS (COLORECTAL AND PROSTATE CANCER), WITH MINIMAL OFF TARGET EFFECTS. IMPORTANTLY, PR-MERCAPTOPYRIDINE OXIDE (PR-MPO) ELICITED STRONG ANTI-CANCER ACTIVITY (IC50~2.5UM) AGAINST A HOST OF HUMAN CANCER CELL LINES INCLUDING CISPLATIN RESISTANT, P53-/- AND/OR BAX-/- VARIANTS. INTERESTINGLY, PR-MPO INDUCED A SIGNIFICANT INCREASE IN INTRACELLULAR CALCIUM FLUORESCENCE, MEASURED BY TIME RESOLVED LIVE IMAGING, HOWEVER, UNLIKE THAPSIGARGIN, THE INCREASE IN CALCIUM WAS NOT MEDIATED BY ER CALCIUM STORES. INSTEAD, A SIGNIFICANT INCREASE IN CALCIUM FLUORESCENCE (PUNCTA) WAS OBSERVED WITHIN MINUTES, A PATTERN DISTINCTLY DIFFERENT FROM THE DIFFUSE CYTOSOLIC INCREASE UPON DEPLETING ER CALCIUM. NOTABLY, CHELATION OF EXTRACELLULAR CALCIUM ABROGATED THE INCREASE IN INTRACELLULAR CALCIUM AS WELL AS RESCUED CELLS FROM PR-MPO-INDUCED CELL DEATH, THUS SUGGESTING THE INVOLVEM
  • Publication
    Probing Heat Transport in Nanowires Using a Focused Electron Beam Heating Technique
    (2014-03-27) LIU DAN; NUS GRAD SCH FOR INTEGRATIVE SCI & ENGG; THONG THIAM LEONG, JOHN; LI BAOWEN
    The understanding of nanoscale thermal transport plays an important role in the thermal management of modern integrated circuits and in the development of thermoelectric materials. Numerous experimental and theoretical works have emerged during the past decade, deepening the understanding of how heat flows in nanostructures. However the tools available to the experimentalist to probe thermal transport at the nanoscale are still quite limited. In this thesis, a new thermal measurement technique that is capable of profiling nanowire thermal resistance with a spatial resolution of nanometers is developed. The technique uses a focused electron beam as a localized heat source to establish a temperature gradient along the nanowire. The heat fluxes from the two ends of the nanowire are measured using platinum resistance thermometers on two suspended thermally-isolated islands from which the local thermal conductivity can be derived. This electron beam heating technique was then used to study three material systems, namely helium-ion irradiated Si nanowires, Si1-xGex/NiSi1-xGex bamboo-structured nanowires and Si/NixSiy nanowire heterointerfaces. We show that by a single scan of the electron beam along the nanowire, the local thermal conductance altered by non-uniformities in the nanowire, such as local defects, change of surface roughness and variations in diameter, can be discriminated. Moreover, the long-standing problem of ill-defined thermal contact resistance between the nanowire and the two temperature sensors, which is a serious drawback in the conventional thermal bridge method, is avoided. This technique is also capable of measuring the thermal boundary resistance across epitaxial material `interfaces in the nanowire. This technique thus provides a powerful tool for studying the underlying physics of thermal transport in nanostructures, which will in turn improve the thermal models adopted in the design of nano-devices, and inform the fabrication of nanostructured thermoelectric materials with enhanced performance.