UVA Assisted 4-Thiothymidine for Cancer Treatment

This article reviews the developments of 4-thiothymidine analogues, assisted with UVA light, as a novel cancer therapy. First, the key points on synthetic chemistry, photochemistry and cellular toxicity of 4-thiothymidine are summarized. As the chemical structure of 4-thiothymidine is very similar to that of its parent thymidine, thus 4-thiothymidine can be readily incorporated into cellular DNA, and with the help of thymidine kinase, much more preferably into cancerous DNA. Unlike thymidine, 4-thiothymdine can absorb strongly in UVA (longer wavelengths of UV) light. Thus UVA-assisted 4-thiothymidine offers an effective cancer treatment. Some underlying mechanisms of action by 4-thiothymidine/UVA and compares this cancer approach with the commonly used photodynamic therapy are discussed. The various interactions between 4-thiothymidine with human serum albumin are introduced. Finally, a short conclusion on the past efforts and a brief prospect for future work in this exciting research field are given

Synthesis of 4-thio-5-(2′′-thienyl)uridine and cytotoxicity activity against colon cancer cells <i>in vitro</i>

A novel anti-tumor agent 4-thio-5-(2′′-thienyl)uridine (6) was synthesized and the in vitro cytotoxicity activity against mice colon cancer cells (MC-38) and human colon cancer cells (HT-29) was evaluated by MTT assay. The results showed that the novel compound had antiproliferative activity toward MC-38 and HT-29 cells in a dose-dependent manner. The cell cycle analysis by flow cytometry indicated that compound 6 exerted in tumor cell proliferation inhibition by arresting HT-29 cells in the G2/M phase. In addition, cell death detected by propidium iodide staining showed that compound 6 efficiently induced cell apoptosis in a concentration-dependent manner. Moreover, the sensitivity of human fibroblast cells to compound 6 was far lower than that of tumor cells, suggesting the specific anti-tumor effect of 4-thio-5-(2′′-thienyl)uridine. Taken together, novel compound 6 effectively inhibits colon cancer cell proliferation, and hence would have potential value in clinical application as an antitumor agent

A distributionally robust index tracking model with the CVaR penalty: tractable reformulation

We propose a distributionally robust index tracking model with the conditional value-at-risk (CVaR) penalty. The model combines the idea of distributionally robust optimization for data uncertainty and the CVaR penalty to avoid large tracking errors. The probability ambiguity is described through a confidence region based on the first-order and second-order moments of the random vector involved. We reformulate the model in the form of a min-max-min optimization into an equivalent nonsmooth minimization problem. We further give an approximate discretization scheme of the possible continuous random vector of the nonsmooth minimization problem, whose objective function involves the maximum of numerous but finite nonsmooth functions. The convergence of the discretization scheme to the equivalent nonsmooth reformulation is shown under mild conditions. A smoothing projected gradient (SPG) method is employed to solve the discretization scheme. Any accumulation point is shown to be a global minimizer of the discretization scheme. Numerical results on the NASDAQ index dataset from January 2008 to July 2023 demonstrate the effectiveness of our proposed model and the efficiency of the SPG method, compared with several state-of-the-art models and corresponding methods for solving them

Stabilizing Q Learning Via Soft Mellowmax Operator

Learning complicated value functions in high dimensional state space by function approximation is a challenging task, partially due to that the max-operator used in temporal difference updates can theoretically cause instability for most linear or non-linear approximation schemes. Mellowmax is a recently proposed differentiable and non-expansion softmax operator that allows a convergent behavior in learning and planning. Unfortunately, the performance bound for the fixed point it converges to remains unclear, and in practice, its parameter is sensitive to various domains and has to be tuned case by case. Finally, the Mellowmax operator may suffer from oversmoothing as it ignores the probability being taken for each action when aggregating them. In this paper, we address all the above issues with an enhanced Mellowmax operator, named SM2 (Soft Mellowmax). Particularly, the proposed operator is reliable, easy to implement, and has provable performance guarantee, while preserving all the advantages of Mellowmax. Furthermore, we show that our SM2 operator can be applied to the challenging multi-agent reinforcement learning scenarios, leading to stable value function approximation and state of the art performance.Comment: 14 page

Consumer attitude towards sustainability of fast fashion products in the UK

This paper attempts to provide an up-to-date depiction and analysis of the consumer’s attitude towards sustainability of fast fashion products in the UK. Four related strands of literature are reviewed to establish a tri-component model of attitude (ABC), i.e., Affective, Behavioural and Cognitive. A wide set of determinants for attitude is identified, including income, price, gender, culture, religion, age, etc. Based on this conceptual framework, an online questionnaire is designed and sent to university students and alumni in the UK, returning 128 valid responses. Both descriptive statistics and regression analysis (oprobit) are employed to shed light on the three components of attitude towards sustainability. It is found that cognitive and behavioural components converge across cultures and religions, but the affective component remains significantly diverse. Employment status contributes to the awareness, decision and feeling of sustainability features, but gender only matters for purchase decisions. In general, there is an improved cognitive and affective awareness of sustainability, but this does not automatically translate to purchase behaviour. Policy interventions like taxes and subsidies are still needed to foster sustainability in the fast fashion industry

A one-dimensional extremely covalent material: monatomic carbon linear chain

Polyyne and cumulene of infinite length as the typical covalent one-dimensional (1D) monatomic linear chains of carbon have been demonstrated to be metallic and semiconductor (Eg = 1.859 eV), respectively, by first-principles calculations. Comparing with single-walled carbon nanotubes, the densities are evidently low and the thermodynamic properties are similar below room temperature but much different at the high temperature range. Polyyne possesses a Young's modulus as high as 1.304 TPa, which means it is even much stiffer than carbon nanotubes and to be the superlative strong 1D material along the axial direction. The Young's modulus of cumulene is estimated to be 760.78 GPa. In addition, polyyne is predicted to be as a one-dimensional electronic material with very high mobility

The Synthesis of (E)-4-Thio-5-(2-Bromovinyl)Uridine/Deoxyuridine and Its Characterization and Cytotoxicity

(E)-4-Thio-5-(2-brominevinyl)uridine/2'-deoxyuridine(8a/8b) were efficiently and in an environmental friendly way synthesized from uridine/2'-deoxyuridine (1a/1b) that were first transformed to (E)-(2-brominevinyl) uridine / 2'-deoxyuridine(5a/5b) via iodination, selective oxidation, Heck reaction steps. The resulting products (5a/5b) were then converted to the targets (8a/8b) through esterification, thio-reaction of carbonyl, hydrolysis steps. Two new compounds (8a/8b) and three new intermediates (7a 7b 10) were obtained, and their structures have been fully characterized by 1H NMR, 13C NMR, IR, UV, HR-MS, X-Ray. The study of 8a and their derivatives regarding cytotoxicity was carried out by using MTT experiment method, and the initial findings suggest (E)-4-Thio-5-(2-brominevinyl) uridine/ 2'-deoxyuridine (8a / 8b) would be potential antitumor drugs