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

Density convergence in the Breuer-Major theorem for Gaussian stationary sequences

Consider a Gaussian stationary sequence with unit variance $X=\{X_k;k\in {\mathbb{N}}\cup\{0\}\}$. Assume that the central limit theorem holds for a weighted sum of the form $V_n=n^{-1/2}\sum^{n-1}_{k=0}f(X_k)$, where $f$ designates a finite sum of Hermite polynomials. Then we prove that the uniform convergence of the density of $V_n$ towards the standard Gaussian density also holds true, under a mild additional assumption involving the causal representation of $X$.Comment: Published at http://dx.doi.org/10.3150/14-BEJ646 in the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

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

Central limit theorem for an additive functional of the fractional Brownian motion

We prove a central limit theorem for an additive functional of the $d$-dimensional fractional Brownian motion with Hurst index $H\in(\frac{1}{1+d},\frac{1}{d})$, using the method of moments, extending the result by Papanicolaou, Stroock and Varadhan in the case of the standard Brownian motion.Comment: Published in at http://dx.doi.org/10.1214/12-AOP825 the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

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

Detection of recurrent cytogenetic aberrations in multiple myeloma: A comparison between MLPA and iFISH

Multiple myeloma (MM) is a genetically heterogeneous disease with diverse clinical characteristics and outcomes. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MM patients. In the present study, MLPA analysis was applied to analyze cytogenetics of CD138 tumor cells of 59 MM samples, and its result was compared, retrospectively, with the interphase fluorescence in situ hybridization (iFISH) data. We firstly established the normal range of each of the 42 diagnostic probes using healthy donor samples. A total of 151 aberrations were detected in 59 patient samples, and 49/59 cases (83.1%) harbored at least one copy number variation. Overall, 0–7 aberrations were detected per case using MLPA, indicating the heterogeneity and complexity of MM cytogenetics. We showed the high efficiency of MLPA and the high congruency of the two methods to assess cytogenetic aberrations. Considering that MLPA analysis is not reliable when the aberration only exits in a small population of tumor cells, it is essential to use both MLPA and iFISH as complementary techniques for the diagnosis of MM

Lymphangiogenesis Is Required for Pancreatic Islet Inflammation and Diabetes

Lymphangiogenesis is a common phenomenon observed during inflammation and engraftment of transplants, but its precise role in the immune response and underlying mechanisms of regulation remain poorly defined. Here we showed that in response to injury and autoimmunity, lymphangiogenesis occurred around islets and played a key role in the islet inflammation in mice. Vascular endothelial growth factors receptor 3 (VEGFR3) is specifically involved in lymphangiogenesis, and blockade of VEGFR3 potently inhibited lymphangiogenesis in both islets and the draining LN during multiple low-dose streptozotocin (MLDS) induced autoimmune insulitis, which resulted in less T cell infiltration, preservation of islets and prevention of the onset of diabetes. In addition to their well-known conduit function, lymphatic endothelial cells (LEC) also produced chemokines in response to inflammation. These LEC attracted two distinct CX3CR1hi and LYVE-1+ macrophage subsets to the inflamed islets and CX3CR1hi cells were influenced by LEC to differentiate into LYVE-1+ cells closely associated with lymphatic vessels. These observations indicate a linkage among lymphangiogenesis and myeloid cell inflammation during insulitis. Thus, inhibition of lymphangiogenesis holds potential for treating insulitis and autoimmune diabetes

Modélisation et commande d'un banc d'essai électro-hydraulique haute performance

Hydraulic systems are widely applied in industry for position or force control. However, due to hydraulic system nonlinearities, it is difficult to achieve a precise model valid over a large range of frequencies and movements. The work in this dissertation focuses on a high performance hydraulic test bench which involves three main hydraulic components, i.e. two high performance servovalves, a double rod actuator, and a specific intermediate block connecting the servovalves and actuator. This rig has been designed for testing aerospace or automotive components in real conditions (e.g. wear and ageing effects). The main objectives of this dissertation are first the development of a virtual prototype based on a precise model which is derived from the physical principles and experimental works, and then second the synthesis of several nonlinear control laws of this actuation system in a large operating range with a good robustness to the perturbations. The proposed model based on Bond Graph shows a very good agreement with experimental results not only at low frequencies, but also at high frequencies. Moreover, its performances are improved at high frequencies by introducing the dynamic effects due to the intermediate block. Besides, multivariable and monovariable control strategies, based on respectively the backstepping and the model-free method, are developed and implemented on the test bench. All the control strategies proposed have been validated by simulations and experiments. Results show they lead to better tracking precision and robustness performance compared to the conventional control techniques.Les systèmes électro-hydrauliques sont largement utilisés dans l’industrie pour des contrôles de position ou d’effort. Cependant, à cause des non-linéarités du système électro-hydraulique, il est difficile d’établir un modèle précis valable sur une large bande de fréquences et de grands mouvements. Le travail de cette thèse concerne un banc d’essai électro-hydraulique qui comporte trois composants hydrauliques principaux, à savoir deux servovalves haute performance, un vérin à double tige, et une embase spécifique qui relie les servovalves et le vérin. Ce banc d’essai a été conçu pour tester des composants aéronautique et automobile dans des conditions réelles (par exemple, tests d'usure ou de vieillissement). Le premier objectif principal de cette thèse concerne la mise en œuvre d’un prototype virtuel basé sur un modèle précis issu de considérations physiques et d'un travail expérimental afin d'identifier les paramètres et de valider le réalisme du prototype virtuel. Le deuxième objectif est d'élaborer des lois de commande non-linéaires sophistiquées avec une large plage de fonctionnement et une bonne robustesse aux perturbations. Le modèle proposé basé sur le Bond Graph montre une très bonne adéquation entre les résultats de simulation et les résultats expérimentaux non seulement en basses fréquences, mais également en fréquences élevées. En particulier, les performances en hautes fréquences sont nettement améliorées par l'introduction des effets dynamiques liés à l’embase. En outre, des lois de commande, respectivement basées sur le backstepping et sur la commande sans modèle, ont été élaborées et mises en œuvre sur le banc d’essai. Toutes les lois de commande proposées ont été validées à la fois en simulation et expérimentalement. Les résultats montrent qu’ils conduisent à de meilleures performances en suivi de position et en robustesse par rapport aux lois de commande classiques

Bond Graph model of the intermediate block in a hydraulic control system

International audienceThe intermediate block, as a basic element in the hydraulic control system, is used to install all hydraulic components and guides the fluid flows. The effect of this block, usually neglected, is taken into consideration in this paper since it is a part of a system developed for high performance applications and especially high frequencies [7]. By means of the Bond Graph tool, a detailed model is established. This model could then be easily integrated into the Bond Graph model of the whole system. Besides, the relationship between flow rates and pressure drops along with the energy losses in the block are obtained according to a method based on the decomposition of the circuit in parts for which the local losses can be obtained from abacuses. The computational fluid dynamics (CFD) is used for the validation of the results