Design, synthesis, and biological activities of small molecules that target myotonic dystrophy

Myotonic dystrophy (DM) is a triple-repeat expansion, multi-systemic disease that affects one in eight thousand people worldwide. The cause of the disease is a progressive, abnormal expansion of CTG repeats (CUGexp) in the 3'-UTR of the DMPK gene (DM1) and CCTG repeats (CCUGexp) in the intron 1 of the ZNP9 gene (DM2). The sequestration of muscleblind-like proteins (MBNL) by CUGexp or CCUGexp causes splicing defects in more than 100 pre-mRNAs, resulting in various disease phenotypes. As such, therapeutic development for DM has mainly focused on agents targeting the CUGexp/CCUGexp -MBNL1 interaction. This dissertation focuses on the development of rationally designed small molecules that target CUGexp and CCUGexp, including their synthesis and studies of their biological activity. The background of DM with a focus on its molecular mechanism and various therapeutic approaches are reviewed in Chapter 1. Chapter 2 includes the story of how simple ligands targeting CUGexp have been developed and investigations of the biological activity of acridine-based and bisamidinium-based ligands synthesized by others in our group. Chapter 3 focuses on the design, synthesis, and biological activity of bisamidinium-based ligands that target CCUGexp. Because other toxic pathways, including microRNA dysregulation in DM1 heart tissue and the production of polypeptides via repeat-associated non-ATG translation, are induced by CUGexp, recent efforts on DM1 therapeutic approaches have moved beyond just preventing the formation of CUGexp-MBNL1 complex and further focused on regulating the level of toxic CUGexp. Thus, Chapter 4 discusses a multi-target approach for DM1 in which a ligand with a RNA-cleaving unit can bind both CTGexp and CUGexp and regulate the level of CUGexp

Online Load Balancing for Network Functions Virtualization

Network Functions Virtualization (NFV) aims to support service providers to deploy various services in a more agile and cost-effective way. However, the softwarization and cloudification of network functions can result in severe congestion and low network performance. In this paper, we propose a solution to address this issue. We analyze and solve the online load balancing problem using multipath routing in NFV to optimize network performance in response to the dynamic changes of user demands. In particular, we first formulate the optimization problem of load balancing as a mixed integer linear program for achieving the optimal solution. We then develop the ORBIT algorithm that solves the online load balancing problem. The performance guarantee of ORBIT is analytically proved in comparison with the optimal offline solution. The experiment results on real-world datasets show that ORBIT performs very well for distributing traffic of each service demand across multipaths without knowledge of future demands, especially under high-load conditions

Development of a diagnostic scar marker for Vibrio shilonii caused acute hepatopancreatic necrosis disease in whiteleg shrimp

Background: In a previous report, we showed that Vibrio shilonii was found on whiteleg shrimp (Litopenaeus vannamei) with acute hepatopancreatic necrosis disease in Thua Thien Hue province, Vietnam. This study was performed to develop a diagnostic molecular marker generated by random amplified polymorphic DNA (RAPD) for V. shilonii rapid detection.Methods: Pathogen Vibrio spp. were isolated from shrimps and fishes, and were identified by 16S rRNA sequencing. Genetic diversity of Vibrio strains was analysis by RAPD technique. Specific PCR product for V. shilonii was cloned and sequenced. SCAR marker was developed from specific PCR product.Result: Twenty random primers were evaluated for RAPD to identify DNA polymorphisms between Vibrio species. The random primer OPN-06 generated a 468-bp DNA fragment specific for V. shilonii. This was then converted into a sequence-characterized amplified region (SCAR) marker designated N6-441.Conclusion: Specific primers (Vshi-441F/Vshi-441R) amplified a unique DNA fragment in all V. shilonii isolates but not in the other Vibrio spp. This PCR assay showed significantly sensitive to the target DNA and reliably for the amplification the V. shilonii genome.Keywords: AHPND; RAPD; SCAR; Vibrio shilonii; Vietna

Calculation of Temperature-Dependent Thermal Expansion Coefficient of Metal Crystals Based on Anharmonic Correlated Debye Model

This study aims to calculate the anharmonic thermal expansion (TE) coefficient of metal crystals in the temperature dependence. The calculation model is derived from the anharmonic correlated Debye (ACD) model that is developed using the many-body perturbation approach and correlated Debye model based on the anharmonic effective potential. This potential has taken into account the influence on the absorbing and backscattering atoms of all their nearest neighbors in the crystal lattice. The numerical results for the crystalline zinc (Zn) and crystalline copper (Cu) are in agreement with those obtained by the other theoretical model and experiments at several temperatures. The analytical results show that the ACD model is useful and efficient in analyzing the TE of coefficient of metal crystals

Optimization of spray-drying conditions and quality assessment of dry extract from Perilla frutescens (L.) Britton leaves

Context: Perilla frutescens and its dried extract have been employed in food and pharmaceutical manufacturing due to the plant's biological activities, which include antibacterial, anti-allergic, anticancer, antiviral, antioxidant, and antidepressant properties. Despite numerous studies on preparing dry extracts from various medicinal herbs, no research has been conducted to optimize spray-drying conditions specifically for P. frutescens. Aims: To optimize the spray-drying parameters using BCPharSoft software and evaluate the quality of P. frutescens dry extract. Methods: D-optimal design based on four independent variables carrier type (Glucidex, Glucidex: Arabic gum 9:1, Glucidex: Arabic gum 8:2), carrier mass (10, 15, and 20 g), inlet air temperature (160, and 180℃) and flow rate (12, and 14 rpm/min) was applied to investigate the cause-effect relations and optimized preparation process. The drying performance, moisture content, total phenol, and total flavonoid content were investigated as four dependent variables. Results: All independent variables had significant effects on the dependent variables. The optimal parameters of the preparation process included using carrier Glucidex: Arabic gum at a ratio of 9:1, carrier mass of 19 g, inlet air temperature of 161°C, and flow rate of 12 rpm/min. The drying performance, moisture content, total phenol, and flavonoid content of the optimized P. frutescens dry extract were found to be 10.42%, 4.80%, and 90.57 mg GA/g, and 53.55 mg QE/g, respectively. Conclusions: Dried P. frutescens extract has been efficiently produced using the spray-drying technique, establishing a foundation for future manufacturing of pharmaceuticals and functional foods derived from P. frutescens

SYNTHESIS, CHARACTERIZATION AND ELECTROCHEMICAL PERFORMANCE OF ACTIVATED CARBON SUPPORTED MnO2 FOR ELECTROCHEMICAL CAPACITOR

MnO2 was synthesized by adding activated carbon into KMnO4 solution and stirred in a magnetic or ultrasonic stirrer. The obtained MnAC samples were characterized by means of XRD, TGA, TPR-H2, SEM and BET. All samples are amorphous and have porous structure. MnAC-M prepared by magnetic stirring have higher manganese content, earlier reduction temperature, smoother surface area while MnAC-U prepared by ultrasonic stirring have larger specific surface area and pore volume

Phenolic compounds from leaves of Amensiodendron chinese (Sapindaceae)

From the ethyl acetate extract of the leaves of Amensiodendron chinense (Merr.) Hu (Sapindaceae), we isolated three known phenolic compounds: 4-hydroxy-3-methoxybenzaldehyde (1), methyl 3,4-dihydroxybenzoate (2), and 3,4-dihydroxybenzoic acid (3). We elucidated their chemical structures from the spectral data and compared them with those reported in the literature.3 hợp chất phenolic được phân lập từ cao chiết ethyl acetate của lá thuộc loài Amensiodendron chinese (Merr.) Hu (Sapindaceae) bao gồm : 4-hydroxy-3-methoxybenzaldehyde (1), methyl 3,4-dihydroxybenzoate (2), 3,4-dihydroxybenzoic acid (3). Cấu trúc hóa học được xác định dựa vào dữ liệu phổ và so sánh với tài liệu tham khảo

Synthesis and Optical Characterization of Dye Doped in Ormosil Nanospheres for Bioapplications

Dye-doped ORMOSIL (organically modified silicate) nanoparticles (NPs) have significant advantages over single-dye labeling in signal amplification, photostability and surface modification for various biological applications. The dyes: Rhodamine 6G (R6G) and Rhodamine B (RB) were successfully incorporated into ORMOSIL nanoparticles fabricated by micellar nanochemistry from Trimethoxysilane CH$_3$Si(OCH$_3$)$_3$ precursor. The optical characterization of dye-doped ORMOSIL NPs was studied in comparison with it’s of free dye in solution. The results shown that the photostability of ORMOSIL dye doped nanospheres is much improved in comparison with it’s of dye in solution. Other studies of the photophysical properties such as anisotropy, fluorescence lifetime and energy transfer were also done

Feature selection methods and sampling techniques to financial distress prediction for Vietnamese listed companies

The research is taken to integrate the effects of variable selection approaches, as well as sampling techniques, to the performance of a model to predict the financial distress for companies whose stocks are traded on securities exchanges of Vietnam. A firm is financially distressed when its stocks are delisted as requirement from Vietnam Stock Exchange because of making a loss in 3 consecutive years or having accumulated a loss greater than the company’s equity. There are 12 models, constructed differently in feature selection methods, sampling techniques, and classifiers. The feature selection methods are factor analysis and F-score selection, while 3 sets of data samples are chosen by choice-based method with different percentages of financially distressed firms. In terms of classifying technique, logistic regression together with SVM are used in these models. Data are collected from listed firms in Vietnam from 2009 to 2017 for 1, 2 and 3 years before the announcement of their delisting requirement. The experiment’s results highlight the outperformance of the SVM model with F-score selection method in a data sample containing the highest percentage of non-financially distressed firms