Using a generalized scheme of multiple traps, thermoluminescence (TL) glow curves are calculated for different sets of systems parameters. In particular, the conditions under which glow peaks of first-order kinetics are produced are highlighted. The major findings and conclusions are as follows. (1) In the generalized scheme the glow peaks always reduce to first order at low trap occupancies. It is therefore suggested that the peak analysis to determine the parameters should be carried out only at low doses. (2) Glow peaks which follow first-order kinetics can be obtained irrespective of whether the recombination rate is faster, equal to or slower than the retrapping rate (Rret). (3) Quasi-equilibrium (QE) of free carriers in the delocalized band, which is the essential condition for the derivation of the conventional analytical expressions of TL and thermally stimulated conductivity, can be realized irrespective of whether RrecRret. (4) The realization of the QE condition depends on the concentrations of the traps and the recombination centres (RCs) and their cross sections for free carrier capture. It is discussed and shown that, in doped insulating and semiconducting materials, the values of these parameters are sufficiently high for the QE condition to be comfortably held. It is thus concluded that the doubts raised by earlier workers regarding the validity of the QE assumption in the derivation of the analytical expressions are unnecessary as far as these materials are concerned. (5) It is shown that a system in which some of the untrapped charge carriers recombine within the germinate centres and some become delocalized may satisfactorily explain the mechanism of TL emission in most of the phosphors. The properties of first-order, supralinearity and pre-dose sensitization may be easily explained under the framework of this system. (6) Conclusions (2) and (3) above disprove those of earlier workers who had concluded that QE and fast retrapping together do not form a consistent set of conditions and that the apparent dominance of first-order kinetics in nature is due to slow retrapping.

Choline transporter-like protein 1 (CTL1) is highly expressed in glioma cells, and inhibition of CTL1 function induces apoptotic cell death. Therefore, CTL1 is a potential target molecule for glioma therapy. Here, we investigated the therapeutic mechanism underlying the antitumor effects of Amb4269951, a recently discovered novel CTL1 inhibitor, in the human glioma cell line U251MG, and evaluated its in vivo effects in a mouse xenograft model. Amb4269951 inhibited choline uptake and cell viability and increased caspase-3/7 activity. CTL1-mediated choline uptake is associated with cell viability, and the functional inhibition of CTL1 by Amb4269951 may promote apoptotic cell death via ceramide-induced suppression of the expression of survivin, an apoptotic inhibitory factor. Finally, Amb4269951 demonstrated an antitumor effect in a mice xenograft model by significantly inhibiting tumor growth without any weight loss. Amb4269951 is the lead compound in the treatment of glioma and exhibits a novel therapeutic mechanism. These results may lead to the development of novel anticancer drugs targeting the choline transporter CTL1, which has a different mechanism of action than conventional anticancer drugs against gliomas.

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Non-first order (FO) kinetics models are of three types; second order (SO), general order (GO) and mixed order (MO). It is shown that all three of these have constraints in their energy level schemes and their applicable parameter values. In nature such restrictions are not expected to exist. The thermoluminescence (TL) glow peaks produced by these models shift their position and change their shape as the trap occupancies change. Such characteristics are very unlike those found in samples of real materials. In these models, in general, retrapping predominates over recombination. It is shown that the quasi-equilibrium (QE) assumption implied in the derivation of the TL equation of these models is quite valid, thus disproving earlier workers' conclusion that QE cannot be held under retrapping dominant conditions. However notwithstanding their validity, they suffer from the shortcomings as stated above and have certain lacunae. For example, the kinetic order (KO) parameter and the pre-exponential factor which are assumed to be the constant parameters of the GO kinetics expression turn out to be variables when this expression is applied to plausible physical models. Further, in glow peak characterization using the GO expression, the quality of fit is found to deteriorate when the best fitted value of KO parameter is different from 1 and 2. This means that the found value of the basic parameter, namely the activation energy, becomes subject to error. In the MO kinetics model, the value of the KO parameter α would change with dose, and thus in this model also, as in the GO model, no single value of KO can be assigned to a given glow peak. The paper discusses TL of real materials having characteristics typically like those of FO kinetics. Theoretically too, a plausible physical model of TL emission produces glow peaks which have characteristics of FO kinetics under a wide variety of parametric combinations. In the background of the above findings, it is suggested that the kinetics analysis of the TL glow curves should be carried out straightforwardly assuming FO kinetics.

Choline, an organic cation, is one of the biofactors that play an important role in the structure and the function of biological membranes, and it is essential for the synthesis of phospholipids. Choline positron emission tomography-computed tomography (PET/CT) provides useful information for the imaging diagnosis of cancers, and increased choline accumulation has been identified in a variety of tumors. However, the molecular mechanisms of choline uptake and choline transporters in pancreatic cancer have not been elucidated. Here, we examined molecular and functional analyses of choline transporters in human pancreatic-cancer cell line MIA PaCa-2 and the elucidation of the action mechanism behind the antitumor effect of novel choline-transporter-like protein 1 (CTL1) inhibitors, Amb4269951 and its derivative Amb4269675. CTL1 and CTL2 mRNAs were highly expressed in MIA PaCa-2 cells, and CTL1 and CTL2 proteins were localized in the plasma membrane and the intracellular compartments, respectively. Choline uptake was characterized by Na+-independence, a single-uptake mechanism, and inhibition by choline-uptake inhibitor HC-3, similar to the function of CTL1. These results suggest that the uptake of extracellular choline in MIA PaCa-2 cells is mediated by CTL1. Choline deficiency and HC-3 treatment inhibited cell viability and increased caspase 3/7 activity, suggesting that the inhibition of CTL1 function, which is responsible for choline transport, leads to apoptosis-induced cell death. Both Amb4269951 and Amb4269675 inhibited choline uptake and cell viability and increased caspase-3/7 activity. Ceramide, which is increased by inhibiting choline uptake, also inhibited cell survival and increased caspase-3/7 activity. Lastly, both Amb4269951 and Amb4269675 significantly inhibited tumor growth in a mouse-xenograft model without any adverse effects such as weight loss. CTL1 is a target molecule for the treatment of pancreatic cancer, and its inhibitors Amb4269951 and Amb4269675 are novel lead compounds.