DMT1 Inhibitors Kill Cancer Stem Cells by Blocking Lysosomal Iron Translocation

Cancer stem cells (CSC) constitute a cell subpopulation in solid tumors that is responsible for resistance to conventional chemotherapy, metastasis and cancer relapse. The natural product Salinomycin can selectively target this cell niche by directly interacting with lysosomal iron, taking advantage of upregulated iron homeostasis in CSC. Here, inhibitors of the divalent metal transporter 1 (DMT1) have been identified that selectively target CSC by blocking lysosomal iron translocation. This leads to lysosomal iron accumulation, production of reactive oxygen species and cell death with features of ferroptosis. DMT1 inhibitors selectively target CSC in primary cancer cells and circulating tumor cells, demonstrating the physiological relevance of this strategy. Taken together, this opens up opportunities to tackle unmet needs in anti-cancer therapy.     

Photoelectrochemical study of La2NiO4 synthesized using citrate sol gel method—application for hydrogen photo-production

Journal of Solid State Electrochemistry - The semi conducting properties of La2NiO4 synthesized through sol gel method are studied for the first time using photoelectrochemistry. The X-ray...     

Discrete semi-stable distributions

The purpose of this paper is to introduce and study the concepts of discrete semi-stability and geometric semi-stability for distributions with support inZ ₊. We offer several properties, including characterizations, of discrete semi-stable distributions. We establish that these distributions posses the property of infinite divisibility and that their probability generating functions admit canonical representations that are analogous to those of their continuous counterparts. Properties of discrete geometric semi-stable distributions are deduced from the results obtained for discrete semi-stability. Several limit theorems are established and some examples are constructed.     

Preparation and characterization of the system NiMn2O4/TiO2 by sol–gel: application to the photodegradation of benzamide under visible light

Journal of Sol-Gel Science and Technology - Benzamide is successfully degraded on the novel heterosystem NiMn2O4/TiO2 under visible light. The nanosized spinel is synthesized by the sol–gel...     

The finite capacity multi-server queue with inhomogeneous arrival rate and discrete service time distribution — and its application to continuous service time problems

The finite capacity multi-server queueing model with inhomogeneous arrival rate and discrete service time distribution is developed. The system is formulated as an inhomogeneous Markov chain in discrete time. An algorithm is described to solve the model numerically. A method is then proposed for using this model to approximate the time dependent behaviour of multi-server queues with inhomogeneous arrival rate and continuous service time distribution. Empirical results are presented to show that this approximation will produce results that are accurate enough for most practical purposes.     

A combinatorial method for solution-phase synthesis of labeled bivalent beta-turn mimics

Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure 1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key features of these molecules include (i) the possibility of incorporating amino acid side chains corresponding to many of the protein amino acids; (ii) a close correspondence of separations of these side chains to i + 1 to i + 2 residues in turns; (iii) facile adjustment of the side-chain vectors on docking while only influencing two critical degrees of freedom; and (iv) some electrostatic polarity. Fifteen monomers of this type were made via copper-mediated cycloaddition reactions. Solution-phase methodologies were devised to assemble these monomers into bivalent compounds in high purity states (typically >85%) so that they could be used in first-pass biological assays without further purification. The skeleton for forming these bivalent compounds is triazine-based. There is a third site which allowed for introduction of a fluorescent label (library of compounds 2) or an alkyne-functionalized triethylene glycol chain (library of compounds 3) included to promote water-solubility and to allow incorporation of probes via copper-mediated cycloaddition reactions. In the event, two 135-membered libraries were prepared, one consisting of compounds 2 and the other of 3. No protecting groups or coupling agents were required; these attributes of the method were important to allow most of the products to be obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was screened in a fluorescence-activated cell sorting (FACS) assay using cells transfected to overexpress one of the following neurotrophin receptors: TrkA, TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and 2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine turn mimic. Thus, a pharmacological probe for the TrkA receptor has been developed.     

Warehouse location with production,inventory, and distribution decisions: a case study in the lube oil industry

In this paper, a supply chain management problem from a real case study is modeled and solved. A company in Pakistan wanted to outsource part of its warehousing activity to a third party logistics (3PL) provider. Consequently, the company had to decide on where to rent space in the 3PL warehouses. Knowing that such a strategic decision is affected by tactical and operational decisions, the problem is presented as a facility location problem integrating production, inventory, and distribution decisions. The problem is formulated as a mixed integer linear programming model which minimizes the total cost composed of location, distribution, production, and inventory costs. Several constraints specific to the situation and policy of the company were considered. A thorough analysis was done on the results obtained with respect to formulation efficiency, sensitivity analysis, and distribution of costs. In addition to the solution of the company problem, a set of 1215 problem instances was generated by varying five types of relevant costs in a full factorial manner. The solution of the generated problems always suggests to open in the same two locations and the integrality gaps averaged 0.062 % with a maximum of 0.102 %. On average, the major components of the total cost are production cost (96.6 %), transportation costs (2.7 %), and inventory holding costs (0.38 %). The total warehouse opening cost accounted for less than 0.05 % of the total costs.     

Electrochemical intercalation of O2− in CuAlO2 single crystal and photoelectrochemical properties

The delafossite CuAlO₂ single crystal, prepared by the flux method, is a low mobility p-type semiconductor with a hole mobility of 1.2 × 10⁻⁵ cm⁻² V⁻¹ s⁻¹. The chronoamperometry showed an electrochemical O²⁻ insertion with a diffusion coefficient D _303K of 3.3 × 10⁻¹⁸ cm² s⁻¹. The thermal variation of D in the range 293–353 K gave an enthalpy of diffusion (ΔH) of 44.7 kJ mol⁻¹. CuAlO₂ is photoactive, and the Mott–Schottky plot indicates a flat band potential of +0.42 V vs saturated calomel electrode and a holes density (N _A) of 10¹⁶ cm⁻³. The photocurrent spectra have been analyzed by using the Gartner model from which the absorption coefficients and diffusion lengths were determined. An optical transition at 1.66 eV, indirectly allowed, has been obtained. The spectral photoresponse provides a high absorption at 480 nm. The low quantum yield (η) is attributed to a small depletion length (440 nm) and a hole diffusion width (271 nm) compared to a very large penetration depth (12 μm).