Tak W. Kee

Bio: Tak W. Kee is an academic researcher from University of Adelaide. The author has contributed to research in topics: Exciton & Singlet fission. The author has an hindex of 29, co-authored 74 publications receiving 3294 citations. Previous affiliations of Tak W. Kee include University of Texas at Austin & National Institute of Standards and Technology.

The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds

Abstract: Thioflavin T (ThT) dye fluorescence is used regularly to quantify the formation and inhibition of amyloid fibrils in the presence of anti-amyloidogenic compounds such as polyphenols. However, in this study, it was shown, using three polyphenolics (curcumin, quercetin and resveratrol), that ThT fluorescence should be used with caution in the presence of such exogenous compounds. The strong absorptive and fluorescent properties of quercetin and curcumin were found to significantly bias the ThT fluorescence readings in both in situ real-time ThT assays and single time-point dilution ThT-type assays. The presence of curcumin at concentrations as low as 0.01 and 1 mum was sufficient to interfere with the ThT fluorescence associated with fibrillar amyloid-beta(1-42) (0.5 mum) and fibrillar reduced and carboxymethylated kappa-casein (50 mum), respectively. The ThT fluorescence associated with fibrillar amyloid-beta(1-42) was also biased using higher concentrations of resveratrol, a polyphenol that is not spectroscopically active at the wavelengths of ThT fluorescence, implying that there can be direct interactions between ThT and the exogenous compound and/or competitive binding with ThT for the fibrils. Thus, in all cases where ThT is used in the presence of an exogenous compound, biases for amyloid-associated ThT fluorescence should be tested, regardless of whether the additive is spectroscopically active. Simple methods to conduct these tests were described. The Congo red spectral shift assay is demonstrated as a more viable spectrophotometric alternative to ThT, but allied methods, such as transmission electron microscopy, should also be used to assess fibril formation independently of dye-based assays. Structured digital abstract: * MINT-7259867: RCMkappa-CN (uniprotkb:P02668) and RCMkappa-CN (uniprotkb:P02668) bind (MI:0407) by electron microscopy (MI:0040) * MINT-7258930: RCMkappa-CN (uniprotkb:P02668) and RCMkappa-CN (uniprotkb:P02668) bind (MI:0407) by fluorescence technologies (MI:0051) * MINT-7259878: Amyloid beta (uniprotkb:P05067) and Amyloid beta (uniprotkb:P05067) bind (MI:0407) by fluorescence technologies (MI:0051).

Acoustic-optical phonon up-conversion and hot-phonon bottleneck in lead-halide perovskites.

Abstract: The hot-phonon bottleneck effect in lead-halide perovskites (APbX3) prolongs the cooling period of hot charge carriers, an effect that could be used in the next-generation photovoltaics devices. Using ultrafast optical characterization and first-principle calculations, four kinds of lead-halide perovskites (A=FA+/MA+/Cs+, X=I-/Br-) are compared in this study to reveal the carrier-phonon dynamics within. Here we show a stronger phonon bottleneck effect in hybrid perovskites than in their inorganic counterparts. Compared with the caesium-based system, a 10 times slower carrier-phonon relaxation rate is observed in FAPbI3. The up-conversion of low-energy phonons is proposed to be responsible for the bottleneck effect. The presence of organic cations introduces overlapping phonon branches and facilitates the up-transition of low-energy modes. The blocking of phonon propagation associated with an ultralow thermal conductivity of the material also increases the overall up-conversion efficiency. This result also suggests a new and general method for achieving long-lived hot carriers in materials.

Simple approach to one-laser, broadband coherent anti-Stokes Raman scattering microscopy.

Abstract: Coherent anti-Stokes Raman scattering (CARS) microscopy is emerging as a powerful method for imaging materials and biological systems, partly because of its noninvasiveness and selective chemical sensitivity. However, its full potential for species-selective imaging is limited by a restricted spectral bandwidth. Recent increases in bandwidth are promising but still are not sufficient for the level of robust component discrimination that would be needed in a chemically complex milieu found, for example, in intracellular and extracellular environments. We demonstrate a truly broadband CARS imaging instrument that we use to acquire hyperspectral images with vibrational spectra over a bandwidth of 2500 cm(-1) with a resolution of 13 cm(-1).

Encapsulation of curcumin in cationic micelles suppresses alkaline hydrolysis

Abstract: The alkaline hydrolysis of curcumin was studied in three types of micelles composed of the cationic surfactants cetyl trimethylammonium bromide (CTAB) and dodecyl trimethylammonium bromide (DTAB) and the anionic surfactant sodium dodecyl sulfate (SDS). At pH 13, curcumin undergoes rapid degradation by alkaline hydrolysis in the SDS micellar solution. In contrast, alkaline hydrolysis of curcumin is greatly suppressed in the presence of either CTAB or DTAB micelles, with a yield of suppression close to 90%. The results from fluorescence spectroscopic studies reveal that while curcumin remains encapsulated in CTAB and DTAB micelles at pH 13, curcumin is dissociated from the SDS micelles to the aqueous phase at this pH. The absence of encapsulation and stabilization in the SDS micellar solution results in rapid hydrolysis of curcumin.

Effective stabilization of curcumin by association to plasma proteins: human serum albumin and fibrinogen.

Abstract: The use of curcumin as an effective wound healing agent is of significant interest currently. It is well established that curcumin undergoes rapid degradation in physiological buffer by hydrolysis. The means by which curcumin is stabilized at the wound site to enable healing is poorly understood because blood plasma is composed of approximately 92% water. Plasma proteins, which constitute the remaining 6-8%, has been shown to stabilize curcumin. It is, however, still unclear which proteins are responsible for this phenomenon. In this study, the effects of major plasma proteins, which include human serum albumin (HSA), fibrinogen, immunoglobulin G (IgG), and transferrin, on stabilizing curcumin are investigated. In particular, we investigate their effects on the hydrolysis of curcumin at pH 7.4. In the presence of both transferrin and IgG, curcumin continues to undergo rapid hydrolysis but this reaction is suppressed by the presence of either HSA or fibrinogen with an impressive yield of approximately 95%. Furthermore, the binding constants of curcumin to HSA and fibrinogen are on the order of 10(4) and 10(5) M(-1), respectively. The binding constants of transferrin and IgG, however, are at least 1 order of magnitude less than those of HSA and fibrinogen. The results support that strong binding occurs at the hydrophobic moieties of HSA and fibrinogen, excluding water access. Therefore, strong interactions with HSA and fibrinogen inhibit hydrolysis of curcumin and in turn lead to effective suppression of degradation.

Fast parallel algorithms for short-range molecular dynamics

Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Organic solar cells based on non-fullerene acceptors.

Abstract: Organic solar cells (OSCs) have been dominated by donor:acceptor blends based on fullerene acceptors for over two decades. This situation has changed recently, with non-fullerene (NF) OSCs developing very quickly. The power conversion efficiencies of NF OSCs have now reached a value of over 13%, which is higher than the best fullerene-based OSCs. NF acceptors show great tunability in absorption spectra and electron energy levels, providing a wide range of new opportunities. The coexistence of low voltage losses and high current generation indicates that new regimes of device physics and photophysics are reached in these systems. This Review highlights these opportunities made possible by NF acceptors, and also discuss the challenges facing the development of NF OSCs for practical applications.

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Abstract: : The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

The Essential Medicinal Chemistry of Curcumin

Abstract: Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.